Imperfect Adherence to HAART Fuels HIV Drug Resistance

By Megan Rauscher

Among antiretroviral-naïve HIV-infected adults starting highly active antiretroviral therapy (HAART), less than perfect adherence to medication and high plasma HIV load at baseline are major predictors of the development of drug-resistance mutations.

These are the results of a retrospective, longitudinal analysis presented in New York City Thursday at the American Medical Association Media Briefing "HIV/AIDS: The Drug Resistance Epidemic." The findings are also published in the February 1st issue of The Journal of Infectious Diseases.

Dr. P. Richard Harrigan from the British Columbia Centre for Excellence in HIV/AIDS in Vancouver and colleagues evaluated drug resistance in all 1191 HIV-1-infected ART-naïve adults initiating HAART in British Columbia between August 1, 1996 and September 30, 1999. These individuals make up the HOMER (HAART Observational Medical Evaluation and Research) cohort.

Two hundred ninety-eight subjects (25%) developed drug-resistance mutations during follow-up, which is in line with previous reports.

"If one looks systematically, approximately one third of patients starting HAART will have developed some degree of HIV drug resistance over the first 2.5 years of therapy," Dr. Harrigan told Reuters Health.

There was little difference in time to resistance whether one started with an initial protease inhibitor-based regimen or an initial non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen, he also reported.

Of all the factors studied, adherence to medication had the greatest impact on the development of drug resistance.

Patients with prescription refill percentages in the 80%-to-90% range were more than four times more likely to develop drug resistance (hazard ratio of 4.15) than those with prescription refill percentages of 0% to less than 20%. Those with medication refill percentages of 95% or higher did not develop resistance during the study period.

This study shows that "people who are doing what is actually a pretty reasonable job of adhering to therapy -- they are taking most of their medication -- have the highest risk of developing resistance," Dr. Harrigan noted.

"The lowest risk was in those who religiously picked up their medication and consistently had good levels of the drugs in their bloodstream, [and] managed to suppress their virus well," he added.

Another important predictor of the development of drug-resistance was plasma HIV level at the start of therapy. The multivariate hazard ratio for resistance was 1.59 in subjects with high baseline plasma viral loads.

"This implies that the HIV drugs were not sufficient to completely shut down virus replication in these individuals who had very high amounts of virus, and that one should be most wary of potential resistance problems in those with high viral loads," Dr. Harrigan said.

01/19/05

J Infect Dis 2005;191:339-347.