Imperfect adherence to HIV therapy fuels resistance

Among HIV-infected adults who have not been previously treated with HIV drugs who start on highly active antiretroviral therapy (HAART), less than perfect adherence to medication schedules and high levels of HIV in the blood before therapy are two major predictors of drug resistance.

These are the results of a study presented in New York City on Thursday at the American Medical Association Media Briefing "HIV/AIDS: The Drug Resistance Epidemic." The findings are also published in 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-infected adults beginning HAART in British Columbia between August 1, 1996 and September 30, 1999.

Two hundred ninety-eight subjects (25 percent) developed drug-resistant virus 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," Harrigan told Reuters Health.

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

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

The findings revealed 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," Harrigan noted.

Patients with prescription refill rates between 80 and 90 percent were more than four times more likely to develop drug resistance than patients who refilled less than 20 percent of their prescriptions. Those with medication refill percentages of 95 percent or higher did not develop resistance during the study period.

"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 blood levels of HIV at the start of therapy. Patients with high blood levels of HIV at the start of therapy had a 59-percent increased risk of developing drug resistance.

"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," Harrigan said.

SOURCE: The Journal of Infectious Diseases, February 1, 2005.