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Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Previous names for the virus include human T-lymphotropic virus-III (HTLV-III), lymphadenopathy-associated virus (LAV), and AIDS-associated retrovirus (ARV).[1][2]

Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk. Within these body fluids, HIV is present as both free virus particles and virus within infected immune cells. The three major routes of transmission are unprotected sexual intercourse, contaminated needles and transmission from an infected mother to her baby at birth, or through breast milk. Screening of blood products for HIV in the developed world has largely eliminated transmission through blood transfusions or infected blood products in these countries.

HIV infection in humans is now pandemic. As of January 2006, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) estimate that AIDS has killed more than 25 million people since it was first recognized on December 1, 1981, making it one of the most destructive pandemics in recorded history. In 2005 alone, AIDS claimed an estimated 2.4–3.3 million lives, of which more than 570,000 were children. It is estimated that about 0.6% of the world's living population is infected with HIV.[3] A third of these deaths are occurring in sub-Saharan Africa, retarding economic growth and increasing poverty.[4] According to current estimates, HIV is set to infect 90 million people in Africa, resulting in a minimum estimate of 18 million orphans.[5] Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but routine access to antiretroviral medication is not available in all countries.[6]

HIV primarily infects vital cells in the human immune system such as helper T cells (specifically CD4+ T cells), macrophages and dendritic cells. HIV infection leads to low levels of CD4+ T cells through three main mechanisms: firstly, direct viral killing of infected cells; secondly, increased rates of apoptosis in infected cells; and thirdly, killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections. If untreated, eventually most HIV-infected individuals develop AIDS and die; however about one in ten remain healthy for many years, with no noticeable symptoms.[7] Treatment with anti-retrovirals, where available, increases the life expectancy of people infected with HIV. It is hoped that current and future treatments may allow HIV-infected individuals to achieve a life expectancy approaching that of the general public (see Treatment).

Contents [hide] 1 Origin and discovery 2 Transmission 3 Structure and genome 4 Tropism 5 Replication cycle 5.1 Entry to the cell 5.2 Replication and transcription 5.3 Assembly and release 6 Genetic variability 7 The clinical course of infection 8 HIV test 9 Treatment 10 Epidemiology 11 Alternative hypotheses 12 Proteins Involved in Treatment Infection with HIV-1 is associated with a progressive decrease of the CD4+ T cell count and an increase in viral load. The stage of infection can be determined by measuring the patient's CD4+ T cell count, and the level of HIV in the blood.

The initial infection with HIV generally occurs after transfer of body fluids from an infected person to an uninfected one. The first stage of infection, the primary, or acute infection, is a period of rapid viral replication that immediately follows the individual's exposure to HIV leading to an abundance of virus in the peripheral blood with levels of HIV commonly approaching several million viruses per mL.[71] This response is accompanied by a marked drop in the numbers of circulating CD4+ T cells. This acute viremia is associated in virtually all patients with the activation of CD8+ T cells, which kill HIV-infected cells, and subsequently with antibody production, or seroconversion. The CD8+ T cell response is thought to be important in controlling virus levels, which peak and then decline, as the CD4+ T cell counts rebound to around 800 cells per mL (the normal value is 1200 cells per mL ). A good CD8+ T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate the virus.[72] During this period most individuals (80 to 90%) develop an influenza-like illness with symptoms of fever, malaise, lymphadenopathy, pharyngitis, headache, myalgia, and sometimes a rash.[73] Because of the nonspecific nature of these illnesses, it is often not recognized as a sign of HIV infection. Even if patients go to their doctors or a hospital, they will often be misdiagnosed as having one of the more common infectious diseases with the same symptoms. Consequently, these primary symptoms are not used to diagnose HIV infection as they do not develop in all cases and because many are caused by other more common diseases. However, recognizing the syndrome can be important because the patient is much more infectious during this period.

A strong immune defense reduces the number of viral particles in the blood stream, marking the start of the infection's clinical latency stage. Clinical latency can vary between two weeks and 20 years. During this early phase of infection, HIV is active within lymphoid organs, where large amounts of virus become trapped in the follicular dendritic cells (FDC) network.[74] The surrounding tissues that are rich in CD4+ T cells may also become infected, and viral particles accumulate both in infected cells and as free virus. Individuals who are in this phase are still infectious. During this time, CD4+ CD45RO+ T cells carry most of the proviral load.[75]

When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and infections with a variety of opportunistic microbes appear. The first symptoms often include moderate and unexplained weight loss, recurring respiratory tract infections (such as sinusitis, bronchitis, otitis media, pharyngitis), and oral ulcerations. Common opportunistic infections and tumors, most of which are normally controlled by robust CD4+ T cell-mediated immunity then start to affect the patient. Typically, resistance is lost early on to oral Candida species and to Mycobacterium tuberculosis, which leads to an increased susceptibilty to oral candidiasis (thrush) and tuberculosis. Later, reactivation of latent herpes viruses causes patients to suffer from shingles from Epstein-Barr virus-induced B-cell lymphomas, and from Kaposi's sarcoma, a tumor of endothelial cells that occurs when HIV proteins such as Tat interact with Human Herpesvirus-8. Pneumonia caused by the fungus Pneumocystis jiroveci is common and often fatal. In the final stages of AIDS, infection with cytomegalovirus (another herpes virus) or Mycobacterium avium complex is more prominent. Not all patients with AIDS get all these infections or tumors, and there are other tumors and infections that are less prominent but still significant.

