Clinical studies of treatment with antiretroviral drugs immediately showed that their benefits are short-lived when a single drug is used alone. This short-term effectiveness results when HIV mutates, or changes its genetic structure, becoming resistant to the drug. The genetic material in HIV provides instructions for the manufacture of critical enzymes needed to replicate the virus. Scientists design current antiretroviral drugs to impede the activity of these enzymes. If the virus mutates, the structure of the virusís enzymes changes. Drugs no longer work against the enzymes, making the drugs ineffective against viral infection.
Genes mutate during the course of viral replication, so the best way to prevent mutation is to halt replication. Studies have shown that the most effective treatment to halt HIV replication employs a combination of three drugs taken togetherófor instance, a combination of two nucleoside analogues with a protease inhibitor. This regimen, called triple therapy, maximizes drug potency while reducing the chance for drug resistance. The combination of three drugs is often referred to as an AIDS cocktail. In HIV-infected patients who have undergone triple therapy, the viral loads reduced significantly, sometimes to undetectable levels. Their CD4 cell count gradually increased, and they sustained good health with no complications. With this treatment, some patients who were near death were able to return to work and normal physical activity. Triple therapy was introduced in the United States in 1996. That year AIDS deaths in the United States decreased 26 percent, the first decrease since the beginning of the epidemic. In 1997 U.S. AIDS deaths decreased by 56 percent from the year before.
Despite phenomenal success, triple therapy has some drawbacks. This multidrug therapy is quite complicated, requiring patients to take anywhere from 5 to 20 pills a day on a specific schedule. Some drugs must be taken with food, while others cannot be taken at the same time as certain other pills. Even the most organized people find it difficult to take pills correctly. Yet, just one or two lapses in treatment may cause the virus to develop resistance to the drug regimen.
Many people also find it difficult to deal with the unpleasant side effects produced by antiretroviral drugs. Common side effects include nausea, diarrhea, headache, fatigue, abdominal pain, kidney stones, anemia, and tingling or numbness in the hands and feet. Some patients may develop diabetes mellitus, while other patients develop collections of fat deposits in the abdomen or back, causing a noticeable change in body configuration. Some antiretroviral drugs produce an increase in blood fat levels, placing a patient at risk for heart attack or stroke. Some patients suffer more misery from the drug treatment than they do from the illnesses produced by HIV infection.
Perhaps the greatest drawback to triple therapy is its cost, which ranges from $10,000 to $12,000 a year. This high cost is well beyond the means of people with low incomes or those with limited health-care insurance. As a result, the most effective therapies currently available remain beyond the reach of the majority of HIV-infected people worldwide.
To decrease the toxic effects of drugs and to defer costly therapy, in 2001 United States federal health officials recommended delaying drug treatment for HIV infection in people showing no symptoms and who have been infected with HIV for more than six months. The new guidelines call for delaying treatment until an infected personís CD4 cells fall below 350 cells per microliter of blood or the HIV viral load exceeds 30,000 per microliter of blood. Evidence suggests that delaying treatment poses no harm to infected people and, in fact, benefits them by deferring the toxic side effects of the drugs.