Study Published in the New England Journal of Medicine Demonstrates
the Effectiveness of a New HIV Prevention Tool, Pre-Exposure
participants who used the tablet on 50% or more of days,
as measured by pill counts, bottle counts and self-reports,
risk of HIV infection fell by 50.2% (95% CI 17.9-69.7%;
P=0.006); among those who used the pill on 90% or more of
days, as determined by the same measures, the PrEP pill
reduced infection risk by 72.8% (95% CI 40.7-87.5%; P=0.001).
Francisco, CA—November 23, 2010—In a finding with the potential
to fundamentally change strategies to slow the global HIV epidemic,
a new study called iPrEx shows that individuals at high risk for
HIV infection who took a single daily tablet containing two widely
used HIV medications, emtricitabine and tenofovir (FTC/TDF), experienced
an average of 43.8% fewer HIV infections than those who received
a placebo pill (95% CI 15.4 to 62.6%; P=0.005). The study, reported
in the New England Journal of Medicine, is the first evidence
that this new HIV prevention method, called pre-exposure prophylaxis
or PrEP, reduces HIV infection risk in people.
total of 2,499 individuals at high risk of HIV infection participated
in the six-country iPrEx study. All study participants received
a comprehensive package of prevention services designed to reduce
their risk of HIV infection throughout the trial, including HIV
testing, intensive safer sex counseling, condoms and treatment
and care for sexually transmitted infections. Half of study participants
also received the PrEP pill, while the other half received a placebo.
all, 64 HIV infections were recorded among the 1,248 study participants
who received a placebo pill, while 36 HIV infections were recorded
among the 1,251 participants who received the study drug. The
average reduction in HIV infection risk of 43.8% includes all
study participants—even those who did not take the daily pill
iPrEx study found that PrEP was more protective among those who
reported taking the pill more regularly. Among participants who
used the tablet on 50% or more of days, as measured by pill counts,
bottle counts and self-reports, risk of HIV infection fell by
50.2% (95% CI 17.9-69.7%; P=0.006); among those who used the pill
on 90% or more of days, as determined by the same measures, the
PrEP pill reduced infection risk by 72.8% (95% CI 40.7-87.5%;
pill-taking measures that rely on self-reports are not objective,
testing to measure levels of the PrEP drug in the blood of study
participants—a more reliable measure of pilltaking—also indicated
that those participants who were protected against HIV infection
were likely taking the study drug more regularly. Among a subset
of study participants who received the active drug, detectable
levels of the PrEP drug combination were found in the blood of
51% (22 of 43) of a group that remained HIV-negative, but in only
9% (3 of 34) of participants who became HIV infected. Low or absent
drug levels underlay all of the infections that occurred among
those who received active PrEP, while those who used the 2 drug
more regularly had higher levels of protection against HIV infection.
iPrEx study proves that PrEP provides important additional protection
against HIV when offered with other prevention methods such as
HIV testing, counseling, condom use and management of sexually
transmitted infections,” said iPrEx Protocol Chair Robert Grant,
MD, MPH of the Gladstone Institutes and the University of California
at San Francisco. “As with other prevention methods, the greatest
protection comes with consistent use. I hope this finding inspires
a renewed commitment from communities, industry and government
to stop the spread of HIV.” “iPrEx is a significant advance in
HIV prevention,” said Javier R. Lama, MD, MPH, the co-chair of
the study protocol who is based in Lima, Peru. “Thanks to the
extraordinary efforts of our study participants, their families
and communities, iPrEx shows that a preventive drug can significantly
reduce HIV infection risk. Further research is now needed to optimize
the efficacy of oral PrEP based on iPrEx results”.
iPrEx and PrEP
The iPrEx study (Iniciativa Profilaxis Preexposicion or Prexposure
Prophylaxis Initiative) (http://www.iprexnews.com), is a double-blind,
placebo controlled Phase III clinical trial that began in 2007
following three years of community consultation. iPrEx is the
first human efficacy study of PrEP to report data. The iPrEx study
was sponsored by the U.S. National Institutes of Health (NIH)
through a grant to the Gladstone Institutes, a non-profit independent
research organization affiliated with the University of California
at San Francisco. Additional support for iPrEx was provided by
the Bill & Melinda Gates Foundation.
devastating impact of HIV continues to spread around the world,"
said R. Sanders Williams, M.D., president of the Gladstone Institutes,
which coordinated the iPrEx study. "Gladstone will continue its
research into new ways to prevent HIV infection, and we urge community
organizations and governments to make available effective scientific
advances to stop HIV such as PrEP."
In all, 2,499 men and transgender women who have sex with men
(MSM) at high risk for HIV infection participated in the iPrEx
study at 11 sites in Brazil, Ecuador, Peru, South Africa, Thailand
and the United States. Other studies of PrEP are currently underway
among heterosexual men and women, serodiscordant couples and injection
drug users. iPrEx researchers are careful to point out that those
trials should continue, as results from the iPrEx study cannot
be extrapolated to predict the impact of PrEP on other populations.
Approximately 20,000 participants are currently or expected to
be enrolled in PrEP trials worldwide. PrEP was previously demonstrated
to be highly effective in animal studies.
