Complete Adherence to Antiretroviral Drug Regimens Best Way to Avoid Development of Drug-Resistant HIV, Study Says

Complete adherence to antiretroviral drug treatment is the best way to prevent HIV from mutating and developing drug resistance, according to a study to be published in the Feb. 1 issue of the Journal of Infectious Diseases that was presented on Thursday at an American Medical Association briefing, Reuters reports (Reuters, 1/13). Richard Harrigan and colleagues at the Vancouver, Canada-based British Columbia Centre for Excellence in HIV/AIDS studied 1,191 HIV-positive individuals who began antiretroviral treatment between 1996 and 1999 and continued taking medication for up to three years, according to the Miami Herald (Tasker/Goldstein, Miami Herald, 1/14). The researchers found that 298 of the individuals developed drug-resistant HIV over the first 2.5 years of therapy, according to Reuters Health. There was "little difference" in time to resistance between individuals who took a protease inhibitor-based regimen and people who took a non-nucleoside reverse transcriptase-based regimen, according to Reuters Health. The researchers determined that adherence to therapy had the "greatest impact" on the development of drug resistance, Reuters Health reports (Rauscher, Reuters Health, 1/13). Individuals who took their medication about 80% of the time were four times as likely to develop drug resistance as people who took all of their pills, according to the study, the Herald reports (Miami Herald, 1/14). Patients who missed less than 5% of their medications did not develop resistance during the study period (AMA release, 1/13). "The results prove HIV drug regimens are nothing like a game of horseshoes -- close is not good enough," Harrigan said, adding, "It's very risky to pick up your drugs and take them inconsistently" (Lee, Vancouver Sun, 1/13). He added, "The good news is that although they require a very high level of adherence, these therapies do work" (AMA release, 1/13).

Viral Load
Baseline viral load measurements are another "important predictor" of the development of drug resistance, the study found, according to Reuters Health. Individuals with high viral loads at the beginning of therapy were 59% more likely to develop drug resistance than people who had lower viral load levels before beginning treatment, according to the researchers, Reuters Health reports (Reuters Health, 1/13). "If you've got higher levels of virus in your bloodstream, you're more likely to pick up resistance," Harrigan said, adding, "This tells us that even though these drugs are doing a great job in terms of keeping people alive, they are not able to completely shut down the virus from replicating."

Reaction
Harrigan said that the study shows that patients need to be "mentally, as well as physically, ready before starting a drug regimen" in order to maintain complete adherence, according to the Sun. "If you're not going to do it right, you should probably wait -- if you can," Harrigan said (Vancouver Sun, 1/13). Dr. John Bartlett, director of the HIV Care Program at Johns Hopkins University School of Medicine, said the study shows that antiretrovirals are "not like a blood pressure pill, where if you miss one day your pressure will go up, but it will go back down when you take it the next day," adding that because HIV mutates quickly, "if you miss pills, you don't get the advantage of taking them later." Dr. Kathleen Squires, associate professor of medicine at the University of Southern California Keck School of Medicine, said that doctors should monitor patient's antiretroviral regimen compliance, adding, "You'll never find out whether the patients are taking the drug if you don't ask them," according to the Herald. Dr. Charles Mitchell, an infectious disease expert at the University of Miami, said that patients who become resistant to first-line antiretroviral therapy often later are prescribed "more complicated" second-line regimens that require more pills with even more side effects to be taken more often, according to the Herald. "You're taking patients that had problems with adherence to begin with and you're giving them more complex regimes," Squires said, adding, "That's a conundrum" (Miami Herald, 1/14). Study co-author Zabrina Brumme said that the researchers plan to continue to follow study participants for another two and a half years, the Sun reports (Vancouver Sun, 1/13).

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