Human immunodeficiency virus (HIV)

ANATOMY OR SYSTEM AFFECTED: Immune system

DEFINITION: A retrovirus that attacks cells of the immune system, leading to a loss of immune function and often the development of acquired immunodeficiency syndrome (AIDS)

CAUSES: Transmission through exchange of body fluids (semen, vaginal fluid, blood, human milk)

SYMPTOMS: Flulike or mononucleosis-like symptoms upon initial transmission; later, various opportunistic infections

DURATION: Chronic, potentially fatal

TREATMENTS: Antiretroviral therapy (ART) with nucleoside or nucleotide analogues, reverse transcriptase inhibitors, protease inhibitors, and inhibitors of cellular entry; bone marrow transplant (experimental)

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 generally considered 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. An estimated 40 to 90 percent of those infected display flulike symptoms (fever, fatigue, sore throat, chills, night sweats, rash, etc.) a few weeks after infection, although some people have no symptoms.

After the acute and early infection periods is the clinical latency stage, or chronic HIV infection. Many patients have only mild symptoms or none at all during this stage, as the virus reproduces slowly. Even in the absence of symptoms, the disease can be transmitted to others. However, treatment can lower the risk of transmission and allow HIV-positive individuals to live relatively healthy lives for decades. If untreated, HIV will progress to acquired immunodeficiency syndrome (AIDS). This late stage can include symptoms such as extreme fatigue, recurrent night sweats and fever, extreme weight loss, chronic diarrhea, sores, skin blotches, neurologic disorders, pneumonia, and other concurrent diseases.

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. In the early days of 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 patients with hemophilia. 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. However, certain methods can help reduce the risk of infection. Beyond limiting one's sexual partners or abstaining from sexual activity altogether, condoms should be used correctly in every sexual encounter to help prevent HIV. Male circumcision is also believed to reduce the risk of transmission during sex. People at high risk of infection can use the daily drug emtricitabine-tenofovir (Truvada) that also reduces the chance of sexual transmission, though it is not a substitute for safe sex practices. Intravenous rug users should ensure they use only clean needles and do not share them.

The US Food and Drug Administration (FDA) has approved dozens of 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 high rate of mutation, resistance to individual anti-HIV drugs may appear quickly. Present therapy, called highly active antiretroviral therapy (HAART) or simply antiretroviral therapy (ART), involves the use of three or four anti-HIV drugs simultaneously. ART, also termed "cocktail therapy," increases efficacy and reduces the probability of developing simultaneous resistance to all three or four drugs being used. By the 2010s and 2020s, ART was effective enough to often reduce a patient's viral load to near zero, drastically reducing the risk of transmission, if taken every day as prescribed.

In 2007, the first-ever case of a patient being cured of HIV was announced. In that case, the patient was also diagnosed with leukemia, which was treated with bone marrow transplant after chemotherapy failed to have an effect. The marrow donor had a mutation of the protein CCR5 that is known to resist HIV infection. The transplant was accompanied by extremely potent immunosuppressive drugs, essentially destroying the patient's immune system before rebuilding it. The treatment led to life-threatening complications, at one point necessitating an induced coma. However, the patient recovered and was declared free of both leukemia and HIV. He lived virus-free until 2020, when he died of cancer. Doctors subsequently investigated the treatment as a potential cure for HIV.

In 2019 a second patient who underwent bone marrow transplantation was officially announced to be in long-term remission for HIV and widely considered cured of the disease. This second case was notable for using less harsh treatment but achieving similar results. Other cases were also closely watched by researchers. However, the procedure remained considered highly dangerous and experimental, especially considering the high effectiveness of modern ART; the second patient also suffered multiple infections and other side effects. Efforts continued to develop a gene therapy that could have a similar effect.

New breakthroughs in treating and curing HIV continued to emerge into the 2020s. In February 2022, a third patient was cured of HIV using a new treatment that relies on umbilical cord blood transplantation, which she was receiving to treat her leukemia. This breakthrough was significant for multiple reasons; the patient was the first woman to be cured of HIV, and since she was mixed-race, the success of her treatment provided hope for developing HIV cures that could work more effectively in people of color. Unlike the two other people who had been cured of HIV up to that point, the woman also did not develop serious side effects, such as a graft-versus-host disease, which can afflict people who receive transplants. Compared to bone marrow, umbilical cord blood also has the advantage of greater availability, as well as greater ease of finding a match between donors and recipients. In 2022, a fourth person was cured of HIV and a fifth was cured in 2023. Both had undergone stem cell transplants for cancer.

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