Study identifies predictors of HIV drug resistance in patients beginning triple therapy

The best method for preventing HIV patients from developing drug resistance is a careful, dedicated adherence to their prescribed drug regimen, according to a long-term, large-scale study presented today in New York City at the American Medical Association Media Briefing, HIV/AIDS, The Drug Resistance Epidemic. Other key predictors of resistance include measures of how much virus was present in a person’s bloodstream at the start of therapy and how much their immune status was compromised.

“We have a lot of studies showing that triple therapy works, as well as a lot of good information on the problem of resistance developing in triple antiretroviral therapy,” said Richard Harrigan, Ph.D., director of the British Columbia Centre for Excellence in HIV Research Labs at St. Paul’s Hospital in Vancouver and lead author of the paper. “The problem with past studies is that they were limited to people in clinical trials and as people drop out they are lost to the study. In this study, we followed people beginning initial triple therapy for 30 months and were able to really get a sense of how the therapy works outside of clinical trials.”

Triple therapy for HIV/AIDS is designed to hit the virus with three or more antiretroviral drugs from two or more different classes at once in order to reduce the viral load (amount of virus circulating in the blood) so drastically that the virus is not replicating enough to mutate and become resistant to the drugs designed to fight it, Dr. Harrigan explained.

Researchers in the study, published in the Feb. 1, 2005 issue of the Journal of Infectious Diseases, followed more than 1000 people who were beginning HIV triple therapy for the first time through 30 months of treatment. A number of factors, including adherence to their prescribed medication regimen, age, gender, plasma viral load, CD4 count, year of initial therapy and history of injection drug use were examined for their impact on the development of resistance.

Of all the factors studied, adherence to the medication regimen (measured by the number of filled prescriptions) had by far the greatest impact on the development of resistance, the study showed. To test adherence, patients were divided into groups according to what percentage of their prescriptions they filled, 0-20 percent, 20-40 percent, 40-60 percent, 60-80 percent, 80-90 percent, 90-95 percent and 95 percent or more. Patients who missed less than five percent of their medications did not develop resistance over the course of the study.

“Those who took 80 percent of their medication were likely to develop resistance most quickly. This probably means that they are taking enough medication to create a selective pressure,” Dr. Harrigan said. “Which means that resistant virus mutations still have an opportunity to replicate instead of reducing the viral load to levels so low it can’t replicate at all.”

“The good news is that although they require a very high level of adherence, these therapies do work,” Dr. Harrigan said. “And things have only gotten better in the time since this study was completed. We have more and better drugs and a better understanding of how to give them. We are working to make taking them as simple as possible.”