V.V.U na Upimaji wake (Coincidences)

[Abou Saydou]

Pole sana everlenk

Inasikitisha sana nimesoma mpaka nahisi maumivu daaah tunaangamia.

 

[everlenk]

Pole sana everlenk

Inasikitisha sana nimesoma mpaka nahisi maumivu daaah tunaangamia.

Asante sana Mkuu,ndo vile tena tunaomba Mungu tu atusaidie, Mkuu usiombe the so called Aids/HIV liingie kwenye familia yako inatisha sana aiseee!!!! Linarudisha maendeleo nyuma si mchezo maana Hamna kutulia kila siku ni kuhangaika tu, yaani katika miezi hii miwili takriban 8M zimekatika na bado ndo kama hivi yupo hospital tena, somehow imeshake nguvu kazi yangu maana tumekosa kusimamia kazi zetu moja kwa moja tunahangaika na mgonjwa tu,katika miezi hii miwili nimeingia ofisini kwangu mara Nne tu, inabidi nikae na mgonjwa maana huduma zake si mchezo kwa mtu ambaye si wa karibu naye na mwenye moyo hawezi Fanya.

 

[Kobe]

Ila we jamaa Deception hoja zako zinamashiko usije tufanya watu tukapiga kavukavu

Dah aisee hapa ni noma jamaa anaweza kutumbukiza wengi ila tuendelee kumsoma kuna maana fulani ipo hapa.

 

[Kobe]

Unajua mkuu,walioanzisha nadharia ya HIV/AIDS wanajua wazi mikanganyiko iliyopo kuhusu dhana hii,ndio maana wanakuna vichwa kutunga nadharia nyingine za uongo ili kurubuni akili za watu na kuwafanya wasiwe na mashaka na suala zima la HIV/AIDS.Mifano;

1.Watu waliopima HIV+ kwa miaka mingi sana lakini hawaugui hata kama hawatumii ARVs huitwa CARRIERS.

2.Wanandoa wanaoishi pamoja muda mrefu lakini mmoja ni HIV+ lakini mwingine ni HIV- huitwa DISCORDANT COUPLES.

3.Baada ya kuona watu wenye huyo HIV wanaugua kwa viwango na kasi tofauti katika maeneo tofauti duniani wakaja na nadharia ya HIV-1 na HIV-2.

SWALI:
Je,mimi niliyejidunga damu ya mtu alipima HIV+ na baada ya muda mrefu nilipima HIV- watatumia nadharia gani kujibu huu mkanganyiko?Inabidi tuwaite WHO waje Tanzania kunifanyia uchunguzi.Ha ha haaa,kweli knowledge is power.

we jamaa ni noma umeileta JF ya miaka ilee tulikuwa tunapata mada kama hizi full nondo..Big up sana.

 

[pakamwam]

acha kudanganya watu wewe. ukiendelea hivi unaweza kuwa mpiga ramli

 

[pakamwam]

umeongea mambo mengi sana ambayo mimi kama mwalimu wa chuocha afya fulani nashindwa nianzie wapi. cha msingi kama kweli unahitaji kujua nitafute kwa simu ambayo nitakupm. nitakuelewesha kwa kirefu.

pia katika vipimo tuna vitu vitu vingi, tuna antigen/antibody based tests, tuna polymerase chain reaction tests na test nyingine nyingi. the gold standard katika test zote zote ni PCR tests ambazo zinaweza kumwona mdudu kama mdudu kwa kutumia vinasaba.
yapo mamb mengi ya kukuelimisha kuhusu vipimo. nitafute kwenye namba hiyo au karibu in vitro maabara mbezi ya kimara. tutakuelimisha bure na kukupa ushauri bure kuhusu afya kwa ujumla wake

 

[Abou Saydou]

acha kudanganya watu wewe. ukiendelea hivi unaweza kuwa mpiga ramli

Onesha wapi anadanganya na sio maneno matupu tu .

 

[Kobe]

umeongea mambo mengi sana ambayo mimi kama mwalimu wa chuocha afya fulani nashindwa nianzie wapi. cha msingi kama kweli unahitaji kujua nitafute kwa simu ambayo nitakupm. nitakuelewesha kwa kirefu.

pia katika vipimo tuna vitu vitu vingi, tuna antigen/antibody based tests, tuna polymerase chain reaction tests na test nyingine nyingi. the gold standard katika test zote zote ni PCR tests ambazo zinaweza kumwona mdudu kama mdudu kwa kutumia vinasaba.
yapo mamb mengi ya kukuelimisha kuhusu vipimo. nitafute kwenye namba hiyo au karibu in vitro maabara mbezi ya kimara. tutakuelimisha bure na kukupa ushauri bure kuhusu afya kwa ujumla wake

pakaman tupo wengi sana tunahitaji hii elimu lakini hatupo dar es salaam hivyo ingekuwa bora zaidi umwage data au ushauri wako hapa jukwaani tuelimike sote

 

[pakamwam]

yote ulioyandika ni uongo. mimi ni mwalimu wa chuo cha muhimbili kwenye sayansi za maabara. HIV ipo, unaweza kuisolate hata wewe ukifundishwa na pia vipimovyote ni kweli na sio imani. asikudanganye mtu na hizo articles unazosoma na za medical fanatics na fallacy. jaribu kusoma articles toka HINARI, PUBMED na WHO utapa articles zenye ukweli na in depth knowledge

 

[pakamwam]

​​

[TABLE="width: 100%"] [TR] [TD="align: center"]

[TD="bgcolor: #ffffff"]HIV in humans originated from cross-species infections by simian viruses in rural Africa, probably due to direct human contact with infected primate blood. Current evidence is that the primate counterparts of HIV-1 and HIV-2 were transmitted to humans on multiple (at least seven) different occasions. Sequence evolution analyses place the introduction of SIV[SUB]cpz[/SUB] into humans that gave rise to HIV-1 group M at about 1930. Presumably, such transmissions occurred repeatedly over the ages, but particular social, economic, and behavioral changes that occurred in the mid 20th century provided circumstances that allowed these virus infections to expand, become well-established in humans, and reach epidemic proportions.
Disinfection & Inactivation
HIV is completely inactivated (

10[SUP]5[/SUP] units of infectivity) by treatment for 10 minutes at room temperature with any of the following: 10% household bleach, 50% ethanol, 35% isopropanol, 1% Nonidet P40, 0.5% Lysol, 0.5% paraformaldehyde, or 0.3% hydrogen peroxide. The virus is also inactivated by extremes of pH (pH 1.0, pH 13.0). However, when HIV is present in clotted or unclotted blood in a needle or syringe, exposure to undiluted bleach for at least 30 seconds is necessary for inactivation.
The virus is not inactivated by 2.5% Tween 20. Although paraformaldehyde inactivates virus free in solution, it is not known if it penetrates tissues sufficiently to inactivate all virus that might be present in cultured cells or tissue specimens.
HIV is readily inactivated in liquids or 10% serum by heating at 56 °C for 10 minutes, but dried proteinaceous material affords marked protection. Lyophilized blood products would need to be heated at 68 °C for 72 hours to ensure inactivation of contaminating virus.
Animal Lentivirus Systems
Insights into the biologic characteristics of lentivirus infections have been gained from experimental infections, including sheep with visna virus (Table 44–2). Natural disease patterns vary among species, but certain common features are recognized.
(1) Viruses are transmitted by exchange of body fluids.
(2) Virus persists indefinitely in infected hosts, though it may be present at very low levels.
(3) Viruses have high mutation rates, and different mutants will be selected under different conditions (host factors, immune responses, tissue types). Infected hosts contain "swarms" of closely related viral genomes, known as quasi species.
(4) Virus infection progresses slowly through specific stages. Cells in the macrophage lineage play central roles in the infection. Lentiviruses differ from other retroviruses in that they can infect nondividing, terminally differentiated cells. However, those cells must be activated before viral replication ensues and progeny virus is produced. Virus is cell-associated in monocytes and macrophages, but only about one cell per million is infected. Monocytes carry the virus around the body in a form that the immune system cannot recognize, seeding other tissues. Lymphocyte-tropic strains of virus tend to cause highly productive infections, whereas replication of macrophage-tropic virus is restricted.
(5) It may take years for disease to develop. Infected hosts usually make antibodies, but they do not clear the infection, so virus persists lifelong. New antigenic variants periodically arise in infected hosts, with most mutations occurring in envelope glycoproteins. Clinical symptoms may develop at any time from 3 months to many years after infection. The exceptions to long incubation periods for lentivirus disease include AIDS in children, infectious anemia in horses, and encephalitis in young goats.
Host factors important in pathogenesis of disease include age (the young are at greater risk), stress (may trigger disease), genetics (certain breeds of animals are more susceptible), and concurrent infections (may exacerbate disease or facilitate virus transmission).
The diseases in ungulates (horses, cattle, sheep, and goats) are not complicated by opportunistic secondary infections. Equine infectious anemia virus can be spread among horses by blood-sucking horseflies, the only lentivirus known to be transmitted by an insect vector.
Simian lentiviruses share molecular and biologic characteristics with HIV and cause an AIDS-like disease in rhesus macaques. The SIV model is important for understanding disease pathogenesis and developing vaccine and treatment strategies.
Virus Receptors
All primate lentiviruses use as a receptor the CD4 molecule, which is expressed on macrophages and T lymphocytes. A second coreceptor in addition to CD4 is necessary for HIV-1 to gain entry to cells. The second receptor is required for fusion of the virus with the cell membrane (Figure 44–4). The virus first binds to CD4 and then to the coreceptor. These interactions cause conformational changes in the viral envelope, activating the gp41 fusion peptide and triggering membrane fusion. Chemokine receptors serve as HIV-1 second receptors. (Chemokines are soluble factors with chemoattractant and cytokine properties.) CCR5, the receptor for chemokines RANTES, MIP-1

, and MIP-1

, is the predominant coreceptor for macrophage-tropic strains of HIV-1, whereas CXCR4, the receptor for chemokine SDF-1, is the coreceptor for lymphocyte-tropic strains of HIV-1. The chemokine receptors used by HIV for cell entry are found on lymphocytes, macrophages, and thymocytes as well as on neurons and cells in the colon and cervix. Individuals who possess homozygous deletions in CCR5 and produce mutant forms of the protein may be protected from infection by HIV-1; mutations in the CCR5 gene promoter appear to delay disease progression. The requirement for a coreceptor for HIV fusion with cells provided new targets for antiviral therapeutic strategies, with the first HIV entry inhibitor licensed in the United States in 2003.

[TABLE="width: 100%"] [TR] [TD]Figure 44–4.

[/TD]

[TD="class: font11"]HIV fusion with target cell. Gp120 binds to the CD4 molecule and then to the coreceptor (CCR5 or CXCR4). This causes a conformational change in the viral envelope proteins, affecting gp41 so that the fusion peptide penetrates the cell and leads to membrane fusion.
(Reproduced, with permission, from Binley J, Moore JP: The viral mousetrap. Nature 1997;387:346.)
[/TD]

[/TD]
[/TR]
[/TABLE]
A dendritic cell-specific lectin, DC-SIGN, appears to bind HIV-1 but not to mediate cell entry. Rather, it may facilitate transport of HIV by dendritic cells to lymphoid organs and enhance infection of T cells.
[/TD]
[/TR]
[/TABLE]

[TABLE="width: 100%"] [TR] [TD="align: center"]

[TD="bgcolor: #ffffff"]HIV Infections in Humans
Pathogenesis & Pathology
Overview of Course of HIV Infection
The typical course of untreated HIV infection spans about a decade (Figure 44–5). Stages include the primary infection, dissemination of virus to lymphoid organs, clinical latency, elevated HIV expression, clinical disease, and death. The duration between primary infection and progression to clinical disease averages about 10 years. In untreated cases, death usually occurs within 2 years after the onset of clinical symptoms.

[TABLE="width: 100%"] [TR] [TD]Figure 44–5.

[/TD]

[TD="class: font11"]Typical course of untreated HIV infection. During the early period after primary infection, there is widespread dissemination of virus and a sharp decrease in the number of CD4 T cells in peripheral blood. An immune response to HIV ensues, with a decrease in detectable viremia followed by a prolonged period of clinical latency. Sensitive assays for viral RNA show that virus is present in the plasma at all times. The CD4 T cell count continues to decrease during the following years until it reaches a critical level below which there is a substantial risk of opportunistic diseases.
(Reproduced, with permission, from Pantaleo G, Graziosi C, Fauci AS: New concepts in the immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 1993;328:327.)
[/TD]

