AIDS: A History of Treatment Modalities

The recent XVII International AIDS Conference, which ended on August 8 in Mexico City, addressed new medications that fortunate Americans have at their disposal. Indeed, medicine and pharmacology have come a long way since 1983 when concerned representatives from thirty nations met at the World Health Organization headquarters in Genera, Switzerland. That meeting was the precursor to what would eventually become the International AIDS Conferences, the first of which took place two years later in Atlanta, Georgia. In 1983, the discussions centered on questions regarding how to isolate the virus and ultimately, how to make an HIV antibody test so that "at risk individuals" could determine if they had been "exposed" to it.

When a virus enters the human body, our brilliant immune system attempts to contain it by making "antibodies". In the majority of cases, these antibodies are successful in their counter-attack and the virus is destroyed without the subject being aware that this miraculous, mini, internal war even took place. In relatively rare cases, however, the virus can out-smart the immune system which still, albeit futilely, produces antibodies. One can use an analogy of a soldier shooting at an unarmed enemy in successful cases of a destroyed virus, versus a soldier firing at an armored tank when a virus cannot be contained. In such instances, a vaccine is the only long-term, truly effective method to protect the subject by immunization.

In 1983, the medical world was eagerly awaiting the discovery of the virus and the subsequent HIV antibody test. HIV was finally isolated in 1984 as an international fury erupted over who had been the real discoverer: The National Cancer Institute in Washington, DC, or the Pasteur Institute in Paris, France. This unfortunate legal dispute delayed the development of the first antibody test until 1985 when the HIV ELIZA (enzyme-linked immunosorbent assay) test was released to the public. The controversy over who actually isolated HIV was “settled” by President Reagan who declared that both researchers had miraculously discovered it at precisely the same moment. However, most authorities maintain HIV was first isolated by the French.

During this nascent phase of understanding HIV, the first 36,000 American victims had no treatments at their disposal. As a result, there were 20,000 American deaths before there was a tool to even determine if an individual had been exposed to the virus. Terrified people afflicted with the illness, as well as their friends and family, pooled resources and raced off to Mexico, France and other countries following reports of miracle drugs and bizarre treatments. One such weird "cure" was the injection of ozone into the anus. Others attempted to kill the virus by heating the patient’s blood and re-introducing it into the body, while still others went to Israel for an ineffective drug made from egg yolks. It was not until late 1987, six years after the first patients started dying, when the beginning of scientific yet primitive treatments became available in the form of an old antiviral medication: AZT (Azidothymidine), which was eventually renamed Retrovir. The first desperate infectious disease physicians had no alternative but to prescribe it in highly toxic doses to their frantic patients.

In 1988, as the number of reported AIDS cases in America reached 86,000, public demonstrations managed to put pressure on the FDA to accelerate new drug approvals. Consequently, early treatments for the often fatal illnesses caused by HIV were discovered, notably for Pneumocystis Carinii pneumonia and CMV (cytomegalovirus), the cause of blindness and severe intestinal distress in AIDS patients. Other than AZT, no medication to actually contain the virus was available much less a vaccine.

By mid-1989, the FDA created the "AIDS Clinical Trial Information Service" so that AIDS victims and their physicians could be informed of HIV drug trials. This encouraged many patients to "take control" of their health and to seek admission into clinical trials or question their doctors about new medications. Concurrently, scientists were developing what would eventually become a major diagnostic tool to measure the virus' activity through "viral load testing" which determined how many "copies" of the virus were present in the afflicted individual's blood.

Although the ensuing years saw the development of some prophylactic medications, it was not until 1996 for important new, break-through HIV medicines to appear on the market. The FDA approved a new category of anti-retroviral (ARV) medications called "protease inhibitors" as Glaxo Wellcome's Epivir became widely prescribed. Clinical trials had demonstrated the drug’s ability to reduce the "viral load" in HIV patients. Numerous pharmaceutical companies, seeing huge profit potential, accelerated research and development of similar, expensive medications. Within months, four other large companies, Roche, Roxane Labs, Abbott Labs and Merck came out with their own protease inhibitors. As a result, "a sea change" emerged in the HIV/AIDS community that had far reaching implications. The newly prescribed combination of drugs, known as “the cocktail,” prolonged life. Many severely ill patients began to improve as symptoms lessened and they returned to some sort of normal existence. This development was not without great cost, however, both literally and figuratively. The new cocktails typically cost in excess of twelve hundred dollars a month. As one can imagine, many patients could not afford these expensive regimens while still others found the drug cocktails’ side effects very hard, or impossible, to tolerate.

