HIV/AIDS

• 1. Introduction

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  On the 5th of June 1981, the U.S. Centers for Disease Control and Prevention reported five cases in the United States. The men shared a rare lung infection, Pneumocystis carinii pneumonia, normally seen only in people with badly damaged immune systems. None of them had an obvious reason for that damage. Days earlier, on the 18th of May, a gay newspaper in New York had run the first news story on the disease. Soon a strange skin cancer called Kaposi's sarcoma began appearing in young men too. Clinicians were watching a new syndrome take shape before anyone could name it. The virus behind it, the human immunodeficiency virus, attacks the immune system itself. Without treatment it can progress to acquired immunodeficiency syndrome, or AIDS. Why did a microbe that hides inside the body's own defenders go unrecognized for so long? How did a virus from primates in west-central Africa reach a single individual, then the world? And how did a near-certain death sentence become a manageable chronic condition that lets a person die with the virus, not of it? Between the first recognition of AIDS and 2024, the disease is estimated to have caused at least 42.3 million deaths worldwide.

• 2. Inside The Immune System

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  CD4 positive T cells sit at the center of the body's defenses, and HIV hunts them down. The virus is a retrovirus of the genus Lentivirus, within the family Retroviridae, and it also infects macrophages and dendritic cells. It carries its genome as single-stranded, positive-sense, enveloped RNA. Once inside a target cell, a viral enzyme called reverse transcriptase copies that RNA into double-stranded DNA. A second enzyme, integrase, then splices the viral DNA into the cell's own genome. Once integrated, the virus can fall silent and latent, hiding from immune detection, or switch on and churn out new particles. HIV spreads between CD4 cells along two routes at once. In cell-free spread, particles bud off, drift into the blood, and infect another cell by chance. In cell-to-cell spread, the virus passes directly from one cell to its neighbor. This hybrid strategy helps it keep replicating against antiretroviral drugs. Much of the damage comes early, in the first weeks. The bulk of CD4 cell loss happens in the intestinal mucosa, which holds most of the body's lymphocytes. Those mucosal cells carry the CCR5 protein, the co-receptor HIV uses to enter, while only a small fraction of CD4 cells in the bloodstream do. A genetic change that alters CCR5 on both chromosomes can block HIV-1 infection almost completely. That single quirk of the CCR5 protein would later shape some of the rare cases of people cleared of the virus entirely.

• 3. Three Stages Of An Infection

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  Two to four weeks after exposure, many people develop an illness that looks like influenza, mononucleosis or glandular fever. This is acute HIV, the first of three stages. Symptoms appear in 40 to 90 percent of cases, with fever, tender swollen lymph nodes, throat inflammation, a rash, headache, tiredness, and sores in the mouth or genitals. A maculopapular rash on the trunk shows up in 20 to 50 percent of cases. The signs are rarely recognized, and doctors often mistake them for ordinary infections. Then comes clinical latency, a quiet stretch that can run from about three years to over twenty, averaging roughly eight. Most people feel few symptoms early on, though many later develop fever, weight loss, gut problems and muscle pain. A minority defy the pattern. About 5 percent hold high CD4 counts for more than five years without treatment, known as HIV controllers or long-term nonprogressors. Roughly 1 in 300 keep the virus undetectable on their own, the elite controllers. The third stage is AIDS, defined by a CD4 count below 0.2 cells per millilitre or by specific associated diseases. Around half of untreated people reach it within ten years. The conditions that announce it include pneumocystis pneumonia in 40 percent of cases, HIV wasting syndrome in 20 percent, and esophageal candidiasis. Kaposi's sarcoma, the most common cancer, strikes 10 to 20 percent of people with HIV, and diarrhea afflicts about 90 percent of those with AIDS.

• 4. How It Spreads

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  Blood transfusion with infected blood transmits HIV in about 90 percent of cases, the highest per-act risk of any route. The virus moves by three main paths: sexual contact, exposure to infected blood or tissues, and from mother to child during pregnancy, delivery or breastfeeding. Saliva, sweat, tears and urine do not carry it unless contaminated with blood, and mosquitoes cannot transmit it. Sexual contact is the most frequent mode worldwide, most often between people of opposite sex, though patterns vary by country. Anal intercourse carries an especially high risk, estimated at 1.4 to 1.7 percent per act. Genital ulcers raise the chance of transmission roughly fivefold, and a person's viral load matters enormously. During the first 2.5 months of infection, when viral load is high, infectiousness runs twelve times higher. Sharing a needle during drug injection carries a risk between 0.63 and 2.4 percent per act. A needle-stick injury from an infected person runs about 0.3 percent, roughly 1 in 333. In wealthy countries, screening has made transfusion risk vanishingly small, reported at one in five million in the UK in 2011. In low-income areas, up to 15 percent of infections may come from infected blood products. One fact reshaped the conversation entirely. A person on long-term treatment whose viral load is undetectable has effectively no risk of transmitting HIV sexually. First publicized controversially in the 2008 Swiss Statement, it is now accepted as medically sound and spread by UNAIDS as Undetectable equals Untransmittable.

