HIV/AIDS in the Year 2000 and Beyond

HIV/AIDS in the Year 2000
Excerpted from: Encyclopedia of AIDS

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Perhaps the greatest threat to global public health at the end of the twentieth century, the HIV/AIDS epidemic is a rapidly changing phenomenon. Statistics are in constant flux, and new developments unfold almost daily. Recognizing this fact, the Encyclopedia of AIDS: A Social, Political, Cultural, and Scientific Record of the HIV Epidemic has been designed specifically to provide a historical portrait and overview of the now nearly two decades of the epidemic.

Although it is continuously evolving, the HIV/AIDS epidemic also has been punctuated by major developments that have caused substantial shifts in its landscape. Among these landmarks have been the initial emergence of the epidemic in 1981, the discovery of HIV in 1983, the licensing of an HIV test in 1985, and the founding of the activist group ACT UP in 1987. The most recent such shift occurred in 1996, when the first public announcements were made at the International AIDS Conference in Vancouver about a class of drugs called protease inhibitors. Since the Vancouver conference, combinations of protease inhibitors and other antiviral drugs have been demonstrated to have dramatic effects against HIV, although they remain far from being a cure.

Raymond A. Smith
August 2000
Washington, DC

The introduction of combination antiviral therapy (also called the "drug cocktail") has proven to be one of the most important advances in the treatment of HIV/AIDS. Because it uses more than one antiviral drug at a time, combination therapy is able to suppress HIV by attacking it from multiple angles. Thus, even if one drug fails, another can continue to suppress viral replication. The most dramatic impact of the new antiviral therapies undoubtedly has been in the restoration of many people with HIV to better health; concurrently, there have been steep declines in HIV-related illnesses and deaths. Overall, progress has been so remarkable that medical professionals and patients have sometimes talked about the Lazarus Syndrome, in which people near death have seemingly "risen from the grave."

Between 1995 and 1997, AIDS death rates in the United States declined by more than two thirds, and new AIDS diagnoses were down by 30 percent. These reductions in illness and death were due largely to advances in antiviral therapy, though other factors were involved, including better preventive regimens for AIDS opportunistic infections and an epidemiological leveling-off of caseloads from the first wave of infections in the early to mid-1980s. Although in 1999 and 2000 the rate of decline began to level off and drug therapies were unsuccessful with some people, the impact of advances in antiviral treatment remains impressive. However, most patients on antiviral medications have been using them for four years or less. The long-term efficacy of these drugs, as well as the long-term impact of their side effects, remains unknown.

Although combination antiviral therapy undoubtedly has proven to be a hugely important development in the HIV/AIDS epidemic, it is now widely understood that combination therapy has distinct limits and is not a "cure" for AIDS. Perhaps the greatest disappointment in this treatment is that no person, once infected, has had HIV successfully eradicated from his or her body.

Thus HIV-positive individuals must continue to take antiviral medications for the foreseeable future, perhaps for life. Many people, however, have achieved "undetectable" viral loads, or concentrations of HIV in their blood that are below the level that blood tests can measure. However, such individuals may still have low concentrations of HIV in their blood as well as in bodily fluids such as semen and vaginal secretions, and in so-called sanctuary sites including the brain and the testes. Thus, it is still possible for people with undetectable viral loads to transmit the virus.

As of mid-2000, there was no absolute consensus about when to initiate antiviral therapy. One school of thought endorsed a "hit hard, hit early" approach, originally advocating that HIV-positive individuals start on antiviral therapy as soon as possible after initial infection. As it became clear that viral eradication could not be completely achieved, however, some clinicians became increasingly inclined toward holding off initiation of anti-viral therapy until there was evidence of moderate immune suppression. This delay is seen as a way to spare the patient from the drugs' many side effects and to keep open as many treatment options as possible for later use.

