Date: Originating perhaps in the 1940’s or 1950’s, at pandemic levels by the 1980’s

Place: Worldwide, especially Africa

Result: Millions dead and infected

AIDS stands for acquired immunodeficiency syndrome. It is a medical syndrome caused by the HIV virus. Having HIV is not the same as having AIDS, and this is the basis for existing treatment regimens which work by preventing replication of the virus and thus preventing the infection from progressing to AIDS. The syndrome came to prominence worldwide in the 1980s. Advances in treatment have extended life expectancy today to near-normal levels for those with HIV who receive treatment. However, there are great disparities in the percentage of patients accessing treatment within the developed world and outside it, and the number of cases is still growing. In the U.S.A., there were approximately 1.2 million people living with HIV infection in 2016, while globally about 36.7 million people were living with HIV infection. Sub-Saharan Africa is the region that has been most affected and accounts for nearly 70% of persons with HIV/AIDS in the world. UNAIDS reported in 2013 that approximately 25 million people are living with HIV in Africa and 7.6 million are accessing antiretroviral medication.

Science. HIV destroys CD4 helper T lymphocytes (CD4 lymphocytes). These cells are necessary for the development and maintenance of the immune response against myriad viruses and microorganisms. According to the CDC, a person can be said to have AIDS when the number of these cells has been reduced to 200 cells/µL and when other HIV-related conditions are present.

HIV, like all viruses, is unable to proliferate on its own. The only way it can reproduce is to get its hereditary information into an appropriate host cell. The hereditary information subsequently directs the synthesis of viral proteins and new hereditary information. New viruses “self-assemble” as they bud from the cell.

A protein in the viral envelope is able to attach the virus to an appropriate host cell. The primary cellular receptor, CD4, is embedded in the membranes of macrophages and CD4 lymphocytes. After attaching the virus to CD4, the viral attachment protein binds a coreceptor, usually CCR5 on macrophages but CXCR4 on CD4 lymphocytes. Viral attachment to a coreceptor results in the subsequent fusion of the viral membrane with the host’s membrane. Upon membrane fusion, the viral core diffuses into the host’s cytoplasm, and a viral enzyme trapped inside the core converts the viral ribonucleic acid (RNA) into double-stranded deoxyribonucleic acid (DNA). The conversion of RNA into DNA is called reverse transcription and is carried out by the viral enzyme reverse transcriptase. The newly synthesized viral DNA is transported into the nucleus, where another viral enzyme called integrase modifies the DNA and promotes its integration into one of the host’s chromosomes. The integrated viral DNA, called the provirus, functions as a template for the synthesis of new viral RNA. Some of this viral RNA serves as messenger RNA (mRNA), which directs the synthesis of viral proteins. Full-length RNAs also serve as new hereditary information.

HIV is transmitted from one person to another in body fluids: blood, mothers’ milk, semen, and vaginal secretions. Although the virus can be found in saliva and tears, it is present in such low concentrations that it is almost never transmitted through these fluids. Generally, in adults, HIV is transmitted during sexual intercourse. Mucous membranes of the mouth, vagina, uterus, and colon are generally protected by macrophages that engulf viruses and degrade them. If there are too many viruses, however, some of the macrophages become infected and the virus reproduces in them.

A fetus can become infected when the virus passes through the placenta from infected mother to fetus; however, most infections in babies occur at birth because of exposure to contaminated blood or soon after birth because of drinking mother’s milk.

Once HIV infects skin or circulatory and lymphatic system macro-phages, it spreads rapidly to other macrophages in the lymph and blood. Four to six weeks after the initial infection, there may be as many as 1 million viruses per milliliter of blood produced each day. A person infected with this many viruses usually develops a headache, fever, enlarged lymph nodes, muscle aches, pharyngitis (sore throat), and a rash that may last a week or so. Some individuals experience an outbreak of oral candidiasis, caused by the yeast Candida albicans. CD4 lymphocytes sustain heavy casualties because of the high viral concentration. Typically, CD4 lymphocytes drop from about 1,000 cubic millimeters of blood to 500 cubic millimeters of blood, but in some cases the numbers may go as low as 250 cubic millimeters of blood.