By the end of last century, AIDS had killed an estimated twenty million people worldwide. In America, the face of AIDS had changed from the so-called "gay plague" to become largely an inner city catastrophe. As patients who were able to access physicians and obtain medications were living longer, infectious disease physicians were becoming experts in many medical disciplines. Given the broad spectrum of illnesses their patients were exhibiting, the partially contained virus had more time to gradually weaken its victims. A new sub-group of HIV patients called "long term survivors" had emerged.

The optimism regarding the efficacy of anti-retroviral therapy that took hold during the mid-nineteen nineties was short lived. At the International AIDS Conference in Geneva, Switzerland in 1998, the focus of the discussion centered on an alarming observation that infectious disease physicians had begun to observe called "anti-retroviral drug resistance." Drug resistance occurs when a virus begins to "mutate". Clever viruses figure out how to get around antiviral medications by transforming themselves. In the case of HIV, the mutated virus engages in a renewed attack and finds ways to enter, and destroy, the main building block of the immune system: the T-Cell. Physicians know an HIV mutation has occurred when they see a patient's viral load climbing. A complicated and expensive new diagnostic tool called "genotypic assays" or "genotyping" allows physicians to specifically determine which medication has failed and, therefore, which parts of the individual patient’s drug cocktail need to be replaced.

The result has been a plethora of new, effective medications. The few available drugs of the early 1990's have grown to dozens of medications distributed into six different "classes." For now, the new drugs are very effective and the Department of Health and Human Services' has issued new and ambitious guidelines. All treating physicians are urged to make their patients reach an "undetectable viral load" which, in turn, will keep the virus from further destroying the immune system and, hopefully, from mutating. Prior to these new classes of medications, the "undetectable" target was reached in relatively few cases.

The combined treatment called "HAART" (highly active antiretroviral therapy) is effective but complicated, costly and not without side-effects. Long term HIV survivors run risks of developing diabetes as well as cardiac, renal and hepatic problems. The official list of side effects contains fifty-one disorders, the six most common being abdominal pain, headaches, insomnia, rash, nausea and lipodystrophy (fat redistribution).

Given the current efficacy of the new medications, there is renewed optimism. However, constant viral level monitoring and an absolutely strict adherence to each patient's program are essential. Only a few missed doses can create a circumstance where the virus may mutate, the patient runs the risk of developing serious illnesses and some, or all, of the medications have to be replaced.

The current advances have been achieved through successful research and focus on anti-retroviral therapies. In so doing HIV is -- for now -- under control if the subjects are very disciplined and seen regularly by competent infectious disease physicians. It is important to remember, however, that in the history of virology, no completely successful anti-viral treatments have been effective in the long run. Only a vaccine which changes the host and renders the virus irrelevant is the real, long-term hope to eradicate AIDS.

While numerous groups around the world are researching an HIV vaccine, none have been successful. Many problems stand in the way of a vaccine including the complexities posed by HIV mutations and the ethical issues surrounding the safety of HIV vaccine trials. For the second time in as many years, and as recently as last month, one of the leading hopes for a therapeutic vaccine was, at the very least, severely delayed. A large, proposed human clinical trial to be conducted by a division of NIH (The National Institute of Health) was cancelled for security reasons. Researchers behind the previously cancelled trial had also become concerned about heightened risks. Clearly, even one highly publicized transmission of the virus during trials will severely reduce the pool of potential, HIV negative trial volunteers forever.

Unless and until a successful vaccine is discovered, the best AIDS patients and infectious disease physicians can hope for is continued containment of a deadly and clever virus through costly, complex regimes rife with side-effects both short and long term.

©2008 Richard René Silvin

Author Bio
Born in New York, from the ages of seven through eighteen, Silvin grew to adulthood within the confines of strict and homophobic Swiss boarding schools. After earning his bachelor's degree from Georgetown University (1970) and an MBA from Cornell (1972), where he also later lectured and was voted one of the most successful graduates. He spent twenty-five years as a senior executive in a New York Stock Exchange investor owned hospital company. There Silvin rose to the head of the international division of American Medical International, Inc., which owned and operated one hundred hospitals in ten countries. René lives with his beloved canine companion, T-Cell, in Atlanta, Georgia, and Palm Beach, Florida. His awards include being a Chevalier (Knight) of the Franco-Britanic Order. He has written numerous articles on hospital management and is listed in Who's Who in the World (1988), Who's Who in Finance and Industry, and Who's Who in Health Care. His book, Walking the Rainbow, is available now from Whitmore Publishing Co.