Many HIV+ urban indigents adhere well to strict anti-AIDS drug therapies; little drug resistance fou

Most HIV-positive people who are homeless or live in low-income hotels are able
to stick to the demanding drug schedules required by combination anti-viral
therapy, a preliminary study has found. The study, led by researchers at UC San
Francisco and published in the March issue of the journal AIDS, focused on the
“urban indigent” population, in which mental illness, alcoholism and drug
addiction are common.

Thirty-eight percent of the people in the study - all on complex HIV therapy -
took more than 90 percent of their medication, as measured by self-report, pill
count and an electronic monitoring system—an “impressive level of adherence
for this population,” the study’s authors say. On average, the study subjects
took 70 percent of their pills.

Contrary to expectations, the researchers also found that among those who
failed to follow the drug regimen well, drug-resistance was rare. Many have
argued that making the advanced AIDS therapies available to a wider population
would lead to lower levels of adherence and a surge in drug-resistant virus as
a result.

As expected, the study found a very close relationship between medication
adherence and viral suppression. Levels of HIV found in the blood doubled with
every 10 percent of pills the subjects missed - the equivalent of about two
doses out of 21 a week.

“The finding that many homeless and marginally housed people adhere as well as
others to the combination protease inhibitor therapy - and that very poor
adherence may not generate drug-resistant virus - offers a new perspective for
medical providers and public health officials concerned about prescribing to
this high-risk population,” said David R. Bangsberg, MD, MPH, assistant
professor of medicine at UC San Francisco, director of the Epidemiology and
Prevention Interventions (EPI) Center at San Francisco General Hospital Medical
Center and lead author on the report in the journal AIDS.

“The common expectation has been that poor adherence would lead to drug
resistance,” said Andrew Moss, PhD, senior author of the study and professor of
epidemiology and biostatistics at UCSF.  “It may be that there is not enough
circulating drug to select for resistance in poorly adherent people. Actually,
the ‘window of adherence’ that selects for resistant virus may be much higher
than many expect.”

“We found that adherence predicted the level of virus suppression much better
than tests for resistance did, and that near perfect adherence is essential to
achieve undetectable levels of viral replication,” Moss noted.

The scientists stressed that the findings of this small study—34 people
followed for about two months - need to be confirmed in larger studies before
firm conclusions can be drawn. The study drew participants from all homeless
shelters and free meal programs in San Francisco, as well as from a random
sample of low-cost, single-room occupancy hotels in the city. A total of 2,058
people were screened; 188 were identified as HIV positive from blood tests, and
36 of these people were found to be currently on protease inhibitor therapy. Of
these, 34 agreed to participate in the study.

Participants were paid $10 for weekly visits where their drug adherence over
the preceding three days was checked both by asking them to report their
adherence, counting pills remaining from the previous supply, and by an
electronically monitored pill container which allowed maximum reliability.
People were followed for six to ten weeks.

In the AIDS paper, the researchers point out that the population of the “urban
indigent” that they studied includes homeless, people with mental illness and
those who inject illegal drugs. The researchers are now studying how these
individual factors predict adherence to therapy.

“One of our goals now is to look specifically at these subgroups,” Moss
explains, “to determine if homelessness alone, or drug use, or mental illness
predict particularly poor adherence to the drug regimen. Identifying the
predictors of non-adherence will be essential to develop programs that improve
adherence in this population.”

The team acknowledges in the paper that the very act of studying adherence may
well have increased it, and that the study looked at people for only a
two-month period after they had been on therapy for about a year. Prospective
studies will be necessary to confirm the findings, the scientists conclude.

Collaborators in the study with Moss and Bangsberg, and also co-authors on the
AIDS paper, are Frederick M. Hecht, MD, assistant clinical professor of
medicine, UCSF, AIDS program, San Francisco General Hospital Medical Center
(SFGHMC); Edwin D. Charlebois, PhD, MPH, assistant professor of medicine, EPI
Center, SFGMC, UCSF; Andrew Zolopa, MD, assistant professor of medicine,
Stanford University School of Medicine; Mark Holodniy, MD, associate professor
of medicine, also at Stanford and at AIDS Research Center, VA Palo Alto Health
Care System; Lewis Sheiner, MD, professor of laboratory medicine, UCSF; Joshua
D. Bamberger, MD, MPH, director of Urban Community Health, San Francisco
Department of Public Health; and Margaret A. Chesney, PhD, professor of
medicine and epidemiology and co-director of Center for AIDS Prevention
Studies, UCSF.

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, the UCSF Gladstone Institute
of Virology & Immunology Center for AIDS Research, and an unrestricted grant
from Agouron.