[/TD]
[/TR]
[/TABLE]
Following primary infection, there is a 4- to 11-day period between mucosal infection and initial viremia; the viremia is detectable for about 8–12 weeks. Virus is widely disseminated throughout the body during this time, and the lymphoid organs become seeded. An acute mononucleosis-like syndrome develops in many patients (50–75%) 3–6 weeks after primary infection. There is a significant drop in numbers of circulating CD4 T cells at this early time. An immune response to HIV occurs 1 week to 3 months after infection, plasma viremia drops, and levels of CD4 cells rebound. However, the immune response is unable to clear the infection completely, and HIV-infected cells persist in the lymph nodes.
This period of clinical latency may last for as long as 10 years. During this time, there is a high level of ongoing viral replication. It is estimated that 10 billion HIV particles are produced and destroyed each day. The half-life of the virus in plasma is about 6 hours, and the virus life cycle (from the time of infection of a cell to the production of new progeny that infect the next cell) averages 2.6 days. CD4 T lymphocytes, major targets responsible for virus production, appear to have similar high turnover rates. Once productively infected, the half-life of a CD4 lymphocyte is about 1.6 days. Because of this rapid viral proliferation and the inherent error rate of the HIV reverse transcriptase, it is estimated that every nucleotide of the HIV genome probably mutates on a daily basis.
Eventually, the patient will develop constitutional symptoms and clinically apparent disease, such as opportunistic infections or neoplasms. Higher levels of virus are readily detectable in the plasma during the advanced stages of infection. HIV found in patients with late-stage disease is usually much more virulent and cytopathic than the strains of virus found early in infection. Often, a shift from monocyte-tropic or macrophage-tropic (M-tropic) strains of HIV-1 to lymphocyte-tropic (T-tropic) variants accompanies progression to AIDS.
CD4 T Lymphocytes and Memory Cells
The cardinal feature of HIV infection is the depletion of T helper-inducer lymphocytes-the result of HIV replication in this population of lymphocytes as well as of the death of uninfected T cells by indirect mechanisms. The T cells express the CD4 phenotypic marker on their surface. The CD4 molecule is the major receptor for HIV; it has a high affinity for the viral envelope. The HIV coreceptor on lymphocytes is the CXCR4 chemokine receptor.
Early in infection, primary HIV isolates are M-tropic. However, all strains of HIV infect primary CD4 T lymphocytes (but not immortalized T cell lines in vitro). As the infection progresses, the dominant M-tropic viruses are replaced by T-tropic viruses. Laboratory adaptation of these primary isolates in immortalized T cell lines results in loss of ability to infect monocytes and macrophages.
The consequences of CD4 T cell dysfunction caused by HIV infection are devastating because the CD4 T lymphocyte plays a critical role in the human immune response. It is responsible directly or indirectly for induction of a wide array of lymphoid and nonlymphoid cell functions. These effects include activation of macrophages; induction of functions of cytotoxic T cells, natural killer cells, and B cells; and secretion of a variety of soluble factors that induce growth and differentiation of lymphoid cells and affect hematopoietic cells.
At any given time, only a small fraction of CD4 T cells are productively infected. Many infected T cells are killed, but a fraction survive and revert to a resting memory state. There is little or no virus gene expression in the memory cells, and they provide a long-term, stable latent reservoir for the virus. When exposed to antigen, the memory cells become activated and release infectious virus. The latent reservoir of infected memory cells decays very slowly, with a half-life of at least 43 months. It is unlikely that an HIV infection can be cured; if there were a million infected memory cells in the body, it would take about 70 years for them to decay.
Monocytes and Macrophages
Monocytes and macrophages play a major role in the dissemination and pathogenesis of HIV infection. Certain subsets of monocytes express the CD4 surface antigen and therefore bind to the envelope of HIV. The HIV coreceptor on monocytes and macrophages is the CCR5 chemokine receptor. In the brain, the major cell types infected with HIV appear to be the monocytes and macrophages, and this may have important consequences for the development of neuropsychiatric manifestations associated with HIV infection. Infected pulmonary alveolar macrophages may play a role in the interstitial pneumonitis seen in certain patients with AIDS.
Macrophage-tropic strains of HIV predominate early after infection, and these strains are responsible for initial infections even when the transmitting source contains both M-tropic and T-tropic viruses.
It is believed that monocytes and macrophages serve as major reservoirs for HIV in the body. Unlike the CD4 T lymphocyte, the monocyte is relatively refractory to the cytopathic effects of HIV, so that the virus not only can survive in this cell but can be transported to various organs in the body (such as the lungs and brain). Infected macrophages may continue to produce virus for a long period of time.
Lymphoid Organs
Lymphoid organs play a central role in HIV infection. Lymphocytes in the peripheral blood represent only about 2% of the total lymphocyte pool, the remainder being located chiefly in lymphoid organs. It is in the lymphoid organs that specific immune responses are generated. The network of follicular dendritic cells in the germinal centers of lymph nodes traps antigens and stimulates an immune response. Throughout the course of untreated infection-even during the stage of clinical latency-HIV is actively replicating in lymphoid tissues. The microenvironment of the lymph node is ideal for the establishment and spread of HIV infection. Cytokines are released, activating a large pool of CD4 T cells that are highly susceptible to HIV infection. As the late stages of HIV disease progress, the architecture of the lymph nodes becomes disrupted.
Neural Cells
Neurologic abnormalities are common in late stages of infection and are an AIDS-defining condition. Central nervous system disease occurs to varying degrees in 40–90% of patients. These include HIV encephalopathy, peripheral neuropathies, and-most serious-AIDS dementia complex. Both direct and indirect pathogenic mechanisms might explain the neuropsychiatric manifestations of HIV infection. The predominant cell types in the brain that are infected with HIV are monocytes and macrophages. Virus may enter the brain through infected monocytes and release cytokines that are toxic to neurons as well as chemotactic factors that lead to infiltration of the brain with inflammatory cells. HIV is present rarely, if at all, in neurons, oligodendrocytes, and astrocytes.
Viral Coinfections
Activation signals are required for the establishment of a productive HIV infection. In the HIV-infected individual, a wide range of in vivo antigenic stimuli seem to serve as cellular activators. For example, active infection by Mycobacterium tuberculosis substantially increases plasma viremia. Other concomitant viral infections-with EB virus, cytomegalovirus, herpes simplex virus, or hepatitis B virus-may serve as cofactors of AIDS. Hepatitis C virus coinfection, which occurs in 15–30% of HIV cases in the United States and often results in liver disease, is a leading cause of morbidity and mortality in HIV-infected persons. There is also a high prevalence of cytomegalovirus infection in HIV-positive individuals.
Coinfections with two different strains of HIV can occur. There are documented cases of superinfection with a second strain in an HIV-infected individual, even in the presence of a strong CD8 T cell response to the first strain. HIV superinfection is considered to be a rare event.
Clinical Findings
Symptoms of acute HIV infection are nonspecific and include fatigue, rash, headache, nausea, and night sweats. AIDS is characterized by pronounced suppression of the immune system and development of a wide variety of severe opportunistic infections or unusual neoplasms (especially Kaposi's sarcoma). The more serious symptoms in adults are often preceded by a prodrome ("diarrhea and dwindling") that can include fatigue, malaise, weight loss, fever, shortness of breath, chronic diarrhea, white patches on the tongue (hairy leukoplakia, oral candidiasis), and lymphadenopathy. Disease symptoms in the gastrointestinal tract from the esophagus to the colon are a major cause of debility. With no treatment, the interval between primary infection with HIV and the first appearance of clinical disease is usually long in adults, averaging about 8–10 years. Death occurs about 2 years later.
Plasma Viral Load
The amount of HIV in the blood (viral load) is of significant prognostic value. There are continual rounds of viral replication and cell killing in each patient, and the steady-state level of virus in the blood varies from individual to individual. This level reflects the total number of productively infected cells and their average burst size. It turns out that a single measurement of plasma viral load about 6 months after infection is able to predict the subsequent risk of development of AIDS in men several years later (Figure 44–6). However, more recent data suggest a gender difference in this parameter-in women, the viral load may be less predictive of progression to AIDS. Plasma HIV RNA levels can be determined using a variety of commercially available assays. The plasma viral load appears to be the best predictor of long-term clinical outcome, whereas CD4 lymphocyte counts are the best predictor of short-term risk of developing an opportunistic disease. Plasma viral load measurements are a critical element in assessing the effectiveness of antiretroviral drug therapy.

[TABLE="width: 100%"] [TR] [TD]Figure 44–6.

[/TD]
[/TR]
[TR]
[TD][TABLE="width: 100%"]
[TR]
[TD="align: center"]

[/TD]
[/TR]
[TR]
[TD="class: font11"]Prognostic value of HIV-1 RNA levels in the plasma (viral load). The virologic setpoint predicts the long-term clinical outcome.
(Reproduced, with permission, from Ho DD: Viral counts count in HIV infection. Science 1996;272:1124.)
[/TD]
[/TR]
[/TABLE]
[/TD]
[/TR]
[/TABLE]
Pediatric AIDS
The responses of infected neonates are different from those observed in HIV-infected adults. Pediatric AIDS-acquired from infected mothers-usually presents with clinical symptoms by 2 years of age; death follows in another 2 years. The neonate is particularly susceptible to the devastating effects of HIV because the immune system has not developed at the time of primary infection. Clinical findings may include lymphoid interstitial pneumonitis, pneumonia, severe oral candidiasis, encephalopathy, wasting, generalized lymphadenopathy, bacterial sepsis, hepatosplenomegaly, diarrhea, and growth retardation.
Children with perinatally acquired HIV-1 infection-if untreated-have a very poor prognosis. A high rate of disease progression occurs in the first few years of life. High levels of plasma HIV-1 load appear to predict infants at risk of rapid progression of disease. The pattern of viral replication in infants differs from that in adults. Viral RNA load levels are generally low at birth, suggesting infection acquired close to that time; RNA levels then rise rapidly within the first 2 months of life and are followed by a slow decline until the age of 24 months, suggesting that the immature immune system has difficulty containing the infection. A small percentage of infants (

5%) display transient HIV infections, suggesting that some infants can clear the virus.
Neurologic Disease
Neurologic dysfunction occurs frequently in HIV-infected persons. Forty to 90 percent of patients have neurologic symptoms, and many are found during autopsy to have neuropathologic abnormalities.
Several distinct neurologic syndromes that occur frequently include subacute encephalitis, vacuolar myelopathy, aseptic meningitis, and peripheral neuropathy. AIDS dementia complex, the most common neurologic syndrome, occurs as a late manifestation in 25–65% of AIDS patients and is characterized by poor memory, inability to concentrate, apathy, psychomotor retardation, and behavioral changes. Other neurologic diseases associated with HIV infection include toxoplasmosis, cryptococcosis, primary lymphoma of the central nervous system, and JC virus-induced progressive multifocal leukoencephalopathy. Mean survival time from onset of severe dementia is usually less than 6 months.
Pediatric AIDS patients also display neurologic abnormalities. These include seizure disorders, progressive loss of behavioral developmental milestones, encephalopathy, attention deficit disorders, and developmental delays. HIV encephalopathy may occur in as many as 12% of children, usually accompanied by profound immune deficiency. Bacterial pathogens predominate in pediatric AIDS as the most common cause of meningitis.
As children born with HIV infection are living to adolescence due to antiretroviral therapy, many appear to be at high risk for psychiatric disorders. The most common problems are anxiety disorders.
Opportunistic Infections
The predominant causes of morbidity and mortality among patients with late-stage HIV infection are opportunistic infections, ie, severe infections induced by agents that rarely cause serious disease in immune-competent individuals. Opportunistic infections usually do not occur in HIV-infected patients until CD4 T cell counts have dropped from the normal level of about 1000 cells/

L to less than 200 cells/

L. As treatments are developed for some common opportunistic pathogens and management of AIDS patients permits longer survivals, the spectrum of opportunistic infections changes.
The most common opportunistic infections in untreated AIDS patients include the following:
(1) Protozoa: Toxoplasma gondii, Isospora belli, Cryptosporidium species.
(2) Fungi: Candida albicans, Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum, Pneumocystis jiroveci.
(3) Bacteria: Mycobacterium avium-intracellulare, Mycobacterium tuberculosis, Listeria monocytogenes, Nocardia asteroides, Salmonella species, Streptococcus species.
(4) Viruses: Cytomegalovirus, herpes simplex virus, varicella-zoster virus, adenovirus, polyomavirus, JC virus, hepatitis B virus, hepatitis C virus.
Herpesvirus infections are common in AIDS patients, and multiple herpesviruses are frequently detected being shed in saliva. Cytomegalovirus retinitis is the most common severe ocular complication of AIDS.
Cancer
AIDS patients exhibit a marked predisposition to the development of cancer, another consequence of immune suppression. AIDS-associated cancers tend to be those with a viral cofactor and include non-Hodgkin's lymphoma (both systemic and central nervous system types), Kaposi's sarcoma, cervical cancer, and anogenital cancers. EB viral DNA is found in the majority of B cell malignancies classified as Burkitt's lymphoma and those of the central nervous system (but is not found in most of the systemic lymphomas). Polyomavirus SV40 has been detected in some non-Hodgkin's lymphomas. Burkitt's lymphoma occurs 1000 times more commonly in AIDS patients than in the general population.
Kaposi's sarcoma is a vascular tumor thought to be of endothelial origin that appears in skin, mucous membranes, lymph nodes, and visceral organs. Before this type of malignancy was observed in AIDS patients, it was considered to be a very rare cancer. Kaposi's sarcoma is 20,000 times more common in untreated AIDS patients than in the general population. Kaposi's sarcoma-associated herpesvirus, or HHV8, appears to be causally related to the cancer (see Chapter 33). Cervical cancer is caused by high-risk papillomaviruses; the anogenital cancers also may arise as a result of coinfections with human papillomaviruses (see Chapter 43).
Some non-AIDS-defining cancers are also more common in people with HIV. These include skin cancer, Hodgkin's disease, and prostate cancer.
Effective antiretroviral drug therapy has resulted in a marked reduction in the occurrence of Kaposi's sarcomas but has had less of an effect on the incidence of non-Hodgkin's lymphomas in HIV-infected individuals.
Immunity
HIV-infected persons develop both humoral and cell-mediated responses against HIV-related antigens. Antibodies to a number of viral antigens develop soon after infection (Table 44–3).

Table 44–3. Major Gene Products of HIV that Are Useful in Diagnosis of Infection.

[TD="bgcolor: #cccccc"][TABLE="width: 100%"]
[TR]

[/TD]
[/TR]
[TR]
[TD][TABLE="width: 100%"]
[TR="class: font12"]
[TH="bgcolor: #ffffff"]Gene Product[SUP]1[/SUP]
[/TH]
[TH="bgcolor: #ffffff"]Description[/TH]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]gp160[SUP]2[/SUP]
[/TD]
[TD="bgcolor: #ffffff"]Precursor of envelope glycoproteins[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]gp120[SUP]2[/SUP]
[/TD]
[TD="bgcolor: #ffffff"]Outer envelope glycoprotein of virion, SU[SUP]3[/SUP]
[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]p66[/TD]
[TD="bgcolor: #ffffff"]Reverse transcriptase and RNase H from polymerase gene product[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]p55[/TD]
[TD="bgcolor: #ffffff"]Precursor of core proteins, polyprotein from gag gene [/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]p51[/TD]
[TD="bgcolor: #ffffff"]Reverse transcriptase, RT[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]gp41[SUP]2[/SUP]
[/TD]
[TD="bgcolor: #ffffff"]Trans-membrane envelope glycoprotein, TM[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]p32[/TD]
[TD="bgcolor: #ffffff"]Integrase, IN[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]p24[SUP]2[/SUP]
[/TD]
[TD="bgcolor: #ffffff"]Nucleocapsid core protein of virion, CA[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]p17[/TD]
[TD="bgcolor: #ffffff"]Matrix core protein of virion, MA[/TD]
[/TR]
[/TABLE]
[/TD]
[/TR]
[TR]
[TD="bgcolor: #ffffff"]
[SUP]1[/SUP]Number refers to the approximate molecular mass of the protein in kilodaltons.
[SUP]2[/SUP]Antibodies to these viral proteins are the most commonly detected.
[SUP]3[/SUP]Two-letter abbreviation for viral protein.
[/TD]
[/TR]
[/TABLE]
Most infected individuals make neutralizing antibodies against HIV, directed against the envelope glycoprotein. However, the levels of neutralizing activity are low; many anti-envelope antibodies are nonneutralizing. It is believed that the dense glycosylation may inhibit binding of neutralizing antibody to the envelope protein. The envelope glycoprotein shows great sequence variability. This natural variation may allow the evolution of successive populations of resistant virus that escape recognition by existing neutralizing antibodies.
The neutralizing antibodies can be measured in vitro by inhibiting HIV infection of susceptible lymphocyte cell lines. Viral infection is quantified by (1) reverse transcriptase assay, which measures the enzyme activity of released HIV particles; (2) indirect immunofluorescence assay, which measures the percentage of infected cells; and (3) reverse transcriptase-polymerase chain reaction (RT-PCR) or branched-chain DNA (bDNA) amplification assays that measure HIV nucleic acids.
Cellular responses develop that are directed against HIV proteins. Cytotoxic T lymphocytes (CTLs) recognize env, pol, gag, and nef gene products; this reactivity is mediated by major histocompatibility complex-restricted CD3–CD8 lymphocytes. The env-specific reactivity occurs in nearly all infected people and decreases with progression of disease. Natural killer (NK) cell activity has also been detected against HIV-1 gp120.
It is not clear which host responses are important in providing protection against HIV infection or development of disease. A problem confronting AIDS vaccine research is that the correlates of protective immunity are not known, including the relative importance of humoral and cell-mediated immune responses.
Laboratory Diagnosis
Evidence of infection by HIV can be detected in three ways: (1) virus isolation, (2) serologic determination of antiviral antibodies, and (3) measurement of viral nucleic acid or antigens.
Virus Isolation
HIV can be cultured from lymphocytes in peripheral blood (and occasionally from specimens from other sites). The numbers of circulating infected cells vary with the stage of disease (Figure 44–5). Higher titers of virus are found in the plasma and in peripheral blood cells of patients with AIDS as compared with asymptomatic individuals. The magnitude of plasma viremia appears to be a better correlate of the clinical stage of HIV infection than the presence of any antibodies (Figure 44–7). The most sensitive virus isolation technique is to cocultivate the test sample with uninfected, mitogen-stimulated peripheral blood mononuclear cells. Primary isolates of HIV grow very slowly compared with laboratory-adapted strains. Viral growth is detected by testing culture supernatant fluids after about 7–14 days for viral reverse transcriptase activity or for virus-specific antigens (p24).

[TABLE="width: 100%"] [TR] [TD]Figure 44–7.

