HIV is the human immunodeficiency virus that causes AIDS—acquired immune deficiency syndrome. HIV is a sexually transmitted infection (STI) that can be contracted from infected body fluids including semen, blood, and breast milk. The virus destroys immune-system cells—especially T-cells—that carry the CD4 protein on their surfaces. The weakened immune system leaves people vulnerable to increasingly severe opportunistic infections (OIs) and certain cancers. An OI or cancer or a T-cell count below 200 per mL of blood marks the transition from HIV infection to AIDS. By the late twentieth century, HIV/AIDS had become a worldwide pandemic. The unique response to HIV/AIDS was spearheaded by people with AIDS and their advocates.
As of 2017, an estimated 37 million people worldwide were living with HIV, but only about 60% were aware of their infection, and only about half had access to lifesaving antiretrovirals (ARVs). Although there were an estimated 2.1 million new infections in 2015, this represented a 35% decrease in new infections since 2000. Similarly, although there were an estimated 1.8 million children under 15 living with HIV in 2016—most infected perinatally (during birth)—new infections in children had declined 51% since 2010, and perinatal infection had been nearly eliminated in the United States. At the other extreme, there are an increasing number of older Americans living with HIV/AIDS. Worldwide, slightly more women than men are infected. About 19% of new 2015 infections were in women aged 15–24.
Approximately 95% of cases of HIV/AIDS are in Africa and Southeast Asia. Sub-Saharan Africa is most affected, with an estimated 25.6 million—at least 5% of all adults—living with HIV and two-thirds of all new infections. Whereas 95% of HIV-infected pregnant South African women receive antiretrovirals to prevent mother-to-child transmission (MTCT), only about 30% of HIV-infected pregnant Nigerian women receive antiretrovirals.
In the United States, an estimated 1.2 million people were living with HIV at the end of 2013, with about 13% unaware of their infection. There were 39,513 new HIV diagnoses in 2015—a decline of 9% since 2010, with the biggest drop among gay and bisexual Caucasian men. New 2015 diagnoses were:
HIV is a retrovirus with RNA as its genetic material. HIV-1 is responsible for the global pandemic. HIV-2 is uncommon outside of West Africa, appears to be less easily transmitted, and has a longer latency between infection and AIDS.
It is believed that HIV evolved from the simian immunodeficiency virus contracted from chimpanzee bush meat in the Central African rainforest around the turn of the twentieth century. As the virus moved among humans, first in rural Africa and then in cities, it mutated repeatedly, becoming increasingly diverse. The earliest identified HIV came from a blood sample collected in Kinshasa, Congo, in 1959. The virus reached Haiti in the 1960s and the United States by at least the 1970s.
In 1981, deadly outbreaks of very rare diseases began appearing among gay men in New York City and San Francisco: PCP—pneumonia caused by the yeast-like fungus Pneumocystis jirovecii (formerly P. carinii)—as well as Kaposi sarcoma (KS), gastrointestinal parasites, and lymphadenopathy (swollen, knobby lymph glands). The Centers for Disease Control and Prevention (CDC) later estimated that by 1981 there were already 42,000 Americans—primarily gay men and Haitian immigrants—living with HIV and 20,000 new infections annually. By 1982—when the term “AIDS“was introduced—an estimated 43% of San Francisco's gay male population and 26% of New York's were infected. Similar outbreaks in Africa and the Caribbean affected heterosexual men and women, newborns, injected-drug users, and people with hemophilia. Furthermore, Africans had been dying for years from a mysterious wasting syndrome.
In 1983, French and American scientists identified HIV as the cause of AIDS, but conflicts over priority and patents significantly slowed research and treatments. During the 1980s, 100,000 men died of AIDS in New York City alone. By 1992, it was the number one cause of death among U.S. men aged 25–44.
Most people with untreated HIV infections eventually develop AIDS, usually over several years, although the disease typically progresses faster in children and the elderly. AIDS-related deaths peaked in 2005 at 2.3 million worldwide and have since fallen significantly. With the introduction of protease inhibitors and combination antiretroviral therapy in the mid-1990s, U.S. AIDS deaths immediately declined by 47%. As of 2016, more than 18 million people worldwide were receiving treatment, for a global coverage of about 46%, including more than 70% of pregnant women. However as of 2017, there were still about 2 million deaths annually from lack of access to antiretrovirals, and AIDS remained a leading cause of childhood death in many parts of Africa and Southeast Asia. Almost all deaths are from one of the 24 known deadly OIs, with PCP the leading cause, followed by KS, lymphoma, toxoplasmosis, and wasting caused by Mycobacterium avium-intracellulare. HIV also directly affects the brain, causing AIDS dementia complex (ADC).
