What is human immunodeficiency virus (HIV)?

Causes and Symptoms

Human immunodeficiency virus, or HIV, is a human retrovirus containing two copies of a 9,749-base ribonucleic acid (RNA)
molecule as its genetic material. Among the proteins carried by retrovirus particles is an enzyme called reverse transcriptase, which upon infection of the cell transcribes the RNA genome into a DNA copy. The DNA copy then integrates into a human chromosome and is maintained in a form called a provirus. The provirus acts as a template to produce copies of the HIV RNA genome. Once the provirus has integrated, infection is irreversible.

HIV falls into the subgroup of retroviruses called lentiviruses, “slow viruses” that do not cause a disease state until many years after infection. The period of time between HIV infection and development of disease averages between five and ten years in untreated persons. Despite the absence of symptoms, the person may be infectious during this period.

There are two forms of HIV. HIV-1, which arose in central Africa, is the predominant form throughout most of the world, including the United States; HIV-2, a less common form found in western Africa, is less harmful and reproduces more slowly. These viruses evolved from related agents called simian immunodeficiency viruses (SIV) in apes and monkeys. HIV-1 is believed to have arisen from SIV found in chimpanzees in either the Republic of the Congo or Cameroon, while HIV-2 is believed to have arisen from SIV of the sooty mangabey monkey of western Africa.

HIV is transmitted only through the exchange of body fluids, including semen, vaginal fluid, blood, and human milk. Therefore, the primary routes are sexual transmission, the use of dirty needles by intravenous drug users, and HIV-positive mother-to-child transmission during childbirth or from HIV-contaminated breast milk. Transmission may also occur through dirty needles used in body piercing or tattooing. Early in the AIDS epidemic, infection was also acquired through the transfusion of contaminated blood or blood products, leading to a very high rate of transmission to hemophiliacs. Today, such transmission is extremely rare, as the blood supply is routinely tested for HIV.

Treatment and Therapy

The lack of fidelity associated with replication of HIV results in a high number of mutations, making it difficult for the immune system of the infected host to respond as it would to infections by other viruses. Consequently, no effective vaccine to prevent infection with HIV has been developed.

The US Food and Drug Administration (FDA) has approved some two dozen drugs to treat HIV infection; more are in clinical trials. These drugs fall into four categories: nucleoside or nucleotide analogues, which act as direct inhibitors of reverse transcriptase; inhibitors that indirectly inhibit reverse transcriptase by binding to the enzyme; protease inhibitors that interfere with the processing of HIV proteins and assembly of progeny viruses; and inhibitors of entry of HIV into the cell. Because the virus has a very high rate of mutation, resistance to individual anti-HIV drugs may appear quickly. Present therapy, called highly active antiretroviral therapy (HAART), involves the use of three or four anti-HIV drugs simultaneously. HAART therapy, also termed “cocktail therapy,” increases efficacy and reduces the probability of developing simultaneous resistance to all three or four drugs being used.

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