[/TD]
[/TR]
[TR]
[TD][TABLE="width: 100%"]
[TR]
[TD="align: center"]

[/TD]
[/TR]
[TR]
[TD="class: font11"]Pattern of HIV antibody responses related to the course of HIV infection. (PBL, peripheral blood lymphocytes; CTL, cytotoxic T lymphocytes.)
(Reproduced, with permission, from Weiss RA: How does HIV cause AIDS? Science 1993;260:1273.)
[/TD]
[/TR]
[/TABLE]
[/TD]
[/TR]
[/TABLE]
The vast majority of HIV-1 antibody-positive persons will have virus that can be cultured from their blood cells. However, virus isolation techniques are time-consuming and laborious and are limited to research studies. PCR amplification techniques are more commonly used for detection of virus in clinical specimens.
Serology
Test kits are commercially available for measuring antibodies by enzyme-linked immunoassay (EIA). If properly performed, these tests have a sensitivity and specificity exceeding 98%. When EIA-based antibody tests are used for screening populations with a low prevalence of HIV infections (eg, blood donors), a positive test in a serum sample must be confirmed by a repeat test. If the repeat EIA test is reactive, a confirmation test is performed to rule out false-positive EIA results. The most widely used confirmation assay is the Western blot technique, in which antibodies to HIV proteins of specific molecular weights can be detected. Antibodies to viral core protein p24 or envelope glycoproteins gp41, gp120, or gp160 are most commonly detected.
The response pattern against specific viral antigens changes over time as patients progress to AIDS. Antibodies to the envelope glycoproteins (gp41, gp120, gp160) are maintained, but those directed against the Gag proteins (p17, p24, p55) decline. The decline of anti-p24 may herald the beginning of clinical signs and other immunologic markers of progression (Figure 44–7).
Simple, rapid tests for detecting HIV antibodies are available for use in laboratories ill-equipped to perform EIA tests and in settings where test results are desired with little delay. The simple tests can be performed on blood or oral fluid and are based on principles such as particle agglutination or immunodot reactions. The most recent developments are rapid tests that can detect HIV antibodies in whole blood specimens that require no processing. These tests can be performed outside the traditional laboratory setting.
Home testing kits are available. The procedure involves placing drops of blood from a finger prick on a specially treated card. The card is then mailed to a licensed laboratory for testing.
The mean time to seroconversion after HIV infection is 3–4 weeks. Most individuals will have detectable antibodies within 6–12 weeks after infection, whereas virtually all will be positive within 6 months. HIV infection for longer than 6 months without a detectable antibody response is very uncommon.
Detection of Viral Nucleic Acid or Antigens
Amplification assays such as the RT-PCR, DNA PCR, and bDNA tests are commonly used to detect viral RNA in clinical specimens. The RT-PCR assay uses an enzymatic method to amplify HIV RNA; the bDNA assay amplifies viral RNA by sequential oligonucleotide hybridization steps. The tests can be quantitative when reference standards are used; appropriate positive and negative controls must be included with each test. These molecular-based tests are very sensitive and form the basis for plasma viral load determinations. HIV sequence heterogeneity may limit the sensitivity of these assays to detect HIV infections. The HIV RNA levels are important predictive markers of disease progression and valuable tools with which to monitor the effectiveness of antiviral therapies.
Early diagnosis of HIV infection in infants born to infected mothers can be accomplished using plasma HIV-1 RNA tests. The presence of maternal antibodies makes serologic tests uninformative.
Low levels of circulating HIV-1 p24 antigen can be detected in the plasma by EIA soon after infection. The antigen often becomes undetectable after antibodies develop (because the p24 protein is complexed with p24 antibodies) but may reappear late in the course of infection, indicating a poor prognosis.
Epidemiology
Worldwide Spread of AIDS
AIDS was first recognized in the United States in 1981 as a new disease entity in homosexual men. Twenty years later, AIDS had become a worldwide epidemic that continues to expand. The Joint United Nations Program on HIV/AIDS estimated that by the end of 2005, a total of 39 million people worldwide were living with HIV/AIDS, the majority having been infected by heterosexual contact (Figure 44–8). It was estimated that in that year, 2.8 million people died of AIDS and that 4 million new infections with HIV occurred, including 500,000 babies infected perinatally. By the year 2005, the World Health Organization estimated that more than 25 million people worldwide had died of AIDS and that over 15 million children had been orphaned, 12 million of whom were living in sub-Saharan Africa.

[TABLE="width: 100%"] [TR] [TD]Figure 44–8.

[/TD]
[/TR]
[TR]
[TD][TABLE="width: 100%"]
[TR]
[TD="align: center"]

[/TD]
[/TR]
[TR]
[TD="class: font11"]Adults and children estimated to be living with HIV/AIDS, by continent or region, as of December 2005. It is estimated that about 2.8 million people worldwide died of HIV/AIDS in 2005.
(Data from the Joint United Nations Program on HIV/AIDS.)
[/TD]
[/TR]
[/TABLE]
[/TD]
[/TR]
[/TABLE]
The epidemic varies by geographic region. Based on 2005 data, sub-Saharan Africa had the highest number of HIV infections (Figure 44–8). In certain high-prevalence cities in Africa, as many as one of every three adults was infected with the virus. Infections were spreading also in southern and southeastern Asia (especially in India, China, and Russia). Because AIDS tends to strike young adults and workers in their prime, the AIDS epidemic is having devastating effects on social and economic structures in some countries.
Group M viruses are responsible for most HIV-1 infections worldwide, but subtype distributions vary. Subtype C predominates in southern Africa, subtype A in West Africa, and subtype B in the United States, Europe, and Australia. HIV-2 has remained localized primarily to West Africa.
The World Health Organization estimates that of the 4 million new HIV infections each year, 90% are occurring in developing countries. In those countries, AIDS is overwhelmingly a heterosexually transmitted disease, and there are about equal numbers of male and female cases.
It is hypothesized that the rapid dissemination of HIV globally in the latter part of the 20th century was fostered by massive migration of rural inhabitants to urban centers, coupled with international movement of infected individuals as a consequence of civil disturbances, tourism, and business travels.
United States
The face of the AIDS epidemic has changed in the United States since 1981. At first, most of the cases occurred in homosexual men. Then the disease was identified in injecting drug users. By 2005, racial and ethnic minority communities were disproportionately affected, accounting for about two-thirds of reported HIV/AIDS cases. Heterosexual transmission was increasingly more common, and about one-quarter of new diagnoses were in women. Most heterosexually acquired AIDS cases were attributed to sexual contact with an injecting drug user or a partner with HIV infection.
By the end of 2005, over 1.5 million HIV/AIDS cases were estimated to have occurred (of which over 500,000 had resulted in death). Over 1 million persons are living with HIV/AIDS in the United States, and an estimated 40,000 new cases occur each year. The death rate decreased for the first time in 1996, reflecting the use of antiretroviral combination therapy and prevention of secondary opportunistic infections.
Pediatric AIDS increased as the number of HIV-infected women increased. It was estimated that 1650 newborns acquired the virus in 1991 in the United States. The numbers of new infections have been reduced dramatically by the development in 1994 of zidovudine antenatal, intrapartum, and neonatal therapy (see below). From transmission rates of 25–30% with no interventions, drug treatments have reduced transmission rates in the United States to less than 2%. There were only about 50 reported cases of pediatric AIDS in 2004. Mother-to-child transmission continues to occur because of undiagnosed HIV infection in the mother and lack of medical treatment.
The success in reducing perinatal HIV transmission in the United States has not been achieved in many poorer countries. Especially in sub-Saharan Africa, mother-to-child transmission rates remain high.
Routes of Transmission
High titers of HIV are found in two body fluids-blood and semen. HIV is transmitted during sexual contact (including genital-oral sex), through parenteral exposure to contaminated blood or blood products, and from mother to child during the perinatal period. The presence of other sexually transmitted diseases such as syphilis, gonorrhea, or herpes simplex type 2 increases the risk of sexual HIV transmission as much as a hundredfold because the inflammation and sores facilitate the transfer of HIV across mucosal barriers. Asymptomatic virus-positive individuals can transmit the virus. Since the first description of AIDS, promiscuous homosexual activity has been recognized as a major risk factor for acquisition of the disease. The risk increases in proportion to the number of sexual encounters with different partners.
Transfusion of infectious blood or blood products is an effective route for viral transmission. For example, over 90% of hemophiliac recipients of contaminated clotting factor concentrates in the United States (before HIV was detected) developed antibodies to HIV. Injection users of illicit drugs are commonly infected through the use of contaminated needles. Injection drug use accounts for a substantial proportion of new AIDS cases.
Careful testing is necessary to ensure a safe blood supply. The World Health Organization has reported that voluntary unremunerated blood donation is far safer than paid donations. It was reported in 1996 that the risk of transfusion-transmitted HIV infection in the United States was very small (about 1:500,000).
Mother-to-infant transmission rates vary from 13% to 40% in untreated women. Infants can become infected in utero, during the birth process, or, more commonly, through breastfeeding. In the absence of breastfeeding, about 30% of infections occur in utero and 70% during delivery. Data indicate that from one-third to one-half of perinatal HIV infections in Africa are due to breastfeeding. Transmission during breastfeeding usually occurs early (by 6 months). High maternal viral loads are a risk factor for transmission.
Health care workers have been infected by HIV following a needlestick with contaminated blood. The numbers of infections are relatively few in comparison with the number of needlesticks that have occurred involving contaminated blood (estimated risk of transmission is about 0.3%). The risk of transmission is even lower after a mucous membrane exposure to infected blood (about 0.09%).
The routes of transmission (blood, sex, and birth) described above account for almost all HIV infections. There has been considerable concern that in rare circumstances other types of transmission may occur, such as through "casual" contact with HIV-infected persons or insect vectors, but there is no evidence of virus transmission under these casual conditions.
Prevention, Treatment, & Control
Antiviral Drugs
A growing number of antiviral drugs are approved for treatment of HIV infections (see Chapter 30). Classes of drugs include both nucleoside and nonnucleoside inhibitors of the viral enzyme reverse transcriptase and inhibitors of the viral protease enzyme. The protease inhibitors are potent antiviral drugs because the protease activity is absolutely essential for production of infectious virus, and the viral enzyme is distinct from human cell proteases. The newest class of drugs-fusion inhibitors first approved in 2003-blocks virus entry into cells.
Therapy with combinations of antiretroviral drugs, referred to as highly active antiretroviral therapy (HAART), became available in 1996. It oftentimes can suppress viral replication to below limits of detection in plasma, decrease viral loads in lymphoid tissues, allow the recovery of immune responses to opportunistic pathogens, and prolong patient survival. However, HAART has failed to cure HIV-1 infections. The virus persists in reservoirs of long-lived, latently infected cells, including memory CD4 T cells. When HAART is discontinued or there is treatment failure, virus production rebounds.
Whereas monotherapy usually results in the rapid emergence of drug-resistant mutants of HIV, combination therapy, which targets multiple steps in virus replication, usually delays selection of HIV mutants. However, mutants that arise which are resistant to one protease inhibitor are often resistant to other protease inhibitors as well.
Transmission of drug-resistant variants may affect future therapy options. In 2004 and 2005, treatment-naïve patients with newly diagnosed HIV infections were found to carry virus with drug-resistant mutations in 8% and 10% of cases in the United States and Europe, respectively. Among perinatally infected infants in the United States in 2002, 19% had virus with drug-resistant mutations.
Results with combination therapy have been successful and have turned HIV infection into a chronic, treatable disease. Prolonged suppression of viral replication can be achieved, along with restoration of immune function. However, additional drug development is needed. Current drug regimens are often complicated and expensive, cannot be tolerated by all patients, have toxic side effects (including lipodystrophy), and lead to a number of treatment failures. The first once-daily pill that combines three HIV drugs was approved in the United States in 2006. The majority of infected persons worldwide do not have access to any HIV drugs.
Zidovudine (azidothymidine; AZT) can significantly reduce the transmission of HIV from mother to infant. A regimen of AZT therapy of the mother during pregnancy and during the birth process and of the baby after birth reduced the risk of perinatal transmission by 65–75% (from about 25% to less than 2%). This treatment decreases vertical transmission at all levels of maternal viral load. A shorter course of AZT given to infected mothers or a simple nevirapine regimen has been shown to reduce transmission by 50% and to be safe for use in developing nations. However, the high rate of HIV transmission by breastfeeding can undermine the benefits of maternal perinatal drug treatment.
Vaccines Against HIV
A safe and effective vaccine offers the best hope of controlling the worldwide AIDS epidemic. As of 2006, many candidate vaccines are under development and are in different stages of testing. Viral vaccines are typically preventive, ie, given to uninfected individuals to prevent either infection or disease. Consideration is also being given to the possibility of therapeutic HIV vaccines, whereby HIV-infected individuals would be treated to boost anti-HIV immune responses, decrease the numbers of virus-infected cells, or delay the onset of AIDS. Vaccine development is difficult because HIV mutates rapidly, is not expressed in all cells that are infected, and is not completely cleared by the host immune response after primary infection. HIV isolates show a marked variation, especially in the envelope antigens-variability that probably promotes the emergence of neutralization-resistant mutants. As the correlates of protective immunity are not known, it is unclear what immune responses a vaccine should elicit.
Because of the safety concerns, vaccines based on attenuated or inactivated HIV or on simian isolates are viewed with apprehension. Recombinant viral proteins-especially those of the envelope glycoproteins-are likely candidates, whether delivered with adjuvants or with heterologous viral vectors. Many novel vaccination methods are also under investigation. Gene therapy approaches are being developed that are designed to achieve "intracellular immunization," ie, to genetically alter target cells in such a way as to make them resistant to HIV.
A large hurdle for vaccine development is the lack of an appropriate animal model for HIV. Chimpanzees are the only animals that are susceptible to HIV. Not only is the supply scarce, but chimpanzees develop only viremia and antibodies; they do not develop immunodeficiency. The SIV-macaque model of simian AIDS does develop disease and is useful for vaccine development studies.
Control Measures
Without control by drugs or vaccines, the only way to avoid epidemic spread of HIV is to maintain a lifestyle that minimizes or eliminates the high-risk factors discussed above. No cases have been documented to result from such common exposures as sneezing, coughing, sharing meals, or other casual contacts.
Because HIV may be transmitted in blood, all donor blood should be tested for antibody. Properly conducted antibody tests appear to detect almost all HIV-1 and HIV-2 carriers. In settings with widespread screening of blood donors for viral exposure and the rejection of contaminated blood, transmission by blood transfusion has virtually disappeared.
Public health authorities have recommended that persons reported to have an HIV infection be given the following information and advice:
(1) Almost all persons will remain infected for life and will develop the disease.
(2) Although asymptomatic, such individuals may transmit HIV to others. Regular medical evaluation and follow-up are advised.
(3) Infected persons should refrain from donating blood, plasma, body organs, other tissues, or sperm.
(4) There is a risk of infecting others by sexual intercourse (vaginal or anal), by oral-genital contact, or by sharing of needles. The consistent and proper use of condoms can reduce transmission of the virus, though protection is not absolute.
(5) Toothbrushes, razors, and other implements that could become contaminated with blood should not be shared.
(6) Seropositive women or women with seropositive sexual partners are themselves at increased risk of acquiring AIDS. If they become pregnant, their offspring also are at high risk of acquiring AIDS.
(7) After accidents that result in bleeding, contaminated surfaces should be cleaned with household bleach freshly diluted 1:10 in water.
(8) Devices that have punctured the skin-eg, hypodermic and acupuncture needles-should be steam-sterilized by autoclaving before reuse or should be safely discarded. Dental instruments should be heat-sterilized between patients. Whenever possible, disposable needles and equipment should be used.
(9) When seeking medical or dental care for intercurrent illness, infected persons should inform those responsible for their care that they are seropositive, so that appropriate evaluation can be undertaken and precautions taken to prevent transmission to others.
(10) Testing for HIV antibody should be offered to persons who may have been infected as a result of their contact with seropositive individuals (eg, sexual partners, persons with whom needles have been shared, infants born to seropositive mothers).
(11) Most persons with a positive test for HIV do not need to consider a change in employment unless their work involves significant potential for exposing others to their blood or other body fluids. There is no evidence of HIV transmission by food handling.
(12) Seropositive persons in the health care professions who perform invasive procedures or have skin lesions should take precautions similar to those recommended for hepatitis B carriers to protect patients from the risk of infection.
(13) Children with positive tests should be allowed to attend school, since casual person-to-person contact of schoolchildren poses no risk. However, a more restricted environment is advisable for preschool children or children who lack control of their body secretions, display biting behavior, or have oozing lesions.
Health Education
Without a vaccine or treatment, the prevention of cases of AIDS relies on the success of education projects involving behavioral changes. The health education messages for the general public have been summarized as follows: (1) Any sexual intercourse (outside of mutually monogamous HIV antibody-negative relationships) should be protected by a condom. (2) Do not share unsterile needles or syringes. (3) All women who have been potentially exposed should seek HIV antibody testing before becoming pregnant and, if the test is positive, should consider avoiding pregnancy. (4) HIV-infected mothers should avoid breast feeding to reduce transmission of the virus to their children if safe alternative feeding options are available.
[/TD]
[/TR]
[/TABLE]

[TD="bgcolor: #ffffff"]References
[TABLE="width: 100%"]
[TR]
[TD="class: contentBody"]Apetrei C, Robertson DL, Marx PA: The history of SIVs and AIDS: Epidemiology, phylogeny, and biology of isolates from naturally SIV infected non-human primates (NHP) in Africa. Front in Biosci 2004;9:225. [PMID: 14766362]

[/TD]

[TD="class: contentBody"]Desrosiers RC: Nonhuman lentiviruses. In: Fields Virology, 4th ed. Knipe DM et al (editors). Lippincott Williams & Wilkins, 2001.

