HIV

Human immunodeficiency virus, commonly known by the initialism HIV, is a retrovirus that primarily infects vital components of the human immune system such as CD4+ T cells, macrophages and dendritic cells. It also directly and indirectly destroys CD4+ T cells. As CD4+ T cells are required for the proper functioning of the immune system, when enough CD4+ T cells have been destroyed by HIV, the immune system functions poorly, leading to the syndrome known as AIDS. HIV also directly attacks organs, such as the kidneys, the heart and the brain leading to acute renal failure, cardiomyopathy, dementia and encephalopathy. Many of the problems faced by people infected with HIV result from failure of the immune system to protect from opportunistic infections and cancers.

HIV is transmitted through direct contact of a mucous membrane with a bodily fluid containing the HIV virus (such as blood, semen, vaginal fluid, preseminal fluid (fluid ejected by the penis before ejaculation) or breast milk). This transmission can come in the form of: penetrative (anal or vaginal) sex; oral sex; blood transfusion; contaminated needles; exchange between mother and infant during pregnancy, childbirth, or breastfeeding; or other exposure to one of the above bodily fluids.

AIDS is thought to have originated in sub-Saharan Africa during the twentieth century and it is now a pandemic. At the end of 2004, UNAIDS estimated that nearly 40 million people were currently living with HIV. The World Health Organization estimated that the AIDS epidemic had claimed more than 3 million people and that 5 million people had acquired HIV in the same year. Currently it is estimated that 28 million people have died and that it is set to infect 90 million people in Africa, resulting in a minimum estimate of 18 million orphans in Africa alone.

Introduction
In 1983, scientists led by Luc Montagnier at the Pasteur Institute in France first discovered the virus that causes AIDS (Barré-Sinoussi et al., 1983). They called it lymphadenopathy-associated virus (LAV). A year later a team led by Robert Gallo of the United States confirmed the discovery of the virus, but they renamed it human T lymphotropic virus type III (HTLV-III) (Popovic et al., 1984). The dual discovery led to considerable scientific fall-out, and it was not until President Mitterand of France and President Reagan of the USA met that the major issues were ironed out. In 1986, both the French and the US names were dropped in favour of the new term human immunodeficiency virus (HIV) (Coffin, 1986).

HIV is a member of the genus lentivirus (ICTVdb, 61.0.6), part of the family of retroviridae (ICTVdb, 61). Lentiviruses have many common morphologies and biological properties. Many species are infected by lentiviruses, which are characteristically responsible for long duration illnesses associated with a long period of incubation (Lévy, 1993). Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon infection of the target-cell, the viral RNA genome is converted to double-stranded DNA by a virally encoded reverse transcriptase which is present in the virus particle. This viral DNA is then integrated into the cellular DNA for replication using cellular machinery. Once the virus enters the cell, two pathways are possible: either the virus becomes latent and the infected cell continues to function or the virus becomes active, replicates and a large number of virus particles are liberated which can infect other cells.

Two species of HIV infect humans: HIV-1 and HIV-2. HIV-1 is the more virulent and easily transmitted, and is the source of the majority of HIV infections throughout the world; HIV-2 is largely confined to west Africa (Reeves and Doms, 2002). Both species originated in west and central Africa, jumping from primates to humans in a process known as zoonosis. HIV-1 has evolved from a simian immunodeficiency virus (SIVcpz) found in the chimpanzee subspecies, Pan troglodytes troglodytes (Gao et al., 1999). HIV-2 crossed species from a different strain of SIV, found in sooty mangabey monkeys in Guinea-Bissau (Reeves and Doms, 2002). It is possible that that HIV-1 entered the human populations in the 1930's.

Transmission
Since the beginning of the epidemic, three main transmission routes of HIV have been identified:

Sexual route. The majority of HIV infections are acquired through unprotected sexual relations. Sexual transmission occurs when there is contact between sexual secretions of one partner with the rectal, genital or mouth mucous membranes of another. According to the French ministry for health, the probability of transmission per act varies from 0.03% to 0.07% for the case of receptive vaginal sex, from 0.02 to 0.05% in the case of insertive vaginal sex, from 0.01% to 0.185% in the case of insertive anal sex, and 0.5% to 3% in the case of receptive anal sex [1].
Blood or blood product route. This transmission route is particularly important for intravenous drug users, hemophiliacs and recipients of blood transfusions and blood products. It is also of concern for persons receiving medical care in regions where there is prevalent substandard hygiene in the use of injection equipment (e.g. reused needles in Third World settings). Health care workers (nurses, laboratory workers, doctors, etc) are also directly concerned, although more rarely. Also concerned by this route are people who give and receive tattoos, piercings and scarification procedures.
Mother-to-child route. The transmission of the virus from the mother to the child can occur in utero during the last weeks of pregnancy and at childbirth. Breast feeding also presents a risk of infection for the baby. In the absence of treatment, the transmission rate between the mother and child was 20%. However, where treatment is available, combined with the availability of Cesarian section, this has been reduced to 1%.
HIV has been found at low concentrations in the saliva, tears and urine of infected individuals, but the risk of transmission by these secretions is considered to be negligible.

