Most resistance to anti-hiv drugs created by good pill-taking patients -- not by poor pill-takers

Resistance mutations to anti-HIV medications are more likely to occur in patients who take most of their medications rather than in those who don’t, according to AIDS specialists at the University of California, San Francisco.

“These findings will make us rethink the argument that life-saving antiretroviral drugs should be denied to some populations because poor pill-taking behavior might accelerate the creation of resistant mutations of the HIV virus,” said the study’s lead author, David R. Bangsberg, MD, MPH., director of the UCSF Epidemiology and Prevention Interventions (EPI) Center at San Francisco General Hospital Medical Center (SFGHMC).

In a study of patients on antiretroviral drugs, resistance mutations were twice as likely to occur in patients who took 80 percent or more of their antiretroviral medications as they were in patients who took 40 percent or less, according to the researchers.

“Ironically it is the ‘good adherers’ who developed more resistance, rather than the ‘problem patients’,” said study co-investigator Andrew Moss, PhD, professor of epidemiology and medicine.

“You need pressure from antiviral medications for resistance to develop. What is surprising is that what we typically take to be excellent pill-taking—80 percent of pills or better—leads to more resistance than occasional or inconsistent pill-taking. A caveat—this does not mean patients should take less of their drugs to avoid creating resistance. Good adherence to the antiviral regimens still is the best bet to prevent becoming ill or dying with HIV/AIDS. Many patients with excellent, even perfect, pill-taking are living longer with resistant virus, than those who do not take enough medication to select for resistant virus,” said Bangsberg.

The study, appearing in the September 5, 2003, issue of AIDS, looked at 148 participants from the Research on Access to Care in the Homeless (REACH) cohort, a systematic sample of HIV-positive adults recruited from homeless shelters, free meal programs, and low-income single-room-occupancy hotels in San Francisco. The participants, who consented to unannounced pill counts to measure adherence, were all on anti-HIV regimens taking three or more antiretrovirals.

Pill counts were conducted, unannounced, every three to six weeks over a 12-month period at the participant’s usual place of residence. Blood was drawn monthly and tested for levels of HIV virus. Blood specimens were also analyzed for drug resistant mutations using genotype tests.

Participants in the top two quintiles of adherence, who took 80 percent or more of their medications, accounted for more than half of all new drug resistance mutations occurring in the study. Those in the next two quintiles, who took between 42 percent and 78 percent of their medications, had 35 percent of the new mutations. Only 12 percent of the new drug resistance mutations were found in the participants in the lowest adherence quintile, those who took less than 41 percent of their medications.

Co-authors of the study are Edwin D. Charlebois, MPH, PhD, UCSF assistant professor of medicine, and David Guzman, senior statistician, both at the UCSF EPI Center at SFGHMC; Robert M. Grant, MD, MPH, assistant investigator at the Gladstone Institute for Virology and Immunology and UCSF assistant professor of medicine; Mark Holodniy, MD, director of The HIV Research Center at the VA Palo Alto Health Care System; Steven G. Deeks, MD, UCSF associate professor of medicine in the Positive Health Program at SFGHMC; Sharon Perry, PhD, post doctorate fellow in infectious diseases, Kathleen Nugent Conroy, graduate researcher, and Andrew R. Zolopa, MD, assistant professor of medicine, all in the Stanford University School of Medicine; and Richard A. Clark, senior public administrative analyst in the UCSF Department of Epidemiology and Biostatistics at SFGHMC.

The study was funded by the National Institute of Mental Health, the University-Wide AIDS Research Program of the State of California, the AIDS Clinical Research Center of the University of California, and the UCSF/Gladstone Institute for Virology and Immunology Center for AIDS Research. Bangsberg received additional funding from The Doris Duke Charitable Foundation. Viral load test kits were donated by Roche.

The EPI Center and the Positive Health Programs are programs of the UCSF AIDS Research Institute.

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