[/TD]

[TD="class: contentBody"]Dybul M et al (editors): Guidelines for using antiretroviral agents among HIV-infected adults and adolescents: The Panel on Clinical Practices for HIV. Ann Intern Med 2002;137:381. [PMID: 12617573]

[/TD]

[TD="class: contentBody"]Freed EO, Martin MA: HIVs and their replication. In: Fields Virology, 4th ed. Knipe DM et al (editors). Lippincott Williams & Wilkins, 2001.

[/TD]

[TD="class: contentBody"]Hahn BH et al: AIDS as a zoonosis: Scientific and public health implications. Science 2000;287:607. [PMID: 10649986]

[/TD]

[TD="class: contentBody"]Moore JP, Doms RW: The entry of entry inhibitors: A fusion of science and medicine. Proc Natl Acad Sci U S A 2003;100: 10598. [PMID: 12960367]

[/TD]

[TD="class: contentBody"]Patrick MK, Johnston JB, Power C: Lentiviral neuropathogenesis: Comparative neuroinvasion, neurotropism, neurovirulence, and host neurosusceptibility. J Virol 2002;76:7923. [PMID: 12133996]

[/TD]

[TD="class: contentBody"]Paul ME, Schearer WT: Pediatric human immunodeficiency virus infection. In: Pediatric Allergy: Principles and Practice . Leung DYM, Sampson HA, Geha RS, Szefler SJ (editors). Mosby, 2003.

[/TD]

[TD="class: contentBody"]Schreiber GB et al: The risk of transfusion-transmitted viral infections. N Engl J Med 1996;334:1685. [PMID: 8637512]

[/TD]

[TD="class: contentBody"]Sepkowitz KA: AIDS-the first 20 years. N Engl J Med 2001;344: 1764.

[/TD]

[TD="class: contentBody"]Twenty-five years of HIV/AIDS-United States, 1981–2006. MMWR Morb Mortal Wkly Rep 2006;55 (No. 21).

[/TD]

[TD="class: contentBody"]U.S. Public Health Service guidelines for testing and counseling blood and plasma donors for human immunodeficiency virus type 1 antigen. MMWR Morb Mortal Wkly Rep 1996;45 (RR-2).

[/TD]

[TD="class: contentBody"]Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Morb Mortal Wkly Rep 2005;54(RR-9[/TD]

[/TD]
[/TR]
[/TABLE]

 

[pakamwam]

[TABLE="width: 100%"] [TR] [TD="align: center"]

[TD="bgcolor: #ffffff"]HIV in humans originated from cross-species infections by simian viruses in rural Africa, probably due to direct human contact with infected primate blood. Current evidence is that the primate counterparts of HIV-1 and HIV-2 were transmitted to humans on multiple (at least seven) different occasions. Sequence evolution analyses place the introduction of SIV[SUB]cpz[/SUB] into humans that gave rise to HIV-1 group M at about 1930. Presumably, such transmissions occurred repeatedly over the ages, but particular social, economic, and behavioral changes that occurred in the mid 20th century provided circumstances that allowed these virus infections to expand, become well-established in humans, and reach epidemic proportions.
Disinfection & Inactivation
HIV is completely inactivated (

10[SUP]5[/SUP] units of infectivity) by treatment for 10 minutes at room temperature with any of the following: 10% household bleach, 50% ethanol, 35% isopropanol, 1% Nonidet P40, 0.5% Lysol, 0.5% paraformaldehyde, or 0.3% hydrogen peroxide. The virus is also inactivated by extremes of pH (pH 1.0, pH 13.0). However, when HIV is present in clotted or unclotted blood in a needle or syringe, exposure to undiluted bleach for at least 30 seconds is necessary for inactivation.
The virus is not inactivated by 2.5% Tween 20. Although paraformaldehyde inactivates virus free in solution, it is not known if it penetrates tissues sufficiently to inactivate all virus that might be present in cultured cells or tissue specimens.
HIV is readily inactivated in liquids or 10% serum by heating at 56 °C for 10 minutes, but dried proteinaceous material affords marked protection. Lyophilized blood products would need to be heated at 68 °C for 72 hours to ensure inactivation of contaminating virus.
Animal Lentivirus Systems
Insights into the biologic characteristics of lentivirus infections have been gained from experimental infections, including sheep with visna virus (Table 44–2). Natural disease patterns vary among species, but certain common features are recognized.
(1) Viruses are transmitted by exchange of body fluids.
(2) Virus persists indefinitely in infected hosts, though it may be present at very low levels.
(3) Viruses have high mutation rates, and different mutants will be selected under different conditions (host factors, immune responses, tissue types). Infected hosts contain "swarms" of closely related viral genomes, known as quasi species.
(4) Virus infection progresses slowly through specific stages. Cells in the macrophage lineage play central roles in the infection. Lentiviruses differ from other retroviruses in that they can infect nondividing, terminally differentiated cells. However, those cells must be activated before viral replication ensues and progeny virus is produced. Virus is cell-associated in monocytes and macrophages, but only about one cell per million is infected. Monocytes carry the virus around the body in a form that the immune system cannot recognize, seeding other tissues. Lymphocyte-tropic strains of virus tend to cause highly productive infections, whereas replication of macrophage-tropic virus is restricted.
(5) It may take years for disease to develop. Infected hosts usually make antibodies, but they do not clear the infection, so virus persists lifelong. New antigenic variants periodically arise in infected hosts, with most mutations occurring in envelope glycoproteins. Clinical symptoms may develop at any time from 3 months to many years after infection. The exceptions to long incubation periods for lentivirus disease include AIDS in children, infectious anemia in horses, and encephalitis in young goats.
Host factors important in pathogenesis of disease include age (the young are at greater risk), stress (may trigger disease), genetics (certain breeds of animals are more susceptible), and concurrent infections (may exacerbate disease or facilitate virus transmission).
The diseases in ungulates (horses, cattle, sheep, and goats) are not complicated by opportunistic secondary infections. Equine infectious anemia virus can be spread among horses by blood-sucking horseflies, the only lentivirus known to be transmitted by an insect vector.
Simian lentiviruses share molecular and biologic characteristics with HIV and cause an AIDS-like disease in rhesus macaques. The SIV model is important for understanding disease pathogenesis and developing vaccine and treatment strategies.
Virus Receptors
All primate lentiviruses use as a receptor the CD4 molecule, which is expressed on macrophages and T lymphocytes. A second coreceptor in addition to CD4 is necessary for HIV-1 to gain entry to cells. The second receptor is required for fusion of the virus with the cell membrane (Figure 44–4). The virus first binds to CD4 and then to the coreceptor. These interactions cause conformational changes in the viral envelope, activating the gp41 fusion peptide and triggering membrane fusion. Chemokine receptors serve as HIV-1 second receptors. (Chemokines are soluble factors with chemoattractant and cytokine properties.) CCR5, the receptor for chemokines RANTES, MIP-1

, and MIP-1

, is the predominant coreceptor for macrophage-tropic strains of HIV-1, whereas CXCR4, the receptor for chemokine SDF-1, is the coreceptor for lymphocyte-tropic strains of HIV-1. The chemokine receptors used by HIV for cell entry are found on lymphocytes, macrophages, and thymocytes as well as on neurons and cells in the colon and cervix. Individuals who possess homozygous deletions in CCR5 and produce mutant forms of the protein may be protected from infection by HIV-1; mutations in the CCR5 gene promoter appear to delay disease progression. The requirement for a coreceptor for HIV fusion with cells provided new targets for antiviral therapeutic strategies, with the first HIV entry inhibitor licensed in the United States in 2003.

[TABLE="width: 100%"] [TR] [TD]Figure 44–4.

[/TD]

[TD="class: font11"]HIV fusion with target cell. Gp120 binds to the CD4 molecule and then to the coreceptor (CCR5 or CXCR4). This causes a conformational change in the viral envelope proteins, affecting gp41 so that the fusion peptide penetrates the cell and leads to membrane fusion.
(Reproduced, with permission, from Binley J, Moore JP: The viral mousetrap. Nature 1997;387:346.)
[/TD]

[/TD]
[/TR]
[/TABLE]
A dendritic cell-specific lectin, DC-SIGN, appears to bind HIV-1 but not to mediate cell entry. Rather, it may facilitate transport of HIV by dendritic cells to lymphoid organs and enhance infection of T cells.
[/TD]
[/TR]
[/TABLE]

[TABLE="width: 100%"] [TR] [TD="align: center"]

[TD="bgcolor: #ffffff"]HIV Infections in Humans
Pathogenesis & Pathology
Overview of Course of HIV Infection
The typical course of untreated HIV infection spans about a decade (Figure 44–5). Stages include the primary infection, dissemination of virus to lymphoid organs, clinical latency, elevated HIV expression, clinical disease, and death. The duration between primary infection and progression to clinical disease averages about 10 years. In untreated cases, death usually occurs within 2 years after the onset of clinical symptoms.

[TABLE="width: 100%"] [TR] [TD]Figure 44–5.

[/TD]

[TD="class: font11"]Typical course of untreated HIV infection. During the early period after primary infection, there is widespread dissemination of virus and a sharp decrease in the number of CD4 T cells in peripheral blood. An immune response to HIV ensues, with a decrease in detectable viremia followed by a prolonged period of clinical latency. Sensitive assays for viral RNA show that virus is present in the plasma at all times. The CD4 T cell count continues to decrease during the following years until it reaches a critical level below which there is a substantial risk of opportunistic diseases.
(Reproduced, with permission, from Pantaleo G, Graziosi C, Fauci AS: New concepts in the immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 1993;328:327.)
[/TD]

[/TD]
[/TR]
[/TABLE]
Following primary infection, there is a 4- to 11-day period between mucosal infection and initial viremia; the viremia is detectable for about 8–12 weeks. Virus is widely disseminated throughout the body during this time, and the lymphoid organs become seeded. An acute mononucleosis-like syndrome develops in many patients (50–75%) 3–6 weeks after primary infection. There is a significant drop in numbers of circulating CD4 T cells at this early time. An immune response to HIV occurs 1 week to 3 months after infection, plasma viremia drops, and levels of CD4 cells rebound. However, the immune response is unable to clear the infection completely, and HIV-infected cells persist in the lymph nodes.
This period of clinical latency may last for as long as 10 years. During this time, there is a high level of ongoing viral replication. It is estimated that 10 billion HIV particles are produced and destroyed each day. The half-life of the virus in plasma is about 6 hours, and the virus life cycle (from the time of infection of a cell to the production of new progeny that infect the next cell) averages 2.6 days. CD4 T lymphocytes, major targets responsible for virus production, appear to have similar high turnover rates. Once productively infected, the half-life of a CD4 lymphocyte is about 1.6 days. Because of this rapid viral proliferation and the inherent error rate of the HIV reverse transcriptase, it is estimated that every nucleotide of the HIV genome probably mutates on a daily basis.
Eventually, the patient will develop constitutional symptoms and clinically apparent disease, such as opportunistic infections or neoplasms. Higher levels of virus are readily detectable in the plasma during the advanced stages of infection. HIV found in patients with late-stage disease is usually much more virulent and cytopathic than the strains of virus found early in infection. Often, a shift from monocyte-tropic or macrophage-tropic (M-tropic) strains of HIV-1 to lymphocyte-tropic (T-tropic) variants accompanies progression to AIDS.
CD4 T Lymphocytes and Memory Cells
The cardinal feature of HIV infection is the depletion of T helper-inducer lymphocytes—the result of HIV replication in this population of lymphocytes as well as of the death of uninfected T cells by indirect mechanisms. The T cells express the CD4 phenotypic marker on their surface. The CD4 molecule is the major receptor for HIV; it has a high affinity for the viral envelope. The HIV coreceptor on lymphocytes is the CXCR4 chemokine receptor.
Early in infection, primary HIV isolates are M-tropic. However, all strains of HIV infect primary CD4 T lymphocytes (but not immortalized T cell lines in vitro). As the infection progresses, the dominant M-tropic viruses are replaced by T-tropic viruses. Laboratory adaptation of these primary isolates in immortalized T cell lines results in loss of ability to infect monocytes and macrophages.
The consequences of CD4 T cell dysfunction caused by HIV infection are devastating because the CD4 T lymphocyte plays a critical role in the human immune response. It is responsible directly or indirectly for induction of a wide array of lymphoid and nonlymphoid cell functions. These effects include activation of macrophages; induction of functions of cytotoxic T cells, natural killer cells, and B cells; and secretion of a variety of soluble factors that induce growth and differentiation of lymphoid cells and affect hematopoietic cells.
At any given time, only a small fraction of CD4 T cells are productively infected. Many infected T cells are killed, but a fraction survive and revert to a resting memory state. There is little or no virus gene expression in the memory cells, and they provide a long-term, stable latent reservoir for the virus. When exposed to antigen, the memory cells become activated and release infectious virus. The latent reservoir of infected memory cells decays very slowly, with a half-life of at least 43 months. It is unlikely that an HIV infection can be cured; if there were a million infected memory cells in the body, it would take about 70 years for them to decay.
Monocytes and Macrophages
Monocytes and macrophages play a major role in the dissemination and pathogenesis of HIV infection. Certain subsets of monocytes express the CD4 surface antigen and therefore bind to the envelope of HIV. The HIV coreceptor on monocytes and macrophages is the CCR5 chemokine receptor. In the brain, the major cell types infected with HIV appear to be the monocytes and macrophages, and this may have important consequences for the development of neuropsychiatric manifestations associated with HIV infection. Infected pulmonary alveolar macrophages may play a role in the interstitial pneumonitis seen in certain patients with AIDS.
Macrophage-tropic strains of HIV predominate early after infection, and these strains are responsible for initial infections even when the transmitting source contains both M-tropic and T-tropic viruses.
It is believed that monocytes and macrophages serve as major reservoirs for HIV in the body. Unlike the CD4 T lymphocyte, the monocyte is relatively refractory to the cytopathic effects of HIV, so that the virus not only can survive in this cell but can be transported to various organs in the body (such as the lungs and brain). Infected macrophages may continue to produce virus for a long period of time.
Lymphoid Organs
Lymphoid organs play a central role in HIV infection. Lymphocytes in the peripheral blood represent only about 2% of the total lymphocyte pool, the remainder being located chiefly in lymphoid organs. It is in the lymphoid organs that specific immune responses are generated. The network of follicular dendritic cells in the germinal centers of lymph nodes traps antigens and stimulates an immune response. Throughout the course of untreated infection—even during the stage of clinical latency—HIV is actively replicating in lymphoid tissues. The microenvironment of the lymph node is ideal for the establishment and spread of HIV infection. Cytokines are released, activating a large pool of CD4 T cells that are highly susceptible to HIV infection. As the late stages of HIV disease progress, the architecture of the lymph nodes becomes disrupted.
Neural Cells
Neurologic abnormalities are common in late stages of infection and are an AIDS-defining condition. Central nervous system disease occurs to varying degrees in 40–90% of patients. These include HIV encephalopathy, peripheral neuropathies, and—most serious—AIDS dementia complex. Both direct and indirect pathogenic mechanisms might explain the neuropsychiatric manifestations of HIV infection. The predominant cell types in the brain that are infected with HIV are monocytes and macrophages. Virus may enter the brain through infected monocytes and release cytokines that are toxic to neurons as well as chemotactic factors that lead to infiltration of the brain with inflammatory cells. HIV is present rarely, if at all, in neurons, oligodendrocytes, and astrocytes.
Viral Coinfections
Activation signals are required for the establishment of a productive HIV infection. In the HIV-infected individual, a wide range of in vivo antigenic stimuli seem to serve as cellular activators. For example, active infection by Mycobacterium tuberculosis substantially increases plasma viremia. Other concomitant viral infections—with EB virus, cytomegalovirus, herpes simplex virus, or hepatitis B virus—may serve as cofactors of AIDS. Hepatitis C virus coinfection, which occurs in 15–30% of HIV cases in the United States and often results in liver disease, is a leading cause of morbidity and mortality in HIV-infected persons. There is also a high prevalence of cytomegalovirus infection in HIV-positive individuals.
Coinfections with two different strains of HIV can occur. There are documented cases of superinfection with a second strain in an HIV-infected individual, even in the presence of a strong CD8 T cell response to the first strain. HIV superinfection is considered to be a rare event.
Clinical Findings
Symptoms of acute HIV infection are nonspecific and include fatigue, rash, headache, nausea, and night sweats. AIDS is characterized by pronounced suppression of the immune system and development of a wide variety of severe opportunistic infections or unusual neoplasms (especially Kaposi's sarcoma). The more serious symptoms in adults are often preceded by a prodrome ("diarrhea and dwindling") that can include fatigue, malaise, weight loss, fever, shortness of breath, chronic diarrhea, white patches on the tongue (hairy leukoplakia, oral candidiasis), and lymphadenopathy. Disease symptoms in the gastrointestinal tract from the esophagus to the colon are a major cause of debility. With no treatment, the interval between primary infection with HIV and the first appearance of clinical disease is usually long in adults, averaging about 8–10 years. Death occurs about 2 years later.
Plasma Viral Load
The amount of HIV in the blood (viral load) is of significant prognostic value. There are continual rounds of viral replication and cell killing in each patient, and the steady-state level of virus in the blood varies from individual to individual. This level reflects the total number of productively infected cells and their average burst size. It turns out that a single measurement of plasma viral load about 6 months after infection is able to predict the subsequent risk of development of AIDS in men several years later (Figure 44–6). However, more recent data suggest a gender difference in this parameter—in women, the viral load may be less predictive of progression to AIDS. Plasma HIV RNA levels can be determined using a variety of commercially available assays. The plasma viral load appears to be the best predictor of long-term clinical outcome, whereas CD4 lymphocyte counts are the best predictor of short-term risk of developing an opportunistic disease. Plasma viral load measurements are a critical element in assessing the effectiveness of antiretroviral drug therapy.

