Acquired immune deficiency syndrome
Cocktail approach to treatment
At present no vaccine exists to protect against infection, although recent advances have led some experts to predict that a vaccine should be available within the next ten years. Obstacles still remain, however, primarily because of the variability of the virus itself. Many different strains of HIV exist, and even within a given individual's body the virus can undergo mutations rapidly and easily. A number of candidate vaccines were in the early phases of testing in human volunteers by the early 1990s around the world. In 1998 a vaccine developed from two HIV strains common in North America was approved by the U.S. Food and Drug Administration (FDA) for human trials in people at high risk for exposure to the virus. The trials will take place in the United States, Canada, and Thailand.
Progress is also being made in the treatment of HIV infection. The focus has been on two major areas: antiviral drugs with a direct effect against the causative agent; and immunomodulators, or substances that act to reconstitute or enhance immune-system function. Efforts to develop and improve treatments of specific opportunistic infections and tumors continue, and more new drugs have been approved.
Because of the complex life cycle of HIV, however, the successful development of antiviral and immune-enhancement therapies represents an enormous scientific challenge. Unlike most known disease-producing microorganisms, HIV infects the very cells that are intended to lead the immune system's attack against invaders. This makes it technically very hard to kill the virus without destroying the already-threatened immune system. Furthermore, there may be several important reservoirs in the body for HIV that will be difficult to deal with while not causing fundamental damage to the host cells involved. For example, circulating blood cells of the kind called macrophages can support HIV replication while harboring the virus from the body's immune surveillance; macrophage cells appear to play an important role in the propagation of HIV throughout the body, including the brain.
In seeking effective therapies, other important considerations are involved. Thus, since the brain is an important target of HIV infection, an effective anti-HIV agent should be able to cross the blood-brain barrier (see brain).
It would also be desirable if therapies could be taken orally, since it is likely that AIDS drugs would have to be taken for a long period and perhaps a lifetime. Dozens of agents have been tested in humans, and 11 have been licensed by the FDA: azidothymidine (AZT), dideoxyinosine (ddI), dideoxycytidine (ddC), dideoxydidehydrothymidine (d4T), lamivudine (3TC), saquinavir, virosept, ritonavir, crixivan, delavirdine, and nevirapine.
Each of these drugs acts differently, and they have been found to be very effective when taken in combination (nicknamed the "drug cocktail") with one another, rather than as separate medications. For example, AZT interferes with virus replication and has been found to prolong life in some patients, but its ability to delay the onset of full-blown AIDS in persons with no symptoms has been questioned. The drugs ddI, ddC, d4T, and 3TC are in a class that works well with AZT because they do not produce the same side effects. With more people using the drug cocktail over a longer period of time, researchers have noted that its effectiveness can decrease. However, there are other drugs in clinical trials. In addition, many drugs are available to treat the opportunistic infections that are part of AIDS.
The slow process of FDA approval of new AIDS drugs has developed into a political issue. AIDS activists are demanding that the government speed up authorization by postponing certain tests comparing efficacy and ability to prolong life until after the drug is on the market. While a faster approval rate may expose patients to unforeseen side effects, activisargue that patients with life-threatening diseases who have no alternative therapy should still be entitled to choose these drugs.