• 5. From Death Sentence To Chronic Illness

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  Highly active antiretroviral therapy slows the disease and turns it chronic, though no cure exists. Treatment combines at least three drugs from at least two of the eight classes of antiretroviral agents, of which there are over 30. A standard start pairs two nucleoside reverse transcriptase inhibitors with a third drug. The World Health Organization and the United States recommend starting as soon as diagnosis is made, regardless of CD4 count, and continuing without breaks. The goal is a plasma HIV-RNA count below 50 copies per millilitre, and on these terms treatment succeeds in more than 95 percent of people in the first year. The payoff is steep. Antiretroviral therapy and good prevention of opportunistic infections cut the death rate by 80 percent. They raise life expectancy for a newly diagnosed young adult to 20 to 50 years, between two thirds and nearly that of the general population. Treatment also cuts the risk of acquiring tuberculosis by 70 percent. New formulations are easing the daily burden. The European Medicines Agency backed rilpivirine and cabotegravir as the first long-acting injectables, given monthly or every two months instead of daily pills. Prevention now reaches beyond the infected. Consistent condom use lowers transmission risk by about 80 percent. Pre-exposure prophylaxis, or PrEP, with tenofovir protects high-risk groups, and post-exposure prophylaxis within 48 to 72 hours can stop infection after a needle stick or assault. In 2015, Cuba became the first country to eradicate mother-to-child transmission.

• 6. Two Labs And A Disputed Name

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  In 1983, two research groups published in the same issue of the journal Science, each claiming a novel retrovirus tied to AIDS. Robert Gallo's group reported a virus resembling other human T-lymphotropic viruses they had isolated, and called it HTLV-III. Luc Montagnier's group isolated a virus from a patient with swollen neck lymph nodes and physical weakness. Montagnier showed its core proteins differed immunologically from HTLV-I, and named it lymphadenopathy-associated virus, or LAV. The two viruses turned out to be the same. In 1986, LAV and HTLV-III were renamed HIV. Naming the syndrome had been just as fraught. Early on the CDC had no official name, sometimes calling it the 4H disease because it seemed to affect heroin users, homosexuals, hemophiliacs and Haitians. The label GRID, for gay-related immune deficiency, also circulated. After it became clear the disease was not confined to gay men, the term AIDS was introduced at a meeting in July 1982, and by September the CDC adopted it. Two distinct viruses were eventually characterized. HIV-1, the one first discovered, is more virulent and infective and causes most infections globally. HIV-2 transmits more poorly and stays largely confined to West Africa.

• 7. Tracing The Origin

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  Around 1910, the most recent common ancestor of the HIV-1 M group existed, according to genetic studies of the virus. Both HIV-1 and HIV-2 came from non-human primates in west-central Africa and crossed to humans in the early 20th century. HIV-1 appears to have arisen in southern Cameroon from SIVcpz, a simian immunodeficiency virus of the chimpanzee subspecies Pan troglodytes troglodytes. The closest relative of HIV-2 is SIVsmm, from the sooty mangabey of coastal West Africa. Crossing the species barrier was not enough on its own. SIV is a weak virus, usually suppressed by the human immune system within weeks, so several quick transmissions were needed for it to mutate into HIV. That required high-risk channels thought absent in Africa before the 20th century. One view links the epidemic to colonialism and the growth of large colonial cities, with rising prostitution and genital ulcer diseases. As of 1928, as many as 45 percent of female residents of eastern Kinshasa were thought to be prostitutes, and by 1933 around 15 percent of the city had syphilis. The trail then reaches across the Atlantic. The earliest well-documented human case dates to 1959 in the Congo. Dr. Jacques Pepin, author of The Origins of AIDS, argues a Haitian may have carried the virus to the United States around 1969. By 1978, HIV-1 prevalence among gay men in New York City and San Francisco was estimated at 5 percent.

• 8. Fear, Faith And Famous Faces

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  On the 2nd of October 1985, the American actor Rock Hudson died, months after announcing on the 25th of July that he had the virus. His was one of the first high-profile cases, and it put a familiar face on a disease shrouded in fear. The tennis player Arthur Ashe, diagnosed HIV-positive on the 31st of August 1988 after blood transfusions during heart surgery, kept his condition private until April 1992 and died on the 6th of February 1993, aged 49. The British rock star Freddie Mercury revealed his diagnosis only a day before he died, on the 24th of November 1991. Stigma shadowed every story. It took the form of ostracism, rejection, forced testing without consent, and even violence, and fear of that violence kept people from testing or seeking care. The NAMES Project AIDS Memorial Quilt, conceived in 1985, honored those who had died when stigma denied many of them funerals. Misconceptions deepened the harm. In 2014, parts of the British public wrongly believed HIV could spread by kissing, sharing a glass, or a toilet seat. Some religious authorities opposed condoms, and in 2011 it was reported that several Londoners stopped their medication on a pastor's advice, leading to deaths. The damage could also be governmental. South Africa's official embrace of AIDS denialism from 1999 to 2005 crippled its response, and the NIH and the Gates Foundation have since pledged $200 million toward a global cure.