[TABLE="width: 100%"] [TR] [TD]Figure 44–6.

[/TD]
[/TR]
[TR]
[TD][TABLE="width: 100%"]
[TR]
[TD="align: center"]

[/TD]
[/TR]
[TR]
[TD="class: font11"]Prognostic value of HIV-1 RNA levels in the plasma (viral load). The virologic setpoint predicts the long-term clinical outcome.
(Reproduced, with permission, from Ho DD: Viral counts count in HIV infection. Science 1996;272:1124.)
[/TD]
[/TR]
[/TABLE]
[/TD]
[/TR]
[/TABLE]
Pediatric AIDS
The responses of infected neonates are different from those observed in HIV-infected adults. Pediatric AIDS—acquired from infected mothers—usually presents with clinical symptoms by 2 years of age; death follows in another 2 years. The neonate is particularly susceptible to the devastating effects of HIV because the immune system has not developed at the time of primary infection. Clinical findings may include lymphoid interstitial pneumonitis, pneumonia, severe oral candidiasis, encephalopathy, wasting, generalized lymphadenopathy, bacterial sepsis, hepatosplenomegaly, diarrhea, and growth retardation.
Children with perinatally acquired HIV-1 infection—if untreated—have a very poor prognosis. A high rate of disease progression occurs in the first few years of life. High levels of plasma HIV-1 load appear to predict infants at risk of rapid progression of disease. The pattern of viral replication in infants differs from that in adults. Viral RNA load levels are generally low at birth, suggesting infection acquired close to that time; RNA levels then rise rapidly within the first 2 months of life and are followed by a slow decline until the age of 24 months, suggesting that the immature immune system has difficulty containing the infection. A small percentage of infants (

5%) display transient HIV infections, suggesting that some infants can clear the virus.
Neurologic Disease
Neurologic dysfunction occurs frequently in HIV-infected persons. Forty to 90 percent of patients have neurologic symptoms, and many are found during autopsy to have neuropathologic abnormalities.
Several distinct neurologic syndromes that occur frequently include subacute encephalitis, vacuolar myelopathy, aseptic meningitis, and peripheral neuropathy. AIDS dementia complex, the most common neurologic syndrome, occurs as a late manifestation in 25–65% of AIDS patients and is characterized by poor memory, inability to concentrate, apathy, psychomotor retardation, and behavioral changes. Other neurologic diseases associated with HIV infection include toxoplasmosis, cryptococcosis, primary lymphoma of the central nervous system, and JC virus-induced progressive multifocal leukoencephalopathy. Mean survival time from onset of severe dementia is usually less than 6 months.
Pediatric AIDS patients also display neurologic abnormalities. These include seizure disorders, progressive loss of behavioral developmental milestones, encephalopathy, attention deficit disorders, and developmental delays. HIV encephalopathy may occur in as many as 12% of children, usually accompanied by profound immune deficiency. Bacterial pathogens predominate in pediatric AIDS as the most common cause of meningitis.
As children born with HIV infection are living to adolescence due to antiretroviral therapy, many appear to be at high risk for psychiatric disorders. The most common problems are anxiety disorders.
Opportunistic Infections
The predominant causes of morbidity and mortality among patients with late-stage HIV infection are opportunistic infections, ie, severe infections induced by agents that rarely cause serious disease in immune-competent individuals. Opportunistic infections usually do not occur in HIV-infected patients until CD4 T cell counts have dropped from the normal level of about 1000 cells/

L to less than 200 cells/

L. As treatments are developed for some common opportunistic pathogens and management of AIDS patients permits longer survivals, the spectrum of opportunistic infections changes.
The most common opportunistic infections in untreated AIDS patients include the following:
(1) Protozoa: Toxoplasma gondii, Isospora belli, Cryptosporidium species.
(2) Fungi: Candida albicans, Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum, Pneumocystis jiroveci.
(3) Bacteria: Mycobacterium avium-intracellulare, Mycobacterium tuberculosis, Listeria monocytogenes, Nocardia asteroides, Salmonella species, Streptococcus species.
(4) Viruses: Cytomegalovirus, herpes simplex virus, varicella-zoster virus, adenovirus, polyomavirus, JC virus, hepatitis B virus, hepatitis C virus.
Herpesvirus infections are common in AIDS patients, and multiple herpesviruses are frequently detected being shed in saliva. Cytomegalovirus retinitis is the most common severe ocular complication of AIDS.
Cancer
AIDS patients exhibit a marked predisposition to the development of cancer, another consequence of immune suppression. AIDS-associated cancers tend to be those with a viral cofactor and include non-Hodgkin's lymphoma (both systemic and central nervous system types), Kaposi's sarcoma, cervical cancer, and anogenital cancers. EB viral DNA is found in the majority of B cell malignancies classified as Burkitt's lymphoma and those of the central nervous system (but is not found in most of the systemic lymphomas). Polyomavirus SV40 has been detected in some non-Hodgkin's lymphomas. Burkitt's lymphoma occurs 1000 times more commonly in AIDS patients than in the general population.
Kaposi's sarcoma is a vascular tumor thought to be of endothelial origin that appears in skin, mucous membranes, lymph nodes, and visceral organs. Before this type of malignancy was observed in AIDS patients, it was considered to be a very rare cancer. Kaposi's sarcoma is 20,000 times more common in untreated AIDS patients than in the general population. Kaposi's sarcoma-associated herpesvirus, or HHV8, appears to be causally related to the cancer (see Chapter 33). Cervical cancer is caused by high-risk papillomaviruses; the anogenital cancers also may arise as a result of coinfections with human papillomaviruses (see Chapter 43).
Some non-AIDS-defining cancers are also more common in people with HIV. These include skin cancer, Hodgkin's disease, and prostate cancer.
Effective antiretroviral drug therapy has resulted in a marked reduction in the occurrence of Kaposi's sarcomas but has had less of an effect on the incidence of non-Hodgkin's lymphomas in HIV-infected individuals.
Immunity
HIV-infected persons develop both humoral and cell-mediated responses against HIV-related antigens. Antibodies to a number of viral antigens develop soon after infection (Table 44–3).

Table 44–3. Major Gene Products of HIV that Are Useful in Diagnosis of Infection.

[TD="bgcolor: #cccccc"][TABLE="width: 100%"]
[TR]

[/TD]
[/TR]
[TR]
[TD][TABLE="width: 100%"]
[TR="class: font12"]
[TH="bgcolor: #ffffff"]Gene Product[SUP]1[/SUP]
[/TH]
[TH="bgcolor: #ffffff"]Description[/TH]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]gp160[SUP]2[/SUP]
[/TD]
[TD="bgcolor: #ffffff"]Precursor of envelope glycoproteins[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]gp120[SUP]2[/SUP]
[/TD]
[TD="bgcolor: #ffffff"]Outer envelope glycoprotein of virion, SU[SUP]3[/SUP]
[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]p66[/TD]
[TD="bgcolor: #ffffff"]Reverse transcriptase and RNase H from polymerase gene product[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]p55[/TD]
[TD="bgcolor: #ffffff"]Precursor of core proteins, polyprotein from gag gene [/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]p51[/TD]
[TD="bgcolor: #ffffff"]Reverse transcriptase, RT[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]gp41[SUP]2[/SUP]
[/TD]
[TD="bgcolor: #ffffff"]Trans-membrane envelope glycoprotein, TM[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]p32[/TD]
[TD="bgcolor: #ffffff"]Integrase, IN[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]p24[SUP]2[/SUP]
[/TD]
[TD="bgcolor: #ffffff"]Nucleocapsid core protein of virion, CA[/TD]
[/TR]
[TR="class: font12"]
[TD="bgcolor: #ffffff"]p17[/TD]
[TD="bgcolor: #ffffff"]Matrix core protein of virion, MA[/TD]
[/TR]
[/TABLE]
[/TD]
[/TR]
[TR]
[TD="bgcolor: #ffffff"]
[SUP]1[/SUP]Number refers to the approximate molecular mass of the protein in kilodaltons.
[SUP]2[/SUP]Antibodies to these viral proteins are the most commonly detected.
[SUP]3[/SUP]Two-letter abbreviation for viral protein.
[/TD]
[/TR]
[/TABLE]
Most infected individuals make neutralizing antibodies against HIV, directed against the envelope glycoprotein. However, the levels of neutralizing activity are low; many anti-envelope antibodies are nonneutralizing. It is believed that the dense glycosylation may inhibit binding of neutralizing antibody to the envelope protein. The envelope glycoprotein shows great sequence variability. This natural variation may allow the evolution of successive populations of resistant virus that escape recognition by existing neutralizing antibodies.
The neutralizing antibodies can be measured in vitro by inhibiting HIV infection of susceptible lymphocyte cell lines. Viral infection is quantified by (1) reverse transcriptase assay, which measures the enzyme activity of released HIV particles; (2) indirect immunofluorescence assay, which measures the percentage of infected cells; and (3) reverse transcriptase-polymerase chain reaction (RT-PCR) or branched-chain DNA (bDNA) amplification assays that measure HIV nucleic acids.
Cellular responses develop that are directed against HIV proteins. Cytotoxic T lymphocytes (CTLs) recognize env, pol, gag, and nef gene products; this reactivity is mediated by major histocompatibility complex-restricted CD3–CD8 lymphocytes. The env-specific reactivity occurs in nearly all infected people and decreases with progression of disease. Natural killer (NK) cell activity has also been detected against HIV-1 gp120.
It is not clear which host responses are important in providing protection against HIV infection or development of disease. A problem confronting AIDS vaccine research is that the correlates of protective immunity are not known, including the relative importance of humoral and cell-mediated immune responses.
Laboratory Diagnosis
Evidence of infection by HIV can be detected in three ways: (1) virus isolation, (2) serologic determination of antiviral antibodies, and (3) measurement of viral nucleic acid or antigens.
Virus Isolation
HIV can be cultured from lymphocytes in peripheral blood (and occasionally from specimens from other sites). The numbers of circulating infected cells vary with the stage of disease (Figure 44–5). Higher titers of virus are found in the plasma and in peripheral blood cells of patients with AIDS as compared with asymptomatic individuals. The magnitude of plasma viremia appears to be a better correlate of the clinical stage of HIV infection than the presence of any antibodies (Figure 44–7). The most sensitive virus isolation technique is to cocultivate the test sample with uninfected, mitogen-stimulated peripheral blood mononuclear cells. Primary isolates of HIV grow very slowly compared with laboratory-adapted strains. Viral growth is detected by testing culture supernatant fluids after about 7–14 days for viral reverse transcriptase activity or for virus-specific antigens (p24).

[TABLE="width: 100%"] [TR] [TD]Figure 44–7.

[/TD]
[/TR]
[TR]
[TD][TABLE="width: 100%"]
[TR]
[TD="align: center"]

[/TD]
[/TR]
[TR]
[TD="class: font11"]Pattern of HIV antibody responses related to the course of HIV infection. (PBL, peripheral blood lymphocytes; CTL, cytotoxic T lymphocytes.)
(Reproduced, with permission, from Weiss RA: How does HIV cause AIDS? Science 1993;260:1273.)
[/TD]
[/TR]
[/TABLE]
[/TD]
[/TR]
[/TABLE]
The vast majority of HIV-1 antibody-positive persons will have virus that can be cultured from their blood cells. However, virus isolation techniques are time-consuming and laborious and are limited to research studies. PCR amplification techniques are more commonly used for detection of virus in clinical specimens.
Serology
Test kits are commercially available for measuring antibodies by enzyme-linked immunoassay (EIA). If properly performed, these tests have a sensitivity and specificity exceeding 98%. When EIA-based antibody tests are used for screening populations with a low prevalence of HIV infections (eg, blood donors), a positive test in a serum sample must be confirmed by a repeat test. If the repeat EIA test is reactive, a confirmation test is performed to rule out false-positive EIA results. The most widely used confirmation assay is the Western blot technique, in which antibodies to HIV proteins of specific molecular weights can be detected. Antibodies to viral core protein p24 or envelope glycoproteins gp41, gp120, or gp160 are most commonly detected.
The response pattern against specific viral antigens changes over time as patients progress to AIDS. Antibodies to the envelope glycoproteins (gp41, gp120, gp160) are maintained, but those directed against the Gag proteins (p17, p24, p55) decline. The decline of anti-p24 may herald the beginning of clinical signs and other immunologic markers of progression (Figure 44–7).
Simple, rapid tests for detecting HIV antibodies are available for use in laboratories ill-equipped to perform EIA tests and in settings where test results are desired with little delay. The simple tests can be performed on blood or oral fluid and are based on principles such as particle agglutination or immunodot reactions. The most recent developments are rapid tests that can detect HIV antibodies in whole blood specimens that require no processing. These tests can be performed outside the traditional laboratory setting.
Home testing kits are available. The procedure involves placing drops of blood from a finger prick on a specially treated card. The card is then mailed to a licensed laboratory for testing.
The mean time to seroconversion after HIV infection is 3–4 weeks. Most individuals will have detectable antibodies within 6–12 weeks after infection, whereas virtually all will be positive within 6 months. HIV infection for longer than 6 months without a detectable antibody response is very uncommon.
Detection of Viral Nucleic Acid or Antigens
Amplification assays such as the RT-PCR, DNA PCR, and bDNA tests are commonly used to detect viral RNA in clinical specimens. The RT-PCR assay uses an enzymatic method to amplify HIV RNA; the bDNA assay amplifies viral RNA by sequential oligonucleotide hybridization steps. The tests can be quantitative when reference standards are used; appropriate positive and negative controls must be included with each test. These molecular-based tests are very sensitive and form the basis for plasma viral load determinations. HIV sequence heterogeneity may limit the sensitivity of these assays to detect HIV infections. The HIV RNA levels are important predictive markers of disease progression and valuable tools with which to monitor the effectiveness of antiviral therapies.
Early diagnosis of HIV infection in infants born to infected mothers can be accomplished using plasma HIV-1 RNA tests. The presence of maternal antibodies makes serologic tests uninformative.
Low levels of circulating HIV-1 p24 antigen can be detected in the plasma by EIA soon after infection. The antigen often becomes undetectable after antibodies develop (because the p24 protein is complexed with p24 antibodies) but may reappear late in the course of infection, indicating a poor prognosis.
Epidemiology
Worldwide Spread of AIDS
AIDS was first recognized in the United States in 1981 as a new disease entity in homosexual men. Twenty years later, AIDS had become a worldwide epidemic that continues to expand. The Joint United Nations Program on HIV/AIDS estimated that by the end of 2005, a total of 39 million people worldwide were living with HIV/AIDS, the majority having been infected by heterosexual contact (Figure 44–8). It was estimated that in that year, 2.8 million people died of AIDS and that 4 million new infections with HIV occurred, including 500,000 babies infected perinatally. By the year 2005, the World Health Organization estimated that more than 25 million people worldwide had died of AIDS and that over 15 million children had been orphaned, 12 million of whom were living in sub-Saharan Africa.