The use of physical barriers such as the latex condom is widely advocated to reduce the sexual transmission of HIV. Recently, it has been proposed that male circumcision may reduce the risk of HIV transmission (Siegfried et al., 2005), but many experts believe that it is premature to recommend male circumcision as part of HIV prevention programs (WHO, 2005).

For more details on this topic, see AIDS prevention

The clinical course of HIV-1 infection
 
Figure 1. Graph showing HIV virus and CD4+ levels over the course of an untreated infectionInfection with HIV-1 is associated with a progressive loss of CD4+ T-cells. This rate of loss can be measured and is used to determine the stage of infection. The loss of CD4+ T-cells is linked with an increase in viral load. The clinical course of HIV-infection generally includes three stages: primary infection, clinical latency and AIDS (Figure 1). HIV plasma levels during all stages of infection range from just 50 to 11 million virions per ml (Piatak et al., 1993).

Primary Infection
Primary, or acute infection is a period of rapid viral replication that immediately follows the individual's exposure to HIV. During primary HIV infection, most individuals (80 to 90 %) develop an acute syndrome characterised by flu-like symptoms of fever, malaise, lymphadenopathy, pharyngitis, headache, myalgia, and sometimes a rash (Kahn and Walker, 1998). Within an average of three weeks after transmission of HIV-1, a broad HIV-1 specific immune response occurs that includes seroconversion. 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. Since not all patients develop it, and since the same symptoms can be caused by many other common diseases, it cannot be used as an indicator of HIV infection. However, recognizing the syndrome is important because the patient is much more infectious during this period

Clinical Latency
As a result of the strong immune defense, the number of viral particles in the blood stream declines and the patient enters clinical latency (Figure 1). Clinical latency is variable in length and can vary between two weeks and 20 years. During this phase HIV is active within lymphoid organs where large amounts of virus become trapped in the follicular dendritic cells (FDC) network early in HIV infection. The surrounding tissues that are rich in CD4+ T-cells also become infected, and viral particles accumulate both in infected cells and as free virus. Individuals who have entered into this phase are still infectious.

The declaration of AIDS
AIDS is the most severe manifestation of infection with HIV. Acute HIV infection progresses over time to clinical latent HIV infection and then to early symptomatic HIV infection and later, to AIDS, which is identified on the basis of certain infections.

For more details on this topic, see AIDS symptoms.

Treatment
HIV infection is a chronic infectious disease that can be treated, but not yet cured. There are effective means of preventing complications and delaying, but not preventing, progression to AIDS. At the present time, not all persons infected with HIV have progressed to AIDS, but it is generally believed that the majority will. People with HIV infection need to receive education about the disease and treatment so that they can be active partners in decision making with their health care provider.

A combination of several antiretroviral agents, termed Highly Active Anti-Retroviral Therapy HAART, has been highly effective in reducing the number of HIV particles in the blood stream (as measured by a blood test called the viral load). This can improve T-cell counts. This is not a cure for HIV, and people on HAART with suppressed levels of HIV can still transmit the virus to others through sex or sharing of needles. There is good evidence that if the levels of HIV remain suppressed and the CD4 count remains greater than 200, then the quality and length of life can be significantly improved and prolonged. Improved antiretroviral inhibitors against proteins such as Reverse transcriptase, Integrase and Tat are being researched and developed. One of the most promising new therapies is a new class of drugs called fusion or entry inhibitors.

For more details on this topic, see Antiretroviral drug.
Post-exposure prophylaxis (PEP) with a course of antiviral drugs is also thought to reduce the risk of seroconversion after high risk exposure (unprotected anal or vaginal sex) to HIV. To be effective, it must be started as soon as possible after exposure and no later than 72 hours post-exposure. The treatment for HIV lasts four weeks. While there is compelling data to suggest that PEP after HIV exposure is extremely effective, there have been cases where it has failed.

As yet, no vaccine has been developed to prevent HIV infection or disease in people who are not yet infected with HIV, but the potential worldwide public health benefits of such a preventive vaccine are vast. Researchers in many countries are seeking to produce such a vaccine, including through the International AIDS Vaccine Initiative.