About six weeks after the initial infection, the immune system begins to reduce the number of circulating viruses and the number of infected macrophages. Antibodies secreted by plasma cells into the lymph and blood link viruses together. Antibody-linked viruses are readily engulfed by macrophages and destroyed. CD8 lymphocytes, on the other hand, destroy infected macrophages. The number of circulating viruses goes from a high of about 1 million to as few as 1,000 per millileter of blood. This decline in viruses results in a partial recovery of CD4 lymphocytes. The number of CD4 lymphocytes may go from about 500 to 700 cubic millimeters of blood. The immune system is unable to eliminate all the viruses and infected macrophages. Proviruses are able to hide in Langerhans cells in the skin, glial cells and astrocytes in the brain, and dendrites in the testes and lymph nodes. Often, infected macrophages in these tissues fail to attract the attention of CD8 lymphocytes. A balance between the immune system and the proliferating virus may exist anywhere from three years to fifteen years. During this period, the infected person may show little or no signs of disease and is said to be asymptomatic. Although a person may appear to be well, they are infective because viruses are produced by some infected Langerhans cells. During the asymptomatic phase of the disease, genetically diverse populations of the virus evolve. Some populations gain the ability to infect CD4 lymphocytes. As viral clones become increasingly more efficient at infecting CD4 lymphocytes, the viral populations gradually increase in number. The more viruses there are, the more binding of viruses (and/or GP120) to CD4 lymphocytes occurs. CD4 lymphocytes once again commit suicide at an increasing rate. Generally, the new clones of HIV able to infect CD4 lymphocytes cause these cells to fuse together and form giant multi-nucleated cells called syncytia. The efficiency of the immune system decreases drastically as syncytia-inducing HIV appear.

Although CD8 lymphocytes attack and destroy infected CD4 lymphocytes, this only accounts for about 1 percent of the CD4 cell loss each day. Most of the CD4 lymphocytes lost to viral (and/ or GP120) binding and subsequent formation of syncytia are not infected. The destruction of uninfected CD4 lymphocytes increasingly weakens the immune system. The weakened immune system is no longer able to check HIV or fight off opportunistic pathogens. Thus, individuals infected with the new HIV clones begin to develop severe forms of common and less common diseases. HIV infected individuals that suffer from these various diseases are said to have AIDS. Without vigorous chemotherapy, death usually occurs within a year of an AIDS diagnosis.

The diseases most frequently seen in adults with AIDS are tuberculosis induced by Mycobacterium avium or M. intracellulare (10-68 percent); Pneumocytis carinii pneumonia (14-62 percent); Candida albicans (yeast) infections of the mouth, pharynx, lungs, and vagina (10-50 percent); bacterial and viral diarrheas (45 percent); Kaposi’s sarcoma, induced by human herpesvirus-8 (5-36 percent); cold sores, induced by human herpesvirus-1 and -2 (30 percent); HIV-associated central nervous system disease (15-30 percent), which includes HIV-associated dementia (15-20 percent) and cognitive/motor disorder (30 percent); Toxoplasma gondii infections of the central nervous system (3-27 percent); cytomegalovirus (CMV) infections of the intestines and eyes induced by human herpesvirus-5 (10-25 percent) and CMV pneumonia (6 percent); bacterial pneumonias (20 percent); shingles or varicella-zoster virus, induced by human herpesvirus-3 (15 percent); Cryptosporidium-caused diarrhea (10 percent); and Cryptococcus neoformans-induced meningitis (5 percent) and pneumonia (1 percent). The percent infected varies significantly when different populations are considered. For example, about 5 percent of persons who acquire HIV through intravenous drug abuse also become infected by human herpesvirus-8, whereas more than 30 percent of those who acquire HIV through sexual intercourse become infected with human herpesvirus-8.

Origins. A growing body of evidence suggests that the virus responsible for the AIDS pandemic appeared in the 1940’s or 1950’s in one of the African countries dominated by rain forests and chimpanzees: Cameroon, Gabon, Congo, or Zaire (now Democratic Republic of Congo). HIV-1 arose when a chimpanzee retrovirus, simian immu-nodeficiency virus (SIVcpz), infected a human. As HIV-1 spread, it evolved into ten distinct subtypes, designated MA through MJ. The viruses responsible for the AIDS pandemic belong to the “major” group of HIV-1, designated HIV-1:M. One of twelve hundred frozen blood samples taken in 1959 from a native of Zaire was positive for antibodies against HIV-1 and contained a portion of the viral hereditary information. Analysis of this information suggests that the virus existed just after HIV-1 began to diverge into distinct subtypes. The 1959 virus is most closely related to HIV-1:MD subtype but is also very closely related to HIV-1:MB and HIV-1:MF.

During the early 1970’s, some of the evolving subtypes became established in prostitutes along the highways that link Zaire to East African countries. Truckers and military personnel spread HIV-1:MA, HIV-1:MB, HIV-1:MC, and other subtypes from Zaire into Uganda, Rwanda, Burundi, Tanzania, and Kenya. The HIV-1:MC subtype spread north from Kenya into Ethiopia and south from Tanzania into Zambia. In the 1990’s, HIV-1:MC was most frequently detected in heterosexuals of South Africa. At about the same time, subtype HIV1:MD spread from Zaire as far west as Senegal. In the early 1970’s, subtype HIV-1:MB spread from central Africa to Europe and to the United States, where it became the predominant subtype among men who have sex with men (MSM). Thousands of men from America and Europe visited Kinshasa, Zaire, in late 1974 to view the heavyweight boxing championship bout between Muhammad Ali and George Foreman. Because of this event, HIV-1:MA and HIV-1:MB had many chances to spread to America and Europe. The first two deaths from AIDS were reported in the United States in 1978; a four-year incubation period is not unusual. In North America and in Europe, HIV-1:MB became associated with men who have sex with men (MSM). On the other hand, in South America and in the Caribbean, HIV-1:MB became dominant among heterosexuals.