[TABLE="width: 100%"] [TR] [TD]Figure 44–8.

[/TD]
[/TR]
[TR]
[TD][TABLE="width: 100%"]
[TR]
[TD="align: center"]

[/TD]
[/TR]
[TR]
[TD="class: font11"]Adults and children estimated to be living with HIV/AIDS, by continent or region, as of December 2005. It is estimated that about 2.8 million people worldwide died of HIV/AIDS in 2005.
(Data from the Joint United Nations Program on HIV/AIDS.)
[/TD]
[/TR]
[/TABLE]
[/TD]
[/TR]
[/TABLE]
The epidemic varies by geographic region. Based on 2005 data, sub-Saharan Africa had the highest number of HIV infections (Figure 44–8). In certain high-prevalence cities in Africa, as many as one of every three adults was infected with the virus. Infections were spreading also in southern and southeastern Asia (especially in India, China, and Russia). Because AIDS tends to strike young adults and workers in their prime, the AIDS epidemic is having devastating effects on social and economic structures in some countries.
Group M viruses are responsible for most HIV-1 infections worldwide, but subtype distributions vary. Subtype C predominates in southern Africa, subtype A in West Africa, and subtype B in the United States, Europe, and Australia. HIV-2 has remained localized primarily to West Africa.
The World Health Organization estimates that of the 4 million new HIV infections each year, 90% are occurring in developing countries. In those countries, AIDS is overwhelmingly a heterosexually transmitted disease, and there are about equal numbers of male and female cases.
It is hypothesized that the rapid dissemination of HIV globally in the latter part of the 20th century was fostered by massive migration of rural inhabitants to urban centers, coupled with international movement of infected individuals as a consequence of civil disturbances, tourism, and business travels.
United States
The face of the AIDS epidemic has changed in the United States since 1981. At first, most of the cases occurred in homosexual men. Then the disease was identified in injecting drug users. By 2005, racial and ethnic minority communities were disproportionately affected, accounting for about two-thirds of reported HIV/AIDS cases. Heterosexual transmission was increasingly more common, and about one-quarter of new diagnoses were in women. Most heterosexually acquired AIDS cases were attributed to sexual contact with an injecting drug user or a partner with HIV infection.
By the end of 2005, over 1.5 million HIV/AIDS cases were estimated to have occurred (of which over 500,000 had resulted in death). Over 1 million persons are living with HIV/AIDS in the United States, and an estimated 40,000 new cases occur each year. The death rate decreased for the first time in 1996, reflecting the use of antiretroviral combination therapy and prevention of secondary opportunistic infections.
Pediatric AIDS increased as the number of HIV-infected women increased. It was estimated that 1650 newborns acquired the virus in 1991 in the United States. The numbers of new infections have been reduced dramatically by the development in 1994 of zidovudine antenatal, intrapartum, and neonatal therapy (see below). From transmission rates of 25–30% with no interventions, drug treatments have reduced transmission rates in the United States to less than 2%. There were only about 50 reported cases of pediatric AIDS in 2004. Mother-to-child transmission continues to occur because of undiagnosed HIV infection in the mother and lack of medical treatment.
The success in reducing perinatal HIV transmission in the United States has not been achieved in many poorer countries. Especially in sub-Saharan Africa, mother-to-child transmission rates remain high.
Routes of Transmission
High titers of HIV are found in two body fluids—blood and semen. HIV is transmitted during sexual contact (including genital-oral sex), through parenteral exposure to contaminated blood or blood products, and from mother to child during the perinatal period. The presence of other sexually transmitted diseases such as syphilis, gonorrhea, or herpes simplex type 2 increases the risk of sexual HIV transmission as much as a hundredfold because the inflammation and sores facilitate the transfer of HIV across mucosal barriers. Asymptomatic virus-positive individuals can transmit the virus. Since the first description of AIDS, promiscuous homosexual activity has been recognized as a major risk factor for acquisition of the disease. The risk increases in proportion to the number of sexual encounters with different partners.
Transfusion of infectious blood or blood products is an effective route for viral transmission. For example, over 90% of hemophiliac recipients of contaminated clotting factor concentrates in the United States (before HIV was detected) developed antibodies to HIV. Injection users of illicit drugs are commonly infected through the use of contaminated needles. Injection drug use accounts for a substantial proportion of new AIDS cases.
Careful testing is necessary to ensure a safe blood supply. The World Health Organization has reported that voluntary unremunerated blood donation is far safer than paid donations. It was reported in 1996 that the risk of transfusion-transmitted HIV infection in the United States was very small (about 1:500,000).
Mother-to-infant transmission rates vary from 13% to 40% in untreated women. Infants can become infected in utero, during the birth process, or, more commonly, through breastfeeding. In the absence of breastfeeding, about 30% of infections occur in utero and 70% during delivery. Data indicate that from one-third to one-half of perinatal HIV infections in Africa are due to breastfeeding. Transmission during breastfeeding usually occurs early (by 6 months). High maternal viral loads are a risk factor for transmission.
Health care workers have been infected by HIV following a needlestick with contaminated blood. The numbers of infections are relatively few in comparison with the number of needlesticks that have occurred involving contaminated blood (estimated risk of transmission is about 0.3%). The risk of transmission is even lower after a mucous membrane exposure to infected blood (about 0.09%).
The routes of transmission (blood, sex, and birth) described above account for almost all HIV infections. There has been considerable concern that in rare circumstances other types of transmission may occur, such as through "casual" contact with HIV-infected persons or insect vectors, but there is no evidence of virus transmission under these casual conditions.
Prevention, Treatment, & Control
Antiviral Drugs
A growing number of antiviral drugs are approved for treatment of HIV infections (see Chapter 30). Classes of drugs include both nucleoside and nonnucleoside inhibitors of the viral enzyme reverse transcriptase and inhibitors of the viral protease enzyme. The protease inhibitors are potent antiviral drugs because the protease activity is absolutely essential for production of infectious virus, and the viral enzyme is distinct from human cell proteases. The newest class of drugs—fusion inhibitors first approved in 2003—blocks virus entry into cells.
Therapy with combinations of antiretroviral drugs, referred to as highly active antiretroviral therapy (HAART), became available in 1996. It oftentimes can suppress viral replication to below limits of detection in plasma, decrease viral loads in lymphoid tissues, allow the recovery of immune responses to opportunistic pathogens, and prolong patient survival. However, HAART has failed to cure HIV-1 infections. The virus persists in reservoirs of long-lived, latently infected cells, including memory CD4 T cells. When HAART is discontinued or there is treatment failure, virus production rebounds.
Whereas monotherapy usually results in the rapid emergence of drug-resistant mutants of HIV, combination therapy, which targets multiple steps in virus replication, usually delays selection of HIV mutants. However, mutants that arise which are resistant to one protease inhibitor are often resistant to other protease inhibitors as well.
Transmission of drug-resistant variants may affect future therapy options. In 2004 and 2005, treatment-naïve patients with newly diagnosed HIV infections were found to carry virus with drug-resistant mutations in 8% and 10% of cases in the United States and Europe, respectively. Among perinatally infected infants in the United States in 2002, 19% had virus with drug-resistant mutations.
Results with combination therapy have been successful and have turned HIV infection into a chronic, treatable disease. Prolonged suppression of viral replication can be achieved, along with restoration of immune function. However, additional drug development is needed. Current drug regimens are often complicated and expensive, cannot be tolerated by all patients, have toxic side effects (including lipodystrophy), and lead to a number of treatment failures. The first once-daily pill that combines three HIV drugs was approved in the United States in 2006. The majority of infected persons worldwide do not have access to any HIV drugs.
Zidovudine (azidothymidine; AZT) can significantly reduce the transmission of HIV from mother to infant. A regimen of AZT therapy of the mother during pregnancy and during the birth process and of the baby after birth reduced the risk of perinatal transmission by 65–75% (from about 25% to less than 2%). This treatment decreases vertical transmission at all levels of maternal viral load. A shorter course of AZT given to infected mothers or a simple nevirapine regimen has been shown to reduce transmission by 50% and to be safe for use in developing nations. However, the high rate of HIV transmission by breastfeeding can undermine the benefits of maternal perinatal drug treatment.
Vaccines Against HIV
A safe and effective vaccine offers the best hope of controlling the worldwide AIDS epidemic. As of 2006, many candidate vaccines are under development and are in different stages of testing. Viral vaccines are typically preventive, ie, given to uninfected individuals to prevent either infection or disease. Consideration is also being given to the possibility of therapeutic HIV vaccines, whereby HIV-infected individuals would be treated to boost anti-HIV immune responses, decrease the numbers of virus-infected cells, or delay the onset of AIDS. Vaccine development is difficult because HIV mutates rapidly, is not expressed in all cells that are infected, and is not completely cleared by the host immune response after primary infection. HIV isolates show a marked variation, especially in the envelope antigens—variability that probably promotes the emergence of neutralization-resistant mutants. As the correlates of protective immunity are not known, it is unclear what immune responses a vaccine should elicit.
Because of the safety concerns, vaccines based on attenuated or inactivated HIV or on simian isolates are viewed with apprehension. Recombinant viral proteins—especially those of the envelope glycoproteins—are likely candidates, whether delivered with adjuvants or with heterologous viral vectors. Many novel vaccination methods are also under investigation. Gene therapy approaches are being developed that are designed to achieve "intracellular immunization," ie, to genetically alter target cells in such a way as to make them resistant to HIV.
A large hurdle for vaccine development is the lack of an appropriate animal model for HIV. Chimpanzees are the only animals that are susceptible to HIV. Not only is the supply scarce, but chimpanzees develop only viremia and antibodies; they do not develop immunodeficiency. The SIV-macaque model of simian AIDS does develop disease and is useful for vaccine development studies.
Control Measures
Without control by drugs or vaccines, the only way to avoid epidemic spread of HIV is to maintain a lifestyle that minimizes or eliminates the high-risk factors discussed above. No cases have been documented to result from such common exposures as sneezing, coughing, sharing meals, or other casual contacts.
Because HIV may be transmitted in blood, all donor blood should be tested for antibody. Properly conducted antibody tests appear to detect almost all HIV-1 and HIV-2 carriers. In settings with widespread screening of blood donors for viral exposure and the rejection of contaminated blood, transmission by blood transfusion has virtually disappeared.
Public health authorities have recommended that persons reported to have an HIV infection be given the following information and advice:
(1) Almost all persons will remain infected for life and will develop the disease.
(2) Although asymptomatic, such individuals may transmit HIV to others. Regular medical evaluation and follow-up are advised.
(3) Infected persons should refrain from donating blood, plasma, body organs, other tissues, or sperm.
(4) There is a risk of infecting others by sexual intercourse (vaginal or anal), by oral-genital contact, or by sharing of needles. The consistent and proper use of condoms can reduce transmission of the virus, though protection is not absolute.
(5) Toothbrushes, razors, and other implements that could become contaminated with blood should not be shared.
(6) Seropositive women or women with seropositive sexual partners are themselves at increased risk of acquiring AIDS. If they become pregnant, their offspring also are at high risk of acquiring AIDS.
(7) After accidents that result in bleeding, contaminated surfaces should be cleaned with household bleach freshly diluted 1:10 in water.
(8) Devices that have punctured the skin—eg, hypodermic and acupuncture needles—should be steam-sterilized by autoclaving before reuse or should be safely discarded. Dental instruments should be heat-sterilized between patients. Whenever possible, disposable needles and equipment should be used.
(9) When seeking medical or dental care for intercurrent illness, infected persons should inform those responsible for their care that they are seropositive, so that appropriate evaluation can be undertaken and precautions taken to prevent transmission to others.
(10) Testing for HIV antibody should be offered to persons who may have been infected as a result of their contact with seropositive individuals (eg, sexual partners, persons with whom needles have been shared, infants born to seropositive mothers).
(11) Most persons with a positive test for HIV do not need to consider a change in employment unless their work involves significant potential for exposing others to their blood or other body fluids. There is no evidence of HIV transmission by food handling.
(12) Seropositive persons in the health care professions who perform invasive procedures or have skin lesions should take precautions similar to those recommended for hepatitis B carriers to protect patients from the risk of infection.
(13) Children with positive tests should be allowed to attend school, since casual person-to-person contact of schoolchildren poses no risk. However, a more restricted environment is advisable for preschool children or children who lack control of their body secretions, display biting behavior, or have oozing lesions.
Health Education
Without a vaccine or treatment, the prevention of cases of AIDS relies on the success of education projects involving behavioral changes. The health education messages for the general public have been summarized as follows: (1) Any sexual intercourse (outside of mutually monogamous HIV antibody-negative relationships) should be protected by a condom. (2) Do not share unsterile needles or syringes. (3) All women who have been potentially exposed should seek HIV antibody testing before becoming pregnant and, if the test is positive, should consider avoiding pregnancy. (4) HIV-infected mothers should avoid breast feeding to reduce transmission of the virus to their children if safe alternative feeding options are available.
[/TD]
[/TR]
[/TABLE]

[TD="bgcolor: #ffffff"]References
[TABLE="width: 100%"]
[TR]
[TD="class: contentBody"]Apetrei C, Robertson DL, Marx PA: The history of SIVs and AIDS: Epidemiology, phylogeny, and biology of isolates from naturally SIV infected non-human primates (NHP) in Africa. Front in Biosci 2004;9:225. [PMID: 14766362]

[/TD]

[TD="class: contentBody"]Desrosiers RC: Nonhuman lentiviruses. In: Fields Virology, 4th ed. Knipe DM et al (editors). Lippincott Williams & Wilkins, 2001.

[/TD]

[TD="class: contentBody"]Dybul M et al (editors): Guidelines for using antiretroviral agents among HIV-infected adults and adolescents: The Panel on Clinical Practices for HIV. Ann Intern Med 2002;137:381. [PMID: 12617573]

[/TD]

[TD="class: contentBody"]Freed EO, Martin MA: HIVs and their replication. In: Fields Virology, 4th ed. Knipe DM et al (editors). Lippincott Williams & Wilkins, 2001.

