(This story has been posted on The Wall Street Journal Online's
Health Blog at http://blogs.wsj.com/health.)
By Amy Dockser Marcus
The AIDS Healthcare Foundation filed a citizen's petition
yesterday asking the FDA not to approve Gilead Sciences'
antiretroviral drug Truvada for use in healthy people as a way to
prevent HIV infection.
Why? As the WSJ reports, there is debate in both the scientific
and advocacy community about whether Truvada should be approved for
use in healthy people who are at high risk of HIV infection. One of
the main studies cited in the citizen's petition highlights the
challenges of trying to assess when to use potent medications to
stave off health problems in people who aren't sick.
The study, published online last month by the journal AIDS,
involved an analysis of the electronic health records of nearly
11,000 patients by researchers at the Veterans Administration and
the University of California, San Francisco.
These were HIV patients who hadn't yet taken antiretroviral
medications. The researchers found that for each year that a
patient took tenofovir, a commonly prescribed, highly effective
antiretroviral and one of the two key components of Truvada, the
risk of kidney damage rose. The risk continued even after patients
stopped taking the drug, the researchers reported.
Michael Shlipak, chief of internal medicine division at the San
Francisco VA Medical Center and the principal investigator for the
study, points out that it's an observational study rather than a
clinical trial, making it possible that other factors besides the
drug affected the results.
But Shlipak tells the Health Blog that when he saw the results,
"my thoughts went to" the use of Truvada to prevent HIV infection.
"In HIV-infected people, the benefit of the drug is absolutely
tangible," he says. "In people who are not infected, there is a
potential benefit with what could be a clear harm."
This gets to the crux of the dilemma when prescribing medicine
for prevention: How much risk is too much and what amount of
benefit is sufficient? The answer may vary depending on the
individual. Chemoprevention of many diseases, not just HIV,
involves giving healthy people drugs for years and possibly
decades. Risks that don't initially show up in trials may arise
further down the road, researchers say.
Robert Grant, a professor of medicine at UCSF, and the chair of
a study that Gilead used in its FDA application for the preventive
use of Truvada, says the VA study was very valuable but that all of
the people in it were already infected by HIV -- significant
because the virus itself causes kidney damage. In the prevention
setting, researchers didn't see this problem, possibly because
people "don't have the double hit of HIV injury on the kidneys and
the possible effects of medication."
CDC guidelines say that HIV-negative people using
antiretrovirals for prevention should monitor kidney function every
three months. Grant supports this recommendation. In the previously
reported trials, people were HIV-negative and also had normal
kidney function. As the drug is used in the real world, there will
be people taking the drug whose kidney function is already
abnormal, Grant says, so "some additional, more intensive
monitoring is needed."
Howard Jaffe, president of the Gilead Foundation, the
philanthropic arm of Gilead Sciences, says the VA study's
conclusions are contrary to controlled trials that Gilead has
done.
"In the realm of scientific endeavor, controlled studies always
trump observed studies," Jaffe says. The results of multiple years
of controlled studies demonstrate that the VA study "overstates
some of the risks involved with tenofovir," he adds.
Shlipak says he hasn't taken a stand on whether the FDA should
approve Truvada for prevention. If it is going to be approved,
though, he says, "it should be in settings of patients with very
low kidney risk and very active kidney surveillance."
Image of HIV by C. Goldsmith via CDC
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