Most resistance to Anti-HIV drugs created by good pill-taking patients
Public release date: 20-Aug-2003

Contact: Jeff Sheehy
jsheehy@psg.ucsf.edu
415-597-8165
University of California - San Francisco

Resistance mutations to Anti-HIV medications are more likely to occur in
patients who take most of their medications than in those who take few
of them, according to researchers at UCSF

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.