At a national conference of gay and lesbian healthcare workers in 1983, activists formulated the “Denver Principles,” demanding basic rights for people with AIDS and their involvement at all levels of healthcare decision-making. This signaled the beginnings of a patient-advocacy movement that would revolutionize the global health response. Under activist pressure, the drug company Burroughs Wellcome resurrected an old cancer drug called azidothymidine (AZT). Early clinical-trial results were so spectacular that the trial's placebo arm was abruptly halted as inhuman. In the fastest-ever drug approval by the Food and Drug Administration (FDA), AZT became the first nucleoside analog reverse transcriptase inhibitor (NRTI)—and Burroughs Wellcome raised the price to $10,000 a year, making it the most expensive drug in history. Although HIV quickly became AZT-resistant, and the drug was too toxic for many people with AIDS, with no new treatments in the pipeline, a new group, the AIDS Coalition to Unleash Power (ACT UP), launched a multipronged attack. Under the ubiquitous banner SILENCE=DEATH, ACT UP grew to include 148 chapters in 19 countries, leading demonstrations, sitins, and other actions targeting the National Institutes of Health (NIH), FDA, and drug companies. Activists became their own healthcare providers, researchers, drug smugglers, pharmacists, and lobbyists, with their own publications, libraries, and laboratories. ACT UP's Treatment + Data Committee eventually won the respect and cooperation of the scientific establishment and began partnering with leading researchers and the FDA. Meanwhile, AIDS doctors—horrified that slow-paced clinical trials were treating dying people with AIDS with placebos and denying them prophylaxis for PCP and other OIs—set up independent community-based drug trials. In 1989, the FDA finally approved aerosol pentamidine as PCP prophylaxis—the first drug ever released based on data from community researchers. With its approval of DHPG for AIDS-related blindness, the FDA, for the first time, reversed its position on a drug in response to patient pressure and without formal trials. As ACT UP imposed on AIDS research at the NIH, it demanded the inclusion of women, children, people of color, and intravenous drug users in clinical trials.
HIV/AIDS finally came to the attention of the U.S. Congress and broader public with revelations that the popular actor Rock Hudson and a 13-year-old with hemophilia were dying of AIDS. The Surgeon General called for a nationwide educational campaign—including early school-based sex education, condom use, and voluntary testing—and every U.S. household received an informational brochure. Eventually, the CDC took control of the response, including:
The World Health Organization (WHO) tracks HIV/AIDS. The 69th World Health Assembly's strategies for 2016–2021 include information, intervention, equal global coverage, sustainable financing, and innovation. WHO recommendations include:
Other international programs include:
HIV is transmitted through contact with infected body fluids and mucus membranes. Unprotected sexual activity, especially anal intercourse, with an HIV-infected partner poses the greatest risk. STIs such as syphilis and gonorrhea significantly increase the risk of both transmitting and contracting HIV. In Africa, HIV is spread primarily through heterosexual activity. Schistosomiasis—a parasitic disease that affects up to 50% of women in some parts of Africa—can damage vaginal tissues, increasing susceptibility to HIV. Although 10% of U.S. diagnoses are in intravenous drug users, needle exchanges have reduced new infections in this population by half. Beginning in the mid-1980s, screening eliminated the blood supply as a source of HIV in the developed world. Safety precautions made healthcare-associated transmission extremely rare. Unfortunately, the perception that HIV/AIDS is now preventable or treatable has led to an increase in high-risk sexual behaviors. Furthermore, older adults are five times more likely than younger people to have unprotected sex, and older women are at greater risk for infection due to thinning of the vaginal wall. Nevertheless, combination antiretroviral therapy (cART) reduces HIV transmission by almost 96%.
HIV fuses with human cells by attaching to the CD4 protein receptor on the surface of white blood cells. HIV requires a co-receptor called CCR5, which is present on immune-system cells in mucous membranes of the genitalia and gastrointestinal tract, although about 1% of people of Northern European ancestry have two copies of a CCR5 mutation that protects against HIV infection. HIV inserts its RNA into cells, reverse transcribes its RNA into DNA, and, within less than two days, produces new viral particles that burst the cells to release more virus. Eventually, so many white blood cells are destroyed that the weakened immune system cannot fight off OIs or cancers. The virus also can remain silent (latent) within human DNA to be activated later.
Untreated HIV/AIDS generally progresses through three stages. Early-stage infection often causes no symptoms; however, within a month about 30% of people develop acute retroviral syndrome (ARS), a flulike illness with fever, headache, swollen lymph nodes, and fatigue. Although symptoms disappear within a few weeks, people remain highly contagious.
