 TDF2
is one of several clinical trials around the world
working to identify a new strategy to reduce the impact
of HIV in Botswana and globally. The study was designed
to determine the safety and efficacy of a daily tenofovir-emtricitabine
pill (brand name Truvada) in reducing HIV infection
among heterosexual men and women in Botswana -- a
strategy called pre-exposure prophylaxis, or PrEP.
Approximately 1,200 people are enrolled in the trial.
The study is being conducted by BOTUSA, a partnership
between the Botswana Ministry of Health and the U.S.
Centers for Disease Control and Prevention.
Planned
Changes to the Study
The
TDF2 study will be adapted due to unanticipated challenges
that make it very unlikely that the trial will be
able to determine if tenofovir-emtricitabine is effective
in reducing the risk of HIV infection. The trial protocol
and timeline will be revised to focus instead on the
other remaining study questions -- primarily behavioral
and clinical safety and adherence. The study's independent
data safety and monitoring board has conducted ongoing
evaluations of safety data and has identified no safety
concerns to date.
While the trial met its original enrollment goals,
this study will not be able to determine efficacy
given much lower than anticipated HIV incidence in
the study population (likely due to declining HIV
rates in Botswana generally, and to extensive HIV
prevention services provided to all participants),
and challenges in retaining participants in this highly
mobile population of young adults.
While trial expansion was considered as a potential
solution, after a thorough analysis, CDC determined
that even with a doubling of participants to 2,400,
it would be unlikely that a valid efficacy result
could be obtained due to the lack of required retention
to date.
Low retention rates have been due to many factors,
including: participants moving out of area; pregnancies;
and time requirements that some participants felt
were too great. BOTUSA has taken extensive steps to
overcome these challenges, including adding weekend
clinic hours, increasing participant reimbursements,
and strengthening participant education and retention
procedures. While these efforts have resulted in significant
improvements in retention, a valid efficacy result
could still not be assured.
The trial, however, will provide critical information
on safety and adherence to help guide potential implementation
planning should PrEP prove effective in other trials.
CDC
has developed a proposal for how best to complete
the safety and adherence portions of the trial and
ensure necessary follow-up and communication to all
trial participants.
The original timeline for completion called for participant
involvement for 12 months after the study was fully
enrolled. It may now be possible to shorten the time
requirements for participants while still securing
the necessary data to address critical safety and
adherence questions. Proposed plans are being discussed
and finalized with the Botswana Ministry of Health,
as well as with participant and community advisory
boards. Final plans will then be submitted for approval
to the scientific and ethical review boards in Botswana
and the U.S. in January 2010.
CDC's
Partnership with Botswana
CDC
remains committed to HIV prevention research and to
its long-standing partnership with Botswana on critical
health issues. CDC expects to complete the safety
and adherence analyses from this study by the end
of 2010. CDC will also continue its nearly $60 million
commitment to the implementation of HIV prevention
and treatment services in Botswana through the U.S.
President's Emergency Plan for AIDS Relief (PEPFAR),
and will continue other research projects on TB and
HIV co-infection.
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