In the 1980’s, various subtypes of HIV-1:M spread throughout the world. HIV-1:MA from East Africa, HIV-1:MB from North America and Europe, HIV-1:MC from South Africa, and HIV-2 from West Africa entered India to begin at least four separate AIDS epidemics. From India, HIV-1:MC spread north into China and south into Malaysia. From America and Europe, HIV-1:MB and HIV-1:MBs spread to Japan, Taiwan, the Philippines, Indonesia, and Australia. HIV-1:MB became the subtype associated with MSM, whereas the HIV-1:Bs became the subtype associated with intravenous drug abuse. A number of epidemics raged in Southeast Asia during the 1990’s. In this region of the world, HIV-1:MC and HIV-1:ME were dominant in heterosexuals, whereas HIV-1:MB and HIV-1:MBs were dominant in MSM and intravenous drug abusers.

Two strains of HIV-1 were discovered in central Africa during the 1990’s which were so different from pandemic HIV-1:M that they could not be detected by the standard antibody tests. HIV-1:O circulated in Zaire, Congo, Gabon, and Cameroon but infected only a few thousand individuals. This virus originated from another chimpanzee virus very similar to the one that gave rise to pandemic HIV-1:M. The small number of individuals infected with HIV-1:O suggested that it might have appeared in the 1980’s, but its great evolutionary distance from SIVcpz indicated that it has been around much longer than pandemic HIV-1:M (the “major” group). Possibly, HIV-1:O (the “old” group) first infected humans at the beginning of the twentieth century. HIV-1:N (the “new” group), designated YBF30, was found in Congo and Gabon. The small number of infections by HIV-1:N and the short evolutionary distance from SIVcpz suggested that this virus may first have infected humans just a little bit later than pandemic HIV-1:M. HIV-2 is closely related to monkey retroviruses that infect macaque monkeys (SIVmac) and sooty mangabey monkeys (SIVsm). It is distantly related to the retroviruses that infect African green monkeys (SIVagm) and those that infect mandrill baboons of West Africa (SIVmnd). In the 1990’s, HIV-2 was found predominantly in West Africa, from Ghana to Senegal. The variability of HIV-2 subtypes is nearly as great as that seen for HIV-1:M subtypes. This indicates that HIV-2 jumped from monkeys to humans in the late 1940’s or 1950’s. By the 1980’s HIV-2 had spread to Western Europe; it was responsible for about 10 percent of the AIDS cases in Portugal. HIV-2 also managed to reach India a few years later.

Although AIDS induced by HIV-2 usually does not develop for ten to twenty years after the initial infection, it eventually kills. HIV-2 does not spread as efficiently as HIV-1:M through heterosexual intercourse or through mother’s milk. Clearly, the infectivity of HIV-2 is much less than pandemic HIV-1:M. Nevertheless, approximately 200,000 West Africans were infected with HIV-2 during the 1990’s. In fact, HIV-2 infections out numbered HIV-1 infections in Guinea Bissau, Senegal, and Gambia. In 1992, more people were infected with HIV-2 in Guinea Bissau than in any other country. Up to 13 percent of young men between fifteen and thirty-five years of age were infected. Many people in West Africa were infected with both HIV-1 and HIV-2.

AIDS came quietly to the United States. In 1978, two men were reported suffering from multiple infections, extreme loss of weight, swollen lymph nodes, and malaise. It is estimated that these individuals were infected sometime in the early 1970’s. This was the beginning of the AIDS epidemic in the United States. By 1985, 72 percent of the AIDS cases were in gay or bisexual men, and 17 percent were heterosexual intravenous drug abusers. The incidence of new infections in the U.S. peaked in the 1980s and has held steady at approximately 40,000 to 50,000 new infections annually since the late 1990s. The incidence of AIDS diagnoses peaked in the early 1990s. Men who have sex with men (MSM) still account for the majority of new infections—approximately two-thirds in 2014.

