Drug Resistance to Antiretroviral Therapies according to medical research usually takes place when there is a break in the use of antiretroviral drugs giving the HIV time to develop resistance. When a single antiretroviral drug is used alone, its benefits last only a short time, as clinical studies of treatments with the drugs soon demonstrated. This short-term effectiveness is due to mutation or changes in the genetic structure, of HIV that makes the virus resistant to the drug. The genetic material in HIV provides instructions for the manufacture of critical enzymes needed to replicate the virus. Scientists design antiretroviral drugs to impede the activity of these enzymes. If the virus mutates, the structure of the virus’s enzymes changes and the drugs no longer work against the enzymes or the virus.
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 for halting HIV replication employs a combination of three drugs taken together—for 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 its success, triple therapy has had some drawbacks. This multidrug therapy has been quite complicated, requiring patients to take anywhere from 2 to 20 pills a day on a specific schedule. Some drugs must be taken with food, and some cannot be taken at the same time as other pills. Even the most organized people find it difficult to take the pills correctly. Yet, just one or two lapses in treatment may cause the virus to develop resistance to the drug regimen.
In July 2006 the FDA approved a new three-drug combination that can be taken as a single pill once a day with or without food. Marketed under the name Atripla, the new drug combines the existing drugs Sustiva (the NNRTI efavirenz) and Truvada (the NRTIs emtricitabine and tenofovir) in a special formulation. The product is seen as a breakthrough in AIDS and HIV treatment for its simplicity and convenience. The once-daily pill form should help patients take the drugs on a regular, uninterrupted schedule that will not allow the HIV in their bodies to develop resistance to the drugs. The new pill could prove particularly useful in developing countries, where following complex regimens of different AIDS drugs is often impractical.
Many people 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 has been its cost, which has ranged 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 have remained 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 person’s CD4 cells fall below 350 cells per micro-liter of blood or the HIV viral load exceeds 30,000 per micro-liter 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. Drug Resistance to Antiretroviral Therapies is however a serious concern to medical practitioners who are working hard to advice patients to take their drugs regularly.