[/TD]

[TD="class: contentBody"]Hahn BH et al: AIDS as a zoonosis: Scientific and public health implications. Science 2000;287:607. [PMID: 10649986]

[/TD]

[TD="class: contentBody"]Moore JP, Doms RW: The entry of entry inhibitors: A fusion of science and medicine. Proc Natl Acad Sci U S A 2003;100: 10598. [PMID: 12960367]

[/TD]

[TD="class: contentBody"]Patrick MK, Johnston JB, Power C: Lentiviral neuropathogenesis: Comparative neuroinvasion, neurotropism, neurovirulence, and host neurosusceptibility. J Virol 2002;76:7923. [PMID: 12133996]

[/TD]

[TD="class: contentBody"]Paul ME, Schearer WT: Pediatric human immunodeficiency virus infection. In: Pediatric Allergy: Principles and Practice . Leung DYM, Sampson HA, Geha RS, Szefler SJ (editors). Mosby, 2003.

[/TD]

[TD="class: contentBody"]Schreiber GB et al: The risk of transfusion-transmitted viral infections. N Engl J Med 1996;334:1685. [PMID: 8637512]

[/TD]

[TD="class: contentBody"]Sepkowitz KA: AIDS—the first 20 years. N Engl J Med 2001;344: 1764.

[/TD]

[TD="class: contentBody"]Twenty-five years of HIV/AIDS—United States, 1981–2006. MMWR Morb Mortal Wkly Rep 2006;55 (No. 21).

[/TD]

[TD="class: contentBody"]U.S. Public Health Service guidelines for testing and counseling blood and plasma donors for human immunodeficiency virus type 1 antigen. MMWR Morb Mortal Wkly Rep 1996;45 (RR-2).

[/TD]

[TD="class: contentBody"]Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Morb Mortal Wkly Rep 2005;54(RR-9[/TD]

[/TD]
[/TR]
[/TABLE]

 

[cute b]

Nimegundua kitu....
Mama yangu mdogo aliugua sana miaka 10 iliyopita na alivyozidiwa akaamua kufanyiwa vipimo na akaambiwa ana HIV+ Wakati huo alikuwa ananyonyesha mtoto mwenye miaka miwili na ana mume....
Akaambiwa aende na mume wake na mtoto wote wakafanyiwa vipimo vituo tofaut tofaut...mtoto ni HIV- Na mume pia ni HIV-. Basi mama akakubaliana na hali.
Leo ni mwaka wa kumi dawa zile anatumia siku akiamua na anakunywa pombe sana tena hadi piwa anakunywa na anaweza akagoma kumeza dawa hadi wiki mbili na akinywa pombe hawezi kula chakula yaani kila anayemwona lazma amsikitikie....
Lakini cha ajabu sasa hajawahi kuumwa akalazwa hospital akiugua ni malaria kama watu wengine na sio mara kwa mara.....
Na pia hajawahi kupata matunzo kama wanavyoshauriwa hospital wale vyakula vya aina flan yeye kila kitu anakula..
Na akipumzika kunywa pombe ni chapa kazi sana na kulima analima.
Sasa mimi huwa najiuliza huu ni UKIMWI ambao nilikuwa nasikia unaua enzi hizo za unaitwa juliana huko kagera kwa kweli sidhan..
Yawezekana ikawa ni imani tuu lakini wenyew haupo...sema mtu ukishapima ukapewa majibu kuwa unao kinachokuua ni mawazo tuu..
Nimewahi kuambiwa pia na mtaalam wa Afya mmoja kwamba UGONJWA ULIOUA SANA MIAKA YA 80 ,90 AMBAO BAADA YA TAFITI NDIO UKAITWA UKIMWI ULIKUWA NI MLIPUKO WA MAGONJWA TUU KAMA MAGONJWA MENGINE NA HAUENDANI NA HUU BAADA YA TAFITI...
Ila daah if haupo kweli basi wazungu sio watu wazuri nipate tuu nauli nikaish huko kwao wasije niua presha bure..

 

[ngota wa nzambe]

Kaka, antibody ziko specific for a certain infection...yaani kwa maana kila ugonjwa unakuwa na antibody specific to it..specific antibody to HIV ni tofauti sana na specific antibody to other viral infections

 

[Deception]

yote ulioyandika ni uongo. mimi ni mwalimu wa chuo cha muhimbili kwenye sayansi za maabara. HIV ipo, unaweza kuisolate hata wewe ukifundishwa na pia vipimovyote ni kweli na sio imani. asikudanganye mtu na hizo articles unazosoma na za medical fanatics na fallacy. jaribu kusoma articles toka HINARI, PUBMED na WHO utapa articles zenye ukweli na in depth knowledge

1. mimi ni mwalimu wa chuo cha muhimbili...

Nimefurahi sana sasa najadiliana na mwalimu.Hapa sasa nataka watu wajionee wenyewe kitakachotokea.

2.yote ulioyandika ni uongo..

Sasa unatakiwa kuthibitisha ni wapi nimesema uongo.Kusema tu kwamba mimi ni muongo haisaidii kitu,haiwasaidii watu kuelewa dhana hii.Thibitisha.Wewe ni mwalimu,hivyo unatakiwa uwe tofauti na wale wengine.

3.unaweza kuisolate hata wewe ukifundishwa...

Siwezi kukupinga kwa kuwa inawezekana hata hujui maana ya ku isolate na ku purify.Mgunduzi mwenyewe amekiri kwamba hawajawahi ku isolate/purify HIV,sasa wewe sijui unawezaje,ndio maana nimesema inawezekana hujui maana ya ku isolate/purify.Labda mwalimu tuambie, ku isolate na ku purify maana yake ni nini kwa jinsi unavyoelewa?

4.HINARI, PUBMED na WHO....

Unasema hawa ndio wanatoa articles zenye ukweli na wale wengine articles zao ni za uongo.Hivi mwalimu unaweza kuwaelezea watu wanaweza kutambua vipi kwamba articles zao ni za ukweli?

Halafu pia ningependa kukujuilisha kwamba wamiliki/viongozi wa hayo mashirika uliyotaja hapo juu ni miongoni mwa wanufaika wa viwanda vya madawa.Sasa usitegemee mtu akaikashifu kazi yake,Je,unalijua hilo?Dig deep mwalimu,bado uko juu juu sana.

Halafu sijui ni kwanini mnapenda sana ku copy na ku paste rundo la maandishi na kuyaweka hapa,je wewe mwalimu hujui kwamba kuna wasiojua kiingereza nao wangependa kujua mambo haya?Halafu kwanini usingeweka link ili wale wanaotaka kufuatilia waingie huko kwenye link,huoni kwamba kuweka link ndio vyema zaidi ya kurundika rundo la maandishi tena ya ku copy,sidhani hata kama wewe mwenyewe uliyasoma hayo yote.

Hata mimi nina articles nyingi tu,pia nina link nyingi tu zenye mambo mazito na maandishi mengi sana zaidi ya hayo yako,pia nina scientific papers nyingi tu,nina video nyingi tu.Na mimi ninge copy na ku paste hapa ingekuwaje?

Nadhani,sina uhakika,ila nadhani unakimbia hoja za msingi.Sasa naweka hoja hapa chini ili majadiliano yetu yalenge kwenye hizo hoja;

1.HIV hasababishi AIDS na haambukizwi kwa njia ya ngono.
2.ARVs hazina faida yoyote mwilini zaidi ya hasara na ndio hizi ARVs zinazoua watu halafu tunasingizia HIV.ARVs husababisha AIDS baada ya kuzitumia kwa muda mrefu.
3.Vipimo vya 'HIV' ni feki/vya uongo,havipimi HIV kwa muonekano.

Tupambanishe hoja zetu hapo.Chagua hoja mojawapo tuanze nayo ambayo kwako unaiona ni rahisi halafu tuanze kazi.

 

[Deception]

Asante sana Mkuu,ndo vile tena tunaomba Mungu tu atusaidie, Mkuu usiombe the so called Aids/HIV liingie kwenye familia yako inatisha sana aiseee!!!! Linarudisha maendeleo nyuma si mchezo maana Hamna kutulia kila siku ni kuhangaika tu, yaani katika miezi hii miwili takriban 8M zimekatika na bado ndo kama hivi yupo hospital tena, somehow imeshake nguvu kazi yangu maana tumekosa kusimamia kazi zetu moja kwa moja tunahangaika na mgonjwa tu,katika miezi hii miwili nimeingia ofisini kwangu mara Nne tu, inabidi nikae na mgonjwa maana huduma zake si mchezo kwa mtu ambaye si wa karibu naye na mwenye moyo hawezi Fanya.

Pole sana kwa matatizo.Ukichunguza matatizo aliyonayo ndugu yako ndio yaleyale niliyosema yanasababishwa na matumizi ya muda mrefu ya ARVs kama ulivyoni quote.Wewe sasa ni umeshuhudia mwenyewe na sasa unaanza kupata picha kamili ya mambo haya.

Kama uko tayari tunaweza kushirikiana kuokoa maisha yake kwa kufanya yafuatayo;

1.Kumuondoa sumu iliyojaa mwilini ambayo ndio sababu ya kisukari alichonacho.Sumu hii imesababishwa na ARVs.
2.Kumpa vyakula/supplements zitakazorudisha virutubisho vilivyopotea mwilini kutokana na sumu ya ARVs kama vile madini ya chuma,calcium nk,vitamini mbalimbali na kurudisha pH ya damu yake katika hali ya kawaida.Hapo alipo lazima pH ya damu yake itakuwa ni 'acidic' zaidi,ukitaka kuamini hili mwambie daktari ampime pH atakwambia,nina uhakika na hilo.

Sasa ukiwa tayari nijulishe.

Angalizo:
Siko kibiashara hapa.Siwezi kumzuia mtu yeyote kufikiria kwamba mimi nafanya biashara,kila mtu ana uhuru wa kufikiri chochote,isitoshe mtu hana uwezo wa ku control fikra zake.

 

[mzee wa kigonzile]

Kwanza watu inabidi wafahamu kuwa baada ya Robert Gallo kuclaim kwamba HIV inasababisha UKIMWI alichokifanya ni kupita mlango wa nyuma kwa kukwepa kiunzi cha PEER REVIEW SCIENCE yaan uthibitisho wa pamoja wa wanasayansi kuthibitisha kwamba HIV ndiyo sababu ya UKIMWI.

Na hakufanya hivyo kwa bahati mbaya, alikuwa anajua anachokifanya kuwa hakiko sahihi, kwasababu huyu huyu Robert Gallo aliwahi kuclaim kuwa retrovirus aina ya HTLV1 wanasababisha kansa kwa binadamu katika miaka ya 70 lakini Peter Duesberg na wanasayansi wengine walikuja na critics, Gallo akashindwa kuthibitisha kuwa HTLV1 ndiyo sababu ya kansa.

Kwahiyo kinachoonekana hapa huyu Gallo alikuwa na kirusi chake tayari ambacho alikuwa akikitafutia ugonjwa wa kuuambatanisha, alijaribu kufanya hivyo kwenye ugonjwa wa kansa akafeli, sasa amekuja kufanikiwa kwenye UKIMWI, lakini amekuja na jina linguine sio HTLV1 tena ni HTLV3 baada ya kumodify cell line za kirusi cha Luc Montagnier ambacho kilijulikana kwa jina la LAV.

Na baada ya kuclaim kwamba HIV ndiyo sababu ya UKIMWI, zile test result zake hazikuwekwa wazi mpaka baada ya wiki moja kupita tangu kuitisha Press Conference na kuutangazia ulimwengu kwamba HIV ndiyo sababu ya UKIMWI. Hazikuwekwa wazi kwasababu alijua wanasayansi wenzake wangekuja na critics sababu alichokifanya ni ulaghai.
Kwahiyo press conference ilifanyika tarehe 23 April, 1984, lakini test results zilikuwa published kwenye science magazine tarehe 4 May, 1984. Na matokeo ya results yalikuwa kama ifuatavyo;

“Only 44 of 93 AIDS patients tested had the virus (LESS THAN HALF) “
Reference on: Science Vol.224 May 4, 1984

Sasa ukitazama hiyo result ya Gallo hapo inaonesha kwamba kati ya wagonjwa 93 wa UKIMWI ambao walikuwa tested ni wagonjwa 44 walikutwa na HIV.

Sasa swali linakuja, wagonjwa 49 waliobaki ambao hawakuwa na HIV, kitu gani ambacho kilisababisha ukimwi kwao?
Na kama HIV ndiyo major role kwenye kusababisha UKIMWI, kwanini hao wagonjwa 49 waliobaki hawakuwa na hiyo HIV?
Tatu kwanini waanzilishi wa nadharia ya HIV/AIDS wame conclude kwamba HIV ndiyo sababu ya UKIMWI wakati zaidi ya nusu ya wagonjwa (Wagonjwa 49) ambao walikuwa tested hawakuwa na hiyo HIV?

YOU CANT FOOL ALL THE PEOPLE ALL THE TIME.

 

[mzee wa kigonzile]

Nimegundua kitu....
Mama yangu mdogo aliugua sana miaka 10 iliyopita na alivyozidiwa akaamua kufanyiwa vipimo na akaambiwa ana HIV+ Wakati huo alikuwa ananyonyesha mtoto mwenye miaka miwili na ana mume....
Akaambiwa aende na mume wake na mtoto wote wakafanyiwa vipimo vituo tofaut tofaut...mtoto ni HIV- Na mume pia ni HIV-. Basi mama akakubaliana na hali.
Leo ni mwaka wa kumi dawa zile anatumia siku akiamua na anakunywa pombe sana tena hadi piwa anakunywa na anaweza akagoma kumeza dawa hadi wiki mbili na akinywa pombe hawezi kula chakula yaani kila anayemwona lazma amsikitikie....
Lakini cha ajabu sasa hajawahi kuumwa akalazwa hospital akiugua ni malaria kama watu wengine na sio mara kwa mara.....
Na pia hajawahi kupata matunzo kama wanavyoshauriwa hospital wale vyakula vya aina flan yeye kila kitu anakula..
Na akipumzika kunywa pombe ni chapa kazi sana na kulima analima.
Sasa mimi huwa najiuliza huu ni UKIMWI ambao nilikuwa nasikia unaua enzi hizo za unaitwa juliana huko kagera kwa kweli sidhan..
Yawezekana ikawa ni imani tuu lakini wenyew haupo...sema mtu ukishapima ukapewa majibu kuwa unao kinachokuua ni mawazo tuu..
Nimewahi kuambiwa pia na mtaalam wa Afya mmoja kwamba UGONJWA ULIOUA SANA MIAKA YA 80 ,90 AMBAO BAADA YA TAFITI NDIO UKAITWA UKIMWI ULIKUWA NI MLIPUKO WA MAGONJWA TUU KAMA MAGONJWA MENGINE NA HAUENDANI NA HUU BAADA YA TAFITI...
Ila daah if haupo kweli basi wazungu sio watu wazuri nipate tuu nauli nikaish huko kwao wasije niua presha bure..

Ni kweli Mkuu, ila sio kila mzungu ni mtu mbaya. Mtu wa kwanza ku question hii hypothesis si mtu mweusi na white man pia. Lakini nataka nikwambie kitu kimoja siyo kila mtu mweupe anafurahishwa na hii, na wapo ambao wamezunguza kwenye media kabisa na nukuu zao zipo na zitaendelea kuwepo wakisema HIV/AIDS ni moja ya dhambi kubwa kufanywa na wanasanyansi katika huu ulimwengu. Na ndiyo maana wanashindwa kukaa kimya mbele hii dhambi, wanapaza sauti lakini sauti zinazimwa na politica power.

