Biomedical Research in Developing Countries - UNICRI

very critical and difficult to ensure.
The Tenofovir Oral HIV Prophylaxis Trials 40 , sponsored by the CDC and conducted
in the United States, Botswana and Thailand provide another example of the critical
issues surrouding clinical trials conduct. The trials, initiated in the USA and
Thailand in 2005 and in Botswana in 2007 were supposed to last from four to six
years. The studies were designed as an interventional, randomized, double blind
and placebo controlled of pre-exposure prophylaxis, or PrEP, for HIV prevention.
The study hypothesis tested the safety and efficacy of oral daily administration of
the antiretroviral drug tenofovir disoproxil fumarate used alone or in combination
with emtricitabine to prevent HIV transmission among three populations at high
risk for infection: heterosexuals in Botswana, injection drug users in Thailand, and
men who have sex with men (MSM) in the United States. The study envisaged a
total enrollment of 4,000 participants divided as follows: 1,200 in Botswana, 2,400
in Thailand and 400 in the USA. The study design was also different among the
sites. The Botswana and Thailand study tested the safety and the efficacy of the
therapy, while the USA was an extended safety trial. Similar PrEP trials were also
conducted in 2004 in Ghana, Cameroon, Nigeria and Cambodia by Family Health
International (FHI), with funding from the Bill and Melinda Gates Foundation to
show that tenofovir as a preventive drug was both safe and acceptable for use by
HIV-negative individuals. Except for the study in the USA, all the tenofovir trials
have been progressively terminated or halted and put under scrutiny at various
stages due to pressure from civil society, patient’s organizations and the media.
Although the efficacy of antiretrovirals has been shown to effectively reduce HIV
transmission from infected mothers to their children during labor and delivery and
in newborns by 50% as well as to reduce the risk of infection from accidental
exposure in health workers by 80%, only data from animal studies are currently
available that show tenofovir and tenofovir plus emtricitabine are effective in
reducing the transmission of HIV-like viruses after a single exposure in healthy
animals.
Tenofovir was approved in the USA in 2001 (brand name Viread®) for the treatment
of HIV infection, while the combination pill tenofovir plus emtricitabine (together,
known as the brand name Truvada®) was approved in 2004. According to the CDC,
more than 200,000 HIV infected people currently use these drugs worldwide.
Currently, tenofovir (and the combination pill) is considered the best candidate for
preventive HIV therapies in high risk infection settings, due to its safety profile,
with a relatively low level of side effects and a slow development of resistance, as
compared to other antiretrovirals. The oral administration, once a day, with or
without food, make it the most current convenient to use also in difficult clinical settings.
All the cited tenofovir PrEP studies had undergone review and approval by sponsor
40 http://www.cdc.gov/hiv/resources/factsheets/prep.htm (accessed in October 2008)
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