In July, 2010, a study known as CAPRISA 004 found evidence that
a topical gel containing 1% tenofovir helped reduce HIV negative
women's risk of HIV infection via vaginal sex. The topical gel
is another form of HIV prevention using antiretroviral drugs currently
being explored, in addition to oral PrEP.
The drug used in the iPrEx study, a single-tablet combination
of emtricitabine (FTC 200 mg) and tenofovir (TDF 300 mg), is marketed
by Gilead Sciences, Inc. under the brand name Truvada®, and is
available generically in many countries at prices as low as approximately
40 cents (U.S.) per tablet in the poorest countries of the world.
Gilead Sciences provided 3 study drug for, but did not participate
in any other way in the design, implementation or analysis of
the iPrEx study.
and international health authorities and regulatory bodies must
now meet to review the iPrEx study data and to determine whether
and how to recommend use of PrEP for people at increased risk
of HIV infection. Much remains to be learned about how to maximize
the impact of PrEP and use this new tool most effectively. An
18-month “open label” study of FTC/TDF PrEP, which will provide
the drug to HIV uninfected participants in the original study
who wish to join, will begin next year and should provide additional
information on efficacy, safety, behavior and pill taking. HIV-positive
iPrEx participants will also be invited to enroll in this phase
of the study for ongoing monitoring.
impact of HIV on MSM
iPrEx studied the impact of PrEP on one of the populations hardest
hit by the global HIV epidemic, men and transgender women who
have sex with men (MSM). Globally, even in regions with generalized
HIV epidemics such as Africa and Asia, MSM often have much higher
rates of HIV infection than the population at large. HIV prevention
tools that reduce infection in MSM not only have the potential
to save thousands or millions of lives directly, but could also
greatly reduce the impact of HIV on all communities at risk by
reducing overall prevalence of the disease and thus the global
risk of HIV infection.
iPrEx is one of the largest HIV prevention clinical trials to
focus on men who have sex with men, the first HIV prevention study
to focus on MSM to be conducted in either Africa or Asia, and
the first demonstration of a biomedical intervention to prevent
HIV infection in MSM. Side effects, resistance and behavioral
issues in iPrEx Side effects from use of the PrEP pill were mild
and infrequent in the iPrEx study. These included a small number
of reports of low-grade transient nausea, which dissipated after
several weeks. Such symptoms are relatively common after initiation
antiretroviral therapy, and reassurance from peers and providers
in the first few weeks is important to promote long term adherence.
In addition, isolated mild elevations of creatinine, a naturally
occurring molecule filtered by the kidneys, occurred in a small
number of individuals receiving the active drug and resolved spontaneously
or with discontinuation of the pill. Slight increases were also
detected in headache and unintentional weight loss among participants
in the study arm that received FTC/TDF.
iPrEx study carefully monitored for any indications of HIV drug
resistance among individuals who became HIV infected during the
study. No iPrEx study participant developed detectable resistance
to tenofovir (TDF), one of the component drugs of the PrEP pill
used in this study. Two participants who received the active PrEP
drug developed resistance to the its other component drug, emtricitabine
(FTC), and one participant who received placebo appears to have
been infected with a strain of HIV that was already resistant
to FTC. All three participants with FTC resistance were HIV-infected
at the time of enrollment in iPrEx, but their infection was too
new to be detected by standard HIV antibody testing. Investigators
emphasize the need for additional testing and clinical screening
to ensure that anyone starting PrEP is not already HIV infected.
concern that the use of the PrEP pill could cause study participants
to relax their use of safer sex practices was not demonstrated
in the iPrEx study. In fact, self-reported HIV risk behavior decreased
among participants in both arms of the study, and condom use 4
increased. More research is needed to see how risk behavior may
change now that information is available about PrEP safety and
data from the iPrEx study will be collected, analyzed and released
in the coming year. This will include analyses designed to detect
any low level side effects related to bone mineral density or
kidney function, which have been associated with some HIV therapies.
Other analyses will search for any additional evidence of drug
resistance, look for evidence of use of the PrEP tablet through
measures of drug exposure and will examine HIV risk behavior through
the occurrence of sexually transmitted infections.
year 2.7 million people are infected with HIV, and PrEP has the
potential to help bring those numbers down. We have a moral obligation
and a public health imperative to quickly act on these results.
The HIV prevention field and national HIV policymaking bodies,
along with WHO and UNAIDS, must promptly review the iPrEx data,
consult with both experts and affected communities and develop
clear plans and recommendations for next steps in research and
possible access to PrEP,” said Mitchell Warren, executive director
of AVAC, a global HIV prevention advocacy organization.
Mark Aurigemma; email@example.com 646-270-9451
information about the iPrEx study and PrEP:
Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men
information on PrEP from Global Advocacy for AIDS Prevention (AVAC):
Information on the iPrEx study drug, FTC/TDF: http://www.truvada.com/
the Gladstone Institutes Gladstone is an independent, nonprofit
biomedical research organization dedicated to accelerating the
pace of scientific discovery and biomedical innovation to prevent
illness and cure patients suffering from cardiovascular disease,
neurodegenerative disease or viral infections. Gladstone is affiliated
with the University of California, San Francisco.