The second stage—clinical latency or asymptomatic, chronic infection—lasts a decade or more, with the virus reproducing at very low—but transmissible—levels. Symptoms, if present, can include:
As the viral load—the number of viral particles in the blood—increases toward the end of stage 2, CD4 levels fall below 200. Symptoms and infectiousness increase. Full-blown AIDS is characterized by OIs and/or AIDS-related cancers:
AIDS progresses faster in children, with delayed growth, fevers, recurrent ear infections, and other frequent illnesses. Children are more susceptible to bacterial infections, lung inflammation, and AIDS-related brain disorders.
An OI and/or unsafe sexual practices or intravenous drug use may suggest HIV/AIDS. The initial physical exam may include neurologic and mentalstatus examinations, since ADC may be the first symptom in advanced cases.
NATs measure viral load.
HIV/AIDS progression is indicated by:
Genotypic or phenotypic tests are used to choose antiretrovirals. Genotypic testing identifies mutations in HIV RNA associated with specific antiretroviral resistance. Phenotypic testing directly measures the sensitivity of an HIV strain to particular drugs and drug combinations.
AIDS-related infections and complications may require tests for:
Procedures used to diagnose OIs and complications include:
Combination antiretroviral therapy can mean taking multiple drugs or combination pills at specific times every day for life. At least three drugs from two of the six different classes are combined to avoid creating strains resistant to a single drug.
Other common medications include:
HIV-positive pregnant women usually take zidovudine (ZDV) beginning at 14 weeks of gestation. It is administered intravenously during labor and delivery. Newborns are given liquid ZDV for six weeks and possibly additional antiretrovirals, as well as PCP prophylaxis, since PCP is a major cause of death during the first year.
Good nutrition, weight maintenance, and regular physical exercise—particularly weight-training—are important for people with AIDS. Food safety is a major concern. Complementary and alternative measures—including multivitamins, acupuncture, yoga, massage therapy, and relaxation techniques—may reduce symptoms, counteract drug effects, improve mood, and relieve depression. Whey protein may help with weight gain and reducing diarrhea. St. John's wort and garlic supplements can interact with some antiretrovirals, reducing their effectiveness by at least 50%.
Only once has HIV/AIDS appeared to be cured. In Germany in 2007, an American man with AIDS and leukemia received bone-marrow transplants from a donor lacking CCR5. As of 2017, he remained HIV-free without combination antiretroviral therapy. Others thought to be HIV-free after similar transplants suffered severe resurgences when combination antiretroviral therapy was discontinued.
HIV-positive pregnant women on combination antiretroviral therapy have only a 1%–2% risk of MTCT. With a viral load below 1,000 and ZDV, the risk is almost zero. Cesarean delivery before onset of labor and membrane rupture reduces the risk of transmission with high viral loads. Although HIV-infected infants have no symptoms at birth, about 15% develop serious symptoms or die within the first year. Almost half die by age ten. However, combination antiretroviral therapy can significantly reduce the risk of death.
Because HIV mutates so rapidly, the development of both preventive and therapeutic vaccines has proved exceedingly difficult. However PrEP—a combination of tenofovir and emtricitabine called Truvada—reduces the risk of contracting HIV from sexual activity by more than 90% if taken consistently on a daily basis. The risk is even lower if combined with the condom use and other preventive measures. PrEP reduces the risk from injecting drugs by more than 70%. PEP initiated within 72 hours of exposure and taken once or twice daily for 28 days often prevents infection but is not 100% effective. Daily combination antiretroviral therapy initiated soon enough after HIV infection can prevent progression to AIDS and reduce the risk of transmission by up to 96%. ART for HIV-positive pregnant women—along with Cesarean delivery and avoidance of breastfeeding—reduce MTCT to less than 1%.
The CDC recommends HIV screening at least once for everyone aged 13–64 and annual screening for those at risk—including anyone with hepatitis B or C, TB, or an STI; who had a blood transfusion prior to 1985; or who could have otherwise been exposed. Gay or bisexual men may require testing as often as every three–six months. The American Academy of Pediatrics recommends testing for all sexually active youth and 16–18-year-olds in high-risk areas. HIV testing is included in standard prenatal care for all pregnant women, with repeat testing during the third trimester for women at high risk.
The risk of contracting HIV can be lowered by safe sexual practices and other precautions. People living with HIV must avoid behaviors that can spread infection to sexual or needle-sharing partners.
See also Epidemiology ; Globalization and emerging diseases ; Tuberculosis .
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Margaret Alic, PhD