HIV test Main article: HIV test Many HIV-positive people are unaware that they are infected with the virus.[76] For example, less than 1% of the sexually active urban population in Africa have been tested and this proportion is even lower in rural populations.[76] Furthermore, only 0.5% of pregnant women attending urban health facilities are counselled, tested or receive their test results.[76] Again, this proportion is even lower in rural health facilities.[76] Since donors may therefore be unaware of their infection, donor blood and blood products used in medicine and medical research are routinely screened for HIV.[77]

HIV-1 testing consists of initial screening with an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to HIV-1. Specimens with a nonreactive result from the initial ELISA are considered HIV-negative unless new exposure to an infected partner or partner of unknown HIV status has occurred. Specimens with a reactive ELISA result are retested in duplicate.[78] If the result of either duplicate test is reactive, the specimen is reported as repeatedly reactive and undergoes confirmatory testing with a more specific supplemental test (e.g., Western blot or, less commonly, an immunofluorescence assay (IFA)). Only specimens that are repeatedly reactive by ELISA and positive by IFA or reactive by Western blot are considered HIV-positive and indicative of HIV infection. Specimens that are repeatedly ELISA-reactive occasionally provide an indeterminate Western blot result, which may be either an incomplete antibody response to HIV in an infected person, or nonspecific reactions in an uninfected person.[79] Although IFA can be used to confirm infection in these ambiguous cases, this assay is not widely used. Generally, a second specimen should be collected more than a month later and retested for persons with indeterminate Western blot results. Although much less commonly available, nucleic acid testing (e.g., viral RNA or proviral DNA amplification method) can also help diagnosis in certain situations.[78] In addition, a few tested specimens might provide inconclusive results because of a low quantity specimen. In these situations, a second specimen is collected and tested for HIV infection.

Treatment See also AIDS Treatment.

Abacavir - a nucleoside analog reverse transcriptase inhibitors (NARTIs or NRTIs) The chemical structure of AbacavirThere is currently no vaccine or cure for HIV or AIDS. The only known method of prevention is avoiding exposure to the virus. However, an antiretroviral treatment, known as post-exposure prophylaxis is believed to reduce the risk of infection if begun directly after exposure.[80] Current treatment for HIV infection consists of highly active antiretroviral therapy, or HAART.[81] This has been highly beneficial to many HIV-infected individuals since its introduction in 1996, when the protease inhibitor-based HAART initially became available.[82] Current HAART options are combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of anti-retroviral agents. Typically, these classes are two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Because AIDS progression in children is more rapid and less predictable than in adults, particularly in young infants, more aggressive treatment is recommended for children than adults.[83] In developed countries where HAART is available, doctors assess their patients thoroughly: measuring the viral load, how fast CD4 declines, and patient readiness. They then decide when to recommend starting treatment.[84]

HAART allows the stabilisation of the patient’s symptoms and viremia, but it neither cures the patient, nor alleviates the symptoms, and high levels of HIV-1, often HAART resistant, return once treatment is stopped.[85][86] Moreover, it would take more than a lifetime for HIV infection to be cleared using HAART.[87] Despite this, many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to a large reduction in HIV-associated morbidity and mortality in the developed world.[82][88][89] A computer based study in 2006 projected that following the 2004 United States treatment guidelines gave an average life expectancy of an HIV infected individual to be 32.1 years from the time of infection if treatment was started when the CD4 count was 350/µL.[90] This study was limited as it did not take into account possible future treatments and the projection has not been confirmed within a clinical cohort setting. In the absence of HAART, progression from HIV infection to AIDS has been observed to occur at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2 months.[91] However, HAART sometimes achieves far less than optimal results, in some circumstances being effective in less than fifty percent of patients. This is due to a variety of reasons such as medication intolerance/side effects, prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV. However, non-adherence and non-persistence with antiretroviral therapy is the major reason most individuals fail to benefit from HAART.[92] The reasons for non-adherence and non-persistence with HAART are varied and overlapping. Major psychosocial issues, such as poor access to medical care, inadequate social supports, psychiatric disease and drug abuse contribute to non-adherence. The complexity of these HAART regimens, whether due to pill number, dosing frequency, meal restrictions or other issues along with side effects that create intentional non-adherence also contribute to this problem.[93][94][95] The side effects include lipodystrophy, dyslipidaemia, insulin resistance, an increase in cardiovascular risks and birth defects.[96][97]

The timing for starting HIV treatment is still debated. There is no question that treatment should be started before the patient's CD4 count falls below 200, and most national guidelines say to start treatment once the CD4 count falls below 350; but there is some evidence from cohort studies that treatment should be started before the CD4 count falls below 350.[98][88] There is also evidence to say that treatment should be started before CD4 percentage falls below 15%.[99] In those countries where CD4 counts are not available, patients with WHO stage III or IV disease[100] should be offered treatment.

Italic text 13 Notes and references 14 External links