March 24, 2009

Treatment Adherence: Still Important

People who regularly miss doses of their antiretroviral (ARV) regimen have an increased risk of death, according to a study published in the April issue of the Journal of Acquired Immune Deficiency Syndromes.

When combination ARV therapy was introduced in 1995 and 1996, it quickly became clear that a person’s ability to take all of his or her doses as prescribed was vital to the regimen’s success. Studies of patient adherence found that anything less than 95 percent of doses taken correctly substantially increased the risk of treatment failure and the development of drug resistance. More recently, however, some researchers have questioned whether the more potent and tolerable regimens available today may require less strict adherence.

To determine the impact of adherence on modern ARV combinations, Vivian Lima, PhD, from the British Columbia Centre for Excellence in HIV/AIDS in Vancouver, and her colleagues studied the medical records of 903 HIV-positive patients receiving care at a large Vancouver HIV clinic. Most of the patients were male, and 25 percent had a history of injection drug use (IDU). Roughly 65 percent started on a regimen containing a non-nucleoside reverse transcriptase inhibitor (NNRTI)—the most common being Viramune (nevirapine)—and 35 percent started regimens containing a protease inhibitor boosted by low-dose Norvir (ritonavir)—the most common being Kaletra (lopinavir plus ritonavir). Average follow-up was nearly three years.

Lima and her colleagues assessed adherence by comparing the patients’ refill records at the pharmacy. Her team found that 40 percent of the patients had adherence rates of less than 95 percent (for example, missing more than one dose per month among those taking once-daily treatment). Moreover, there was an overall decrease in adherence over time, from an average rate of 79 percent of doses in the first six months to 72 percent by the third year.

Though the overall death rate was low, Lima’s team found that people with less than 95 percent adherence were three times as likely to die from any cause. They also found that people on a regimen of efavirenz (found in Sustiva and Atripla) were nearly seven times as likely to die if they had poor adherence. It should be acknowledged that other studies have found high rates of treatment success with efavirenz, even in patients with less than 95 percent adherence.

Though the authors attempted to control for influential factors, such as CD4 count and viral load before starting ARV therapy, they acknowledge that they did not assess whether people with a history of IDU were currently active drug users. This is key, because active drug use is associated with higher mortality rates and might have influenced the study results.