Women's
PrEP Study Halted due to Disappointing Findings
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| SUMMARY:
A trial of Truvada pre-exposure prophylaxis for
women in Africa was discontinued this week after
an interim review found that the study was unlikely
to show a reduction in HIV infections. |
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By
Liz Highleyman
Family
Health International (FHI) announced
on April 18 that it will wind down the FEM-PrEP trial
of pre-exposure prophylaxis (PrEP) to prevent HIV
infection among heterosexual women.
The study was testing a combination of tenofovir
plus emtricitabine,
the 2 antiretroviral drugs in Gilead's Truvada
combination pill. Study participants were tested for HIV every
4 weeks and received risk reduction counseling and free condoms,
which they were encouraged to use along with the study medication.
FHI and trial investigators decided to halt the study after
a planned interim review by an independent data monitoring
committee indicated it was "highly unlikely" that
the study would be able to demonstrate statistically significant
evidence of effectiveness in reducing new HIV infections.
Participants have been asked to come for final study visits
and those who became infected are receiving referrals for
medical care.
Between May 2009 and February 18, 2011, the study screened
3752 women and enrolled 1951 participants in Kenya, South
Africa, and Tanzania. The planned enrolment was 3900 and the
study was scheduled to last through December 2012.
The
most common reason for exclusion was existing HIV infection,
with an overall prevalence of 21% in among women screened.
Participants reported an average 3.7 acts of vaginal sex during
the week prior to enrollment, which remained consistent during
follow-up.
Women
in the study were randomly assigned to take either Truvada
or placebo every day. A total of 56 new HIV infections had
occurred at the time of the interim analysis, according to
FHI, an approximate rate of 5% per year. The same number of
infections was seen among women assigned to take Truvada and
those receiving placebo.
About
90% of the participants remained in the study and the self-reported
Truvada adherence rate was about 95%, but this high rate may
be exaggerated. Researchers will analyze blood samples to
measure drug levels.
The
pregnancy rate during the study was also surprisingly high,
at 9%, even though women in the trial were supposed to be
using effective contraception (66% injectable, 30% oral).
Pregnancy was more common among Truvada recipients than in
the control group, which was not expected based on known drug
interactions with hormonal contraceptives or metabolic effects
of tenofovir or emtricitabine.
Pending
a final data analysis, FHI stated, "At this time, it
cannot be determined whether or not Truvada works to prevent
HIV infection in women." That is, it is too soon to declare
that PrEP definitely does not protect heterosexual women against
HIV.
These
"surprising and disappointing" FEM-PrEP results
come on the heels of the much-lauded iPrEx
trial findings announced last fall, showing that Truvada
reduced new HIV infections among gay/bisexual men and transgender
women by 44% overall, and by 73% among participants who achieved
the best adherence.
The
U.S. Centers for Disease Control and Prevention issued a "Dear
Colleague" letter cautioning against use of PrEP
for women at this time, reinforcing the agency's earlier
guidance emphasizing that the iPrEx findings only apply
to high-risk men who have sex with men. "We will not
know if PrEP is effective for women, couples, or injection
drug users until the conclusive results of this and other
trials are reported," according to the letter.
To
date it is unclear why the FEM-PrEP and iPrEx findings were
so divergent. One possible explanation is that oral tenofovir
reaches a higher concentration in rectal tissue than it does
in vaginal tissue. FHI intends to collaborate with researchers
conducting other PrEP studies to compare findings in an effort
to better understand the disparate results.
In
the meantime, the latest findings give support to researchers
and advocates who have urged caution in going forward with
widespread PrEP implementation despite the enthusiasm generated
by the iPrEx data.
4/23/11
Sources
Family Health International. FHI to Initiate Orderly Closure
of FEM-PrEP.
Press release. April 18, 2011.
K Fenton and J Mermin, Centers for Disease Control and Prevention.
Results of FEM-PrEP Clinical Trial Examining Pre-Exposure
Prophylaxis (PrEP) for HIV Prevention Among Heterosexual Women.
CDC advisory.
April 18, 2011.
