The U.S. Food and Drug Administration announced on Monday the approval of Truvada, a once-daily combination made by
Gilead Sciences, for pre-exposure prophylaxis — better known as
PrEP — to prevent sexual transmission of HIV.
"Today's approval marks an important milestone in our fight against HIV," said FDA Commissioner Dr. Margaret Hamburg. "New
treatments as well as prevention methods are needed to fight the HIV epidemic in this country."
The Centers for Disease Control and Prevention estimates that about 50,000 people are newly infected with HIV each year in the U.S. — a number that has barely budged over the past
decade — while UNAIDS estimates that there were 2.7 million new infections
worldwide in 2010.
Truvada contains two drugs, tenofovir and emtricitabine, that are
among the most widely used medications for HIV treatment. On May
10 the FDA's Antiviral Drug Advisory Committee voted decisively
in favor of approving Truvada for
PrEP based on evidence from large
clinical trials showing that it can
dramatically lower the risk of acquiring HIV via sex.
Evidence of eff ectiveness
The approval comes on the heels
of the publication of results from
three randomized, controlled PrEP
trials in the July 11 advance edition of the New England Journal of
Medicine. Findings were previously
presented at medical conferences in
2011 and early 2012.
The iPrEx trial, which enrolled
nearly 2,500 gay and bisexual men
and a small number of transgender
women in six countries (including San Francisco and Boston in
the U.S.), found that daily Truvada
reduced the risk of HIV by 42 percent overall, rising to 92 percent for
participants who had drug levels in
their blood indicating good adherence.
The Partners PrEP study, which
looked at approximately 4,700
mostly heterosexual serodiscordant couples in Kenya and Uganda,
found that the drugs in Truvada
reduced the likelihood of infection by 75 percent. Another study
of heterosexual men and women in
Africa, TDF2, showed a 62 percent
risk reduction.
The Fem-PrEP study of daily
Truvada for high-risk African women did not demonstrate a signifi cant
protective effect, but further analysis showed that participants' blood
drug levels were low despite selfreported good adherence.
In all these trials participants also
received a comprehensive package
of prevention support including
risk reduction counseling, regular
HIV and sexually transmitted infection testing, and free condoms in
addition to Truvada or placebo.
"PrEP offers a new prevention
tool for those most at risk for HIV,
and should be provided in the context of other prevention strategies,
including HIV and STI testing,
condoms, and adherence support,"
Partners PrEP principal investigator Connie Celum told the Bay Area
Reporter. "To turn the tide on the
HIV epidemic in the U.S. and globally, we need to be guided by evidence in developing our approach
to HIV prevention."
Minimizing risk
Monday's announcement came
as a surprise to many because the
FDA had extended its deadline for
a decision from mid-June to midSeptember to allow more time for
Gilead to develop a risk evaluation
and mitigation strategy to ensure
safe use of Truvada for PrEP.
Most HIV treatment advocates
applauded the approval.
"Finally, after 30 years, HIV-negative individuals have a new way to
protect themselves from becoming
infected," said Project Inform Executive Director Dana Van Gorder.
"While PrEP isn't a tool that will
be appropriate for broad use, we
are thrilled to have a new option
that could offer substantial benefi t
to those at highest risk for HIV, including gay and bisexual men and
transgender women who struggle
with consistent condom use, and
heterosexual women living in areas
with high HIV rates whose partners
refuse to use condoms."
While Truvada was shown to be
highly effective for selected high-risk
populations that use it correctly as
part of a comprehensive prevention
approach, some have raised concerns
about the diffi culty of ensuring good
adherence, side effects including kidney and bone toxicity, drug resistance,
and cost and access issues.
The FDA's decision was "reckless,"
according to Michael Weinstein,
president of the AIDS Healthcare
Foundation, the loudest critic of
Truvada for PrEP, who described
the approval as "negligence bordering the equivalence of malpractice
which will sadly result in new infections, drug resistance, and serious side effects among many, many
people."
In the clinical trials, resistance
developed in some participants
with acute HIV infection — before
standard tests can detect antibodies against the virus — who were
mistakenly classifi ed as uninfected.
Truvada alone is unable to suppress
HIV replication, allowing resistance
mutations to emerge.
To guard against this possibility,
the new Truvada medication guide
and revised prescribing information
specify that people considering PrEP
must receive a confi rmed negative
HIV test before starting the drug and
every three months thereafter.
As a condition of approval Gilead
is required to collect virus samples
for resistance testing from people
who become infected, and must
keep a record of outcomes among
women who get pregnant while taking Truvada for PrEP. The company
will also conduct a study to evaluate
drug adherence and its relationship
to side effects, seroconversion risk,
and resistance.
Next steps for PrEP
The National Institute of Allergy
and Infectious Diseases is working
with local public health departments to develop demonstration
projects that will attempt to answer
some of the outstanding questions
about PrEP.
The fi rst two programs — in San
Francisco and Miami — are expected
to start in late August, according to
Stephanie Cohen, medical director
at City Clinic, which will spearhead
the local project.
Cohen explained that the goals of
the demonstration project include
determining the level of community interest in PrEP, evaluating how
people adhere to a daily prevention
regimen in a real-world setting, collecting additional Truvada safety
data, and assessing whether and
how sexual practices change when
people know they are taking a pill
that can lower their risk of infection.
The demonstration project is
open to men who have sex with
men and transgender women who
have substantial, ongoing risk for
HIV infection. Magnet health center
and other local sites will help recruit
people for the study.
Eligible participants — who must
have confi rmed negative HIV tests
— will receive Truvada for up to
48 weeks, along with a prevention
package that includes risk reduction and adherence counseling,
condoms, and regular HIV and STI
testing.
"PrEP is an important and welcome step forward as momentum
builds for making serious headway
against HIV infection," said Judith
Aberg, chair of the HIV Medicine
Association. But she added that
implementation of PrEP "must not
contribute to HIV-related health
care disparities," noting that the
low-income and minority populations most heavily affected by HIV
are less likely to be engaged in health
care and are more likely to be uninsured or rely on Medicaid.
"We're really ushering in new
era of HIV prevention," San Francisco AIDS Foundation spokesman
James Loduca told the B.A.R. "If
we're successful in the rollout of
PrEP, the mandate for all of us is to
develop innovative programs that
can successfully deliver Truvada for
PrEP and the wrap-around medical
services it requires to hard-to-reach
communities that traditionally are
not in care."