Treatment. By 1985, researchers in France and the United States developed a test for antibodies against HIV-1. All persons diagnosed with AIDS had antibodies against HIV-1 and were presumably infected with the virus. Persons not in high-risk categories were free of the antibodies and the virus. The antibody test for HIV-1 is important because it can be used to determine if asymptomatic people are infected many years before they develop AIDS. Early treatment prevents significant damage to the immune system, inhibits the spread of HIV-1, and delays the onset of AIDS. Nearly 100 percent of those infected with HIV-1 without aggressive chemotherapy die of AIDS. A drug called azidothymidine (AZT), also called zidovudine, a nucleoside analog that blocks viral DNA synthesis, was introduced in the mid-1980’s. In most cases, AZT was found to be useful for less than six months because of its toxicity and because of the rapid rate at which the viral reverse transcriptase becomes resistant to the drug. Beginning in 1996, AZT was used in conjunction with certain other drugs that blocked viral reverse transcriptase. In 1998, the use of three-drug combinations became the norm (usually AZT, 3TC, and a protease inhibitor), effectively reducing HIV to undetectable levels in most people. The protease inhibitors blocked the viral protease needed for viral protein synthesis.

The number of AIDS cases and deaths in the United States dropped significantly after the introduction of three-drug therapy, called HAART “cocktails.” HAART stands for highly active antiretroviral therapy. The first three-drug combinations had very serious side effects. They have been improved significantly since the 1990s, such that it is now normal in the U.S. to begin treatment as soon as infection is detected rather than wait for T-cells to drop to a particular level before beginning drug treatment.

In the United States, pre-exposure prophylaxis (PrEP) was approved in 2013. PrEP is a way of preventing HIV/AIDS by allowing those in high risk groups, like MSM, to take a drug that would normally be used for treatment in order to prevent the replication of the virus if the person becomes exposed. Truvada was approved for this use in February of 2013. In 2015, there were 25,000 prescriptions for PrEP and in 2016 an estimated 79,000; the number is expected to grow.

Impact. Approximately 30 percent of babies born to HIV-infected mothers become infected. During the early 1990’s, the number of babies infected per year in the United States amounted to more than 2,000. Treating infected mothers with AZT for a month before birth reduced the number of infected babies by 67 percent. In 1999, a study demonstrated that AZT treatment of the mother combined with cesarean delivery of the baby would reduce the number of babies born to HIV-infected mothers to less than 2 percent.

Worldwide at the beginning of the twenty-first century, more than 500,000 babies were infected each year. About 300,000 of these infections could have been prevented by treating the infected mothers with AZT for a month before birth and supplying the babies with a virus-free milk substitute. Almost all nonindustrialized countries failed to provide their poor with therapeutic drugs or milk substitutes. A massive educational effort during the late 1980’s and early 1990’s alleviated the AIDS epidemics in the industrialized countries of North America and Western Europe, yet 100,000 new persons were infected during each of the last few years of the twentieth century. Male homosexual practices accounted for more than 25,000 of the new cases, whereas intravenous drug abuse was the cause of nearly 50,000. Although most older male homosexuals became monogamous and used condoms conscientiously, up to 50 percent of younger homosexuals had numerous sex partners and failed to use condoms regularly. More education might have convinced some of these young men to protect themselves by entering monogamous relationships with HIV-free partners and by using condoms conscientiously.

A number of studies demonstrated that education, drug rehabilitation programs, and the distribution of clean needles and bleach for sterilizing used needles reduced the number of persons infected by intravenous drug abuse. Education and services brought the death rates down in affluent communities in the United States; however, education, medical services, and chemotherapeutic drugs did not reach the poor blacks, Hispanics, whites, and Asians. Because these poor could not afford the $15,000-per-year treatment, their rates of infection, progression to AIDS, and death continued to increase as the twenty-first century began.

In the year 2000, four regions of the world accounted for more than 35 million (93 percent) HIV-infected persons: 25 million in sub-Saharan Africa, 8 million in Southeast Asia, 2 million in Latin America and the Caribbean, and 1 million in Asia). Each year, these four regions accounted for more than 5.5 million new infections and more than 2 million deaths.

The large number of persons infected and dying of AIDS in the twenty-first century required massive worldwide intervention by the United Nations and the World Health Organization (WHO). However, these organizations were not up to the task of saving millions because they had myriad other agendas and lacked the tremendous amounts of money needed for education, medical services, and drugs to inhibit HIV.

The Future of the AIDS Pandemic. Greed and the struggle for power played an important role in the developing AIDS pandemic. Western governments, international corporations, politicians, drug lords, and rich profiteers backed dictators, civil wars, and attacks on indigenous peoples to gain control of cheap labor, markets, and natural resources (land, wood, water, and precious metals). Western governments and corporations are particularly interested in markets. For example, in the late 1990’s, 41 international pharmaceutical companies blocked attempts by African countries to make or obtain inexpensive chemotherapeutic drugs to treat the growing number of HIV-infected persons. These companies were protecting their drug patents and royalties worth billions of dollars. The U.S. government, in support of these companies, denied preferential tariff treatment for a number of South African imports and restricted foreign aid to the country. Conflicts of interest and problems accessing pharmaceuticals are likely to remain a structural problem in the foreseeable future.