 

[pakamwam]

1. mimi ni mwalimu wa chuo cha muhimbili...Nimefurahi sana sasa najadiliana na mwalimu.Hapa sasa nataka watu wajionee wenyewe kitakachotokea.2.yote ulioyandika ni uongo..Sasa unatakiwa kuthibitisha ni wapi nimesema uongo.Kusema tu kwamba mimi ni muongo haisaidii kitu,haiwasaidii watu kuelewa dhana hii.Thibitisha.Wewe ni mwalimu,hivyo unatakiwa uwe tofauti na wale wengine.3.unaweza kuisolate hata wewe ukifundishwa...Siwezi kukupinga kwa kuwa inawezekana hata hujui maana ya ku isolate na ku purify.Mgunduzi mwenyewe amekiri kwamba hawajawahi ku isolate/purify HIV,sasa wewe sijui unawezaje,ndio maana nimesema inawezekana hujui maana ya ku isolate/purify.Labda mwalimu tuambie, ku isolate na ku purify maana yake ni nini kwa jinsi unavyoelewa?4.HINARI, PUBMED na WHO....Unasema hawa ndio wanatoa articles zenye ukweli na wale wengine articles zao ni za uongo.Hivi mwalimu unaweza kuwaelezea watu wanaweza kutambua vipi kwamba articles zao ni za ukweli?Halafu pia ningependa kukujuilisha kwamba wamiliki/viongozi wa hayo mashirika uliyotaja hapo juu ni miongoni mwa wanufaika wa viwanda vya madawa.Sasa usitegemee mtu akaikashifu kazi yake,Je,unalijua hilo?Dig deep mwalimu,bado uko juu juu sana.Halafu sijui ni kwanini mnapenda sana ku copy na ku paste rundo la maandishi na kuyaweka hapa,je wewe mwalimu hujui kwamba kuna wasiojua kiingereza nao wangependa kujua mambo haya?Halafu kwanini usingeweka link ili wale wanaotaka kufuatilia waingie huko kwenye link,huoni kwamba kuweka link ndio vyema zaidi ya kurundika rundo la maandishi tena ya ku copy,sidhani hata kama wewe mwenyewe uliyasoma hayo yote.Hata mimi nina articles nyingi tu,pia nina link nyingi tu zenye mambo mazito na maandishi mengi sana zaidi ya hayo yako,pia nina scientific papers nyingi tu,nina video nyingi tu.Na mimi ninge copy na ku paste hapa ingekuwaje?Nadhani,sina uhakika,ila nadhani unakimbia hoja za msingi.Sasa naweka hoja hapa chini ili majadiliano yetu yalenge kwenye hizo hoja;1.HIV hasababishi AIDS na haambukizwi kwa njia ya ngono.2.ARVs hazina faida yoyote mwilini zaidi ya hasara na ndio hizi ARVs zinazoua watu halafu tunasingizia HIV.ARVs husababisha AIDS baada ya kuzitumia kwa muda mrefu.3.Vipimo vya 'HIV' ni feki/vya uongo,havipimi HIV kwa muonekano.Tupambanishe hoja zetu hapo.Chagua hoja mojawapo tuanze nayo ambayo kwako unaiona ni rahisi halafu tuanze kazi.

sipo kwa ajili ya kupambana.somaarticle niliyokutumia hapoo juu. utaelewa ninachokisema ni nini. unatakiwa kuelewa hili. pia naomba uache kudanganya watuuuuLaboratory DiagnosisEvidence of infection by HIV can be detected in three ways: (1) virus isolation, (2) serologic determination of antiviral antibodies, and (3) measurement of viral nucleic acid or antigens.Virus IsolationHIV can be cultured from lymphocytes in peripheral blood (and occasionally from specimens from other sites). The numbers of circulating infected cells vary with the stage of disease (Figure 44–5). Higher titers of virus are found in the plasma and in peripheral blood cells of patients with AIDS as compared with asymptomatic individuals. The magnitude of plasma viremia appears to be a better correlate of the clinical stage of HIV infection than the presence of any antibodies (Figure 44–7). The most sensitive virus isolation technique is to cocultivate the test sample with uninfected, mitogen-stimulated peripheral blood mononuclear cells. Primary isolates of HIV grow very slowly compared with laboratory-adapted strains. Viral growth is detected by testing culture supernatant fluids after about 7–14 days for viral reverse transcriptase activity or for virus-specific antigens (p24).Figure 44–7. Pattern of HIV antibody responses related to the course of HIV infection. (PBL, peripheral blood lymphocytes; CTL, cytotoxic T lymphocytes.)(Reproduced, with permission, from Weiss RA: How does HIV cause AIDS? Science 1993;260:1273.) The vast majority of HIV-1 antibody-positive persons will have virus that can be cultured from their blood cells. However, virus isolation techniques are time-consuming and laborious and are limited to research studies. PCR amplification techniques are more commonly used for detection of virus in clinical specimens.SerologyTest kits are commercially available for measuring antibodies by enzyme-linked immunoassay (EIA). If properly performed, these tests have a sensitivity and specificity exceeding 98%. When EIA-based antibody tests are used for screening populations with a low prevalence of HIV infections (eg, blood donors), a positive test in a serum sample must be confirmed by a repeat test. If the repeat EIA test is reactive, a confirmation test is performed to rule out false-positive EIA results. The most widely used confirmation assay is the Western blot technique, in which antibodies to HIV proteins of specific molecular weights can be detected. Antibodies to viral core protein p24 or envelope glycoproteins gp41, gp120, or gp160 are most commonly detected.The response pattern against specific viral antigens changes over time as patients progress to AIDS. Antibodies to the envelope glycoproteins (gp41, gp120, gp160) are maintained, but those directed against the Gag proteins (p17, p24, p55) decline. The decline of anti-p24 may herald the beginning of clinical signs and other immunologic markers of progression (Figure 44–7).Simple, rapid tests for detecting HIV antibodies are available for use in laboratories ill-equipped to perform EIA tests and in settings where test results are desired with little delay. The simple tests can be performed on blood or oral fluid and are based on principles such as particle agglutination or immunodot reactions. The most recent developments are rapid tests that can detect HIV antibodies in whole blood specimens that require no processing. These tests can be performed outside the traditional laboratory setting.Home testing kits are available. The procedure involves placing drops of blood from a finger prick on a specially treated card. The card is then mailed to a licensed laboratory for testing.The mean time to seroconversion after HIV infection is 3–4 weeks. Most individuals will have detectable antibodies within 6–12 weeks after infection, whereas virtually all will be positive within 6 months. HIV infection for longer than 6 months without a detectable antibody response is very uncommon.Detection of Viral Nucleic Acid or AntigensAmplification assays such as the RT-PCR, DNA PCR, and bDNA tests are commonly used to detect viral RNA in clinical specimens. The RT-PCR assay uses an enzymatic method to amplify HIV RNA; the bDNA assay amplifies viral RNA by sequential oligonucleotide hybridization steps. The tests can be quantitative when reference standards are used; appropriate positive and negative controls must be included with each test. These molecular-based tests are very sensitive and form the basis for plasma viral load determinations. HIV sequence heterogeneity may limit the sensitivity of these assays to detect HIV infections. The HIV RNA levels are important predictive markers of disease progression and valuable tools with which to monitor the effectiveness of antiviral therapies.Early diagnosis of HIV infection in infants born to infected mothers can be accomplished using plasma HIV-1 RNA tests. The presence of maternal antibodies makes serologic tests uninformative.Low levels of circulating HIV-1 p24 antigen can be detected in the plasma by EIA soon after infection. The antigen often becomes undetectable after antibodies develop (because the p24 protein is complexed with p24 antibodies) but may reappear late in the course of infection, indicating a poor prognosis.Laboratory DiagnosisEvidence of infection by HIV can be detected in three ways: (1) virus isolation, (2) serologic determination of antiviral antibodies, and (3) measurement of viral nucleic acid or antigens.Virus IsolationHIV can be cultured from lymphocytes in peripheral blood (and occasionally from specimens from other sites). The numbers of circulating infected cells vary with the stage of disease (Figure 44–5). Higher titers of virus are found in the plasma and in peripheral blood cells of patients with AIDS as compared with asymptomatic individuals. The magnitude of plasma viremia appears to be a better correlate of the clinical stage of HIV infection than the presence of any antibodies (Figure 44–7). The most sensitive virus isolation technique is to cocultivate the test sample with uninfected, mitogen-stimulated peripheral blood mononuclear cells. Primary isolates of HIV grow very slowly compared with laboratory-adapted strains. Viral growth is detected by testing culture supernatant fluids after about 7–14 days for viral reverse transcriptase activity or for virus-specific antigens (p24).Figure 44–7. Pattern of HIV antibody responses related to the course of HIV infection. (PBL, peripheral blood lymphocytes; CTL, cytotoxic T lymphocytes.)(Reproduced, with permission, from Weiss RA: How does HIV cause AIDS? Science 1993;260:1273.) The vast majority of HIV-1 antibody-positive persons will have virus that can be cultured from their blood cells. However, virus isolation techniques are time-consuming and laborious and are limited to research studies. PCR amplification techniques are more commonly used for detection of virus in clinical specimens.SerologyTest kits are commercially available for measuring antibodies by enzyme-linked immunoassay (EIA). If properly performed, these tests have a sensitivity and specificity exceeding 98%. When EIA-based antibody tests are used for screening populations with a low prevalence of HIV infections (eg, blood donors), a positive test in a serum sample must be confirmed by a repeat test. If the repeat EIA test is reactive, a confirmation test is performed to rule out false-positive EIA results. The most widely used confirmation assay is the Western blot technique, in which antibodies to HIV proteins of specific molecular weights can be detected. Antibodies to viral core protein p24 or envelope glycoproteins gp41, gp120, or gp160 are most commonly detected.The response pattern against specific viral antigens changes over time as patients progress to AIDS. Antibodies to the envelope glycoproteins (gp41, gp120, gp160) are maintained, but those directed against the Gag proteins (p17, p24, p55) decline. The decline of anti-p24 may herald the beginning of clinical signs and other immunologic markers of progression (Figure 44–7).Simple, rapid tests for detecting HIV antibodies are available for use in laboratories ill-equipped to perform EIA tests and in settings where test results are desired with little delay. The simple tests can be performed on blood or oral fluid and are based on principles such as particle agglutination or immunodot reactions. The most recent developments are rapid tests that can detect HIV antibodies in whole blood specimens that require no processing. These tests can be performed outside the traditional laboratory setting.Home testing kits are available. The procedure involves placing drops of blood from a finger prick on a specially treated card. The card is then mailed to a licensed laboratory for testing.The mean time to seroconversion after HIV infection is 3–4 weeks. Most individuals will have detectable antibodies within 6–12 weeks after infection, whereas virtually all will be positive within 6 months. HIV infection for longer than 6 months without a detectable antibody response is very uncommon.Detection of Viral Nucleic Acid or AntigensAmplification assays such as the RT-PCR, DNA PCR, and bDNA tests are commonly used to detect viral RNA in clinical specimens. The RT-PCR assay uses an enzymatic method to amplify HIV RNA; the bDNA assay amplifies viral RNA by sequential oligonucleotide hybridization steps. The tests can be quantitative when reference standards are used; appropriate positive and negative controls must be included with each test. These molecular-based tests are very sensitive and form the basis for plasma viral load determinations. HIV sequence heterogeneity may limit the sensitivity of these assays to detect HIV infections. The HIV RNA levels are important predictive markers of disease progression and valuable tools with which to monitor the effectiveness of antiviral therapies.Early diagnosis of HIV infection in infants born to infected mothers can be accomplished using plasma HIV-1 RNA tests. The presence of maternal antibodies makes serologic tests uninformative.Low levels of circulating HIV-1 p24 antigen can be detected in the plasma by EIA soon after infection. The antigen often becomes undetectable after antibodies develop (because the p24 protein is complexed with p24 antibodies) but may reappear late in the course of infection, indicating a poor prognosis.

 

[mzee wa kigonzile]

1. mimi ni mwalimu wa chuo cha muhimbili...

Nimefurahi sana sasa najadiliana na mwalimu.Hapa sasa nataka watu wajionee wenyewe kitakachotokea.

2.yote ulioyandika ni uongo..

Sasa unatakiwa kuthibitisha ni wapi nimesema uongo.Kusema tu kwamba mimi ni muongo haisaidii kitu,haiwasaidii watu kuelewa dhana hii.Thibitisha.Wewe ni mwalimu,hivyo unatakiwa uwe tofauti na wale wengine.

3.unaweza kuisolate hata wewe ukifundishwa...

Siwezi kukupinga kwa kuwa inawezekana hata hujui maana ya ku isolate na ku purify.Mgunduzi mwenyewe amekiri kwamba hawajawahi ku isolate/purify HIV,sasa wewe sijui unawezaje,ndio maana nimesema inawezekana hujui maana ya ku isolate/purify.Labda mwalimu tuambie, ku isolate na ku purify maana yake ni nini kwa jinsi unavyoelewa?

4.HINARI, PUBMED na WHO....

Unasema hawa ndio wanatoa articles zenye ukweli na wale wengine articles zao ni za uongo.Hivi mwalimu unaweza kuwaelezea watu wanaweza kutambua vipi kwamba articles zao ni za ukweli?

Halafu pia ningependa kukujuilisha kwamba wamiliki/viongozi wa hayo mashirika uliyotaja hapo juu ni miongoni mwa wanufaika wa viwanda vya madawa.Sasa usitegemee mtu akaikashifu kazi yake,Je,unalijua hilo?Dig deep mwalimu,bado uko juu juu sana.

Halafu sijui ni kwanini mnapenda sana ku copy na ku paste rundo la maandishi na kuyaweka hapa,je wewe mwalimu hujui kwamba kuna wasiojua kiingereza nao wangependa kujua mambo haya?Halafu kwanini usingeweka link ili wale wanaotaka kufuatilia waingie huko kwenye link,huoni kwamba kuweka link ndio vyema zaidi ya kurundika rundo la maandishi tena ya ku copy,sidhani hata kama wewe mwenyewe uliyasoma hayo yote.

Hata mimi nina articles nyingi tu,pia nina link nyingi tu zenye mambo mazito na maandishi mengi sana zaidi ya hayo yako,pia nina scientific papers nyingi tu,nina video nyingi tu.Na mimi ninge copy na ku paste hapa ingekuwaje?

Nadhani,sina uhakika,ila nadhani unakimbia hoja za msingi.Sasa naweka hoja hapa chini ili majadiliano yetu yalenge kwenye hizo hoja;

1.HIV hasababishi AIDS na haambukizwi kwa njia ya ngono.
2.ARVs hazina faida yoyote mwilini zaidi ya hasara na ndio hizi ARVs zinazoua watu halafu tunasingizia HIV.ARVs husababisha AIDS baada ya kuzitumia kwa muda mrefu.
3.Vipimo vya 'HIV' ni feki/vya uongo,havipimi HIV kwa muonekano.

Tupambanishe hoja zetu hapo.Chagua hoja mojawapo tuanze nayo ambayo kwako unaiona ni rahisi halafu tuanze kazi.

Tatizo mtu anasema ni uongo alafu hataki kuwewa facts mezani. Weka facts watu wajifunze.
Medical expert waliowengi afrika (sio wote) wameshindwa kufikiri kwa fikra zilizo huru but hii sio kosa lao haya ni matokeo ya mfumo wa elimu ambao tumerithi kutoka kwa wakoloni.

Ukienda Afrika ya magharibi kuna Proffesors wamejiunga kwenye vugu vugu la denialists kwasababu hawakutaka kujifungia kwenye box. Walijaribu kuzama na kutafuta facts then wakafanya decision ya kujiunga na vuguvugu.
Tatizo tunaamini elimu hii darasani tu, now dunia ni kijiji, huwezi kuishi kama upo kwenye chupa.

 

[SaidAlly]

Tatizo lama MD wengi wanafikiri ndani ya box.

Yani upungufu wa kinga ya mwili alio nao mke wangu anawezaje kuniambukiza mm?

Hahahah....
Nimeipenda sana hii.
Kumbe ndio maana yake?