Antiviral medications for HIV require very demanding drug regimens: there are strict specifications for dosage, for schedule, and for what can be eaten and when. As well, many individuals cannot take antiviral medications because they produce hard-to-manage side effects such as nausea, vomiting, fatigue, and lipodystrophy (a disorder in which fat is distributed from the extremities to the torso and sometimes into the bloodstream, where it can cause cardiovascular disease). Others do not respond well to the treatments or their responses are limited in duration (although there is emerging evidence that when HIV rebounds in such people, it may do so in a weakened state). Still others choose to stop (or never start) treatments because of the regimen they demand and its impact on their quality of life. In recognition of these problems, research has been conducted on developing more easily administered medication regimens. In addition, some patients have experienced success with "structured intermittent therapy" in which they have been taken off of medications temporarily without causing lasting damage to their health.

Despite the difficulties associated with taking antiviral medications, strict adherence to drug regimens is important because every time HIV replicates, it may mutate. Some such mutations can make HIV less susceptible to antiviral medications and sometimes even to an entire class of such medications (a phenomenon known as cross-resistance). As the virus develops resistance, antiviral medications lose their effectiveness and viral load is likely to rise. Mutations threaten not only an individual's health, but also the public health, because people who are newly infected with a drug-resistant virus will themselves be unable to use antivirals effectively. There is also concern among researchers (as yet not conclusively proved) that someone who is already HIV-positive may be susceptible to "reinfection" with a new, drug-resistant strain of the virus. In order to promote adherence to the drug regimen, a variety of strategies have been developed, encompassing the practical (e.g., timers, beepers, and pillboxes), the psychological (e.g., counseling to reinforce the desire for better health), and the interpersonal (e.g., training partners, family, and friends on how to provide support).

In the developed world, drug assistance plans generally have provided broad access to antiviral medications. For many people in the developing world, however, the high cost of antiviral medications and the absence of an adequate health-care infrastructure make the use of combination antiviral therapy impracticable. The unavailability of such highly promising treatments in the areas of the world that have been hardest hit by the HIV/AIDS epidemic has generated a great deal of protest targeted at pharmaceutical companies and international organizations. This protest has been partially successful in attracting attention, but it remains to be seen if the social and political will exists in developed nations to carry out large-scale interventions in the developing world. Meanwhile, partly out of frustration about the inaccessibility of antiviral medications, South African President Thabo Mbeki reopened a troubling discussion in mid-2000 regarding old, thoroughly discredited theories that HIV might not be the cause of AIDS. While a huge international group of scientists quickly organized to back the enormous body of evidence that proves that HIV is the cause of AIDS, many feared that Mbeki's skepticism may feed denial about AIDS in South Africa and beyond.

Antiviral medication is now provided routinely to those who may have been exposed to HIV in health-care settings, such as by being stuck by an infected needle. Such "post-exposure prophylaxis" (PEP) also has begun to be made available to HIV-negative individuals who may have been exposed to the virus as a result of sexual activities, such as sexual assault or unprotected consensual sex with a partner of positive or unknown HIV status. The efficacy of PEP in such cases remains unknown, but it may prove to be successful under certain conditions. There also is a concern, however, that sexual risk behaviors may increase if at-risk individuals begin to view PEP as a "morning after" pill and thus a "backup plan" in case of exposure to HIV.

Antiviral medications also have shown tremendous promise in preventing new HIV infections spread from mother to child. The use of antiviral medications by HIV-positive women during pregnancy and delivery (along with the elimination of breast-feeding and, sometimes, cesarean-section delivery) has caused the number of HIV-infected newborns in the United States to decline by 74 percent since 1992. In the developing world, where a full regimen of antiviral medication is unaffordable, clinical trials are being conducted to determine more cost-effective means of using antiviral medications to prevent transmission during pregnancy and childbirth. These clinical trials, and others aimed at developing vaccines for HIV, at times have been highly controversial: detractors raise questions about the ethics of "experimenting" on the populations of other countries; supporters point out the potential benefits to the local population. In addition, many HIV-positive women in the developing world have no practical alternative to breast-feeding their babies, meaning that the benefits of preventing HIV transmission during pregnancy may be largely undone during the breast-feeding period.