AIDS Patients Benefited From Molecular Findings
I was already a medical writer when the first reports of AIDS appeared in the iconic Morbidity and Mortality Weekly Report, but the dry public health language in that first report did not in any way predict the scope of the tragedy that ensued. And the tragedy continues, in this country and abroad.
In the face of that, it is easy to ignore how science changed the face and the course of this disease. In 1981, we did not even know what caused AIDS and the speculation ran the gamut, from the blame game to space aliens. Most in the world of medicine suspected that an infectious agent was at fault. It was the mid-1980s before the candidate ““ a retrovirus eventually called human immunodeficiency virus ““ was proposed by scientists in this country and France.
Retroviruses were relatively unknown, but Dr. Robert Gallo, then with the National Cancer Institute, had been investigating them for years. Even before the link between HIV and AIDS was established, he and others in the virology field began parsing the life cycle of the virus and the genes that controlled its existence, seeking a weakness that could be exploited by drugs or, even better, a vaccine.
First drug was AZT
The first drug ““ AZT or azidothymidine and now zidovudine”“ exploited the method by which the HIV reproduced by inhibiting a critical enzyme called reverse transcriptase. AZT was crude and attacked the virus at only one point in its lifecycle. It had significant side effects, and it certainly was not a cure. It did, however, offer promise that the virus could be attacked, and without killing the patient.
The attack was a rational one, based on the life cycle of HIV itself. The genetic material in a retrovirus is RNA, not the DNA that carries our genetic code and that of almost all creatures. The retrovirus uses an enzyme called reverse transcriptase to translate its genetic information from RNA into DNA. When HIV enters the cell, it carries with it molecules of reverse transcriptase. This enzyme synthesizes the DNA that enters into the nucleus of host cell where they are inserted into DNA.
AZT and other reverse transcriptase drugs halt the activity of this crucial enzyme. Developing and using these drugs required that we understand the natural history of the virus itself.
Protease inhibitors
In the mid-1990s, powerful drugs called protease inhibitors appeared on the scene. The HIV protease enzyme plays an important role in the maturation of the budding virus. Without this enzyme to cleave or cut the virus at critical points in its life cycle, the virus never matures. Protease inhibitors, as their name implies, block the protease.
Researchers designed their protease inhibitors using a three-dimensional model that helped them target the active site at which the HIV protease acted. When the first protease inhibitors were combined with other anti-AIDS drugs in a cocktail, they stopped the infection in its tracks in many people. The levels of virus in the blood dropped to near undetectable levels. Lifespans increased, and people with HIV no longer faced much shortened lives.
No cure
Highly active antiretroviral therapy or HAART, as it became known, is not a cure. In fact, there is no cure, nor is there a vaccine. Research continues, and the disease continues to infect new people, in the United States, Europe and the world.
However, on this World AIDS Day, and each day after, we should remember that the attack on HIV/AIDS has been social and political, but mostly scientific. Without the science, the death toll in this country would have continued at the appalling pace we saw in the 1980s and early 1990s. As we take this potent therapy into the Third World, it promises to make an impact there as well.
The future
The future of AIDS treatment and prevention rests with the science. It is important to keep that in mind as decisions are made about funding and where it should best be spent.
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