A trial of pre-exposure prophylaxis to prevent HIV infection in Botswana is highly unlikely to show whether giving antiretroviral drugs to block infection is effective, due to a lower-than-expected rate of new infections and low retention rates, the US Centers for Disease Control announced on December 17th.
The study, TDF2, is studying whether daily dosing with Truvada (tenofovir and FTC) reduces the risk of HIV infection in young HIV-negative adults in Botswana, a country with very high HIV prevalence.
The trial is sponsored by the US Centers for Disease Control and Prevention. TDF-2, or CDC 4940, is one of several studies ongoing that are investigating the use of antiretroviral drugs as a means of blocking HIV infection (pre-exposure prophylaxis, or PrEP).
The study was originally designed to recruit 1200 participants, but investigators have now concluded that even if recruitment were doubled to 2400 participants, the study would be unlikely to show a difference in the risk of HIV infection between those who receive Truvada and the placebo group.
This is because HIV incidence in the study has been much lower than expected, due in part to declining HIV incidence in Botswana as a whole, but also due to the intensive monthly prevention counselling received by all trial participants.
The impact of widening availability of antiretroviral therapy in Botswana will be particularly difficult to quantify in the context of this study, but represents the most intriguing aspect of this announcement.
Although recent UNAIDS figures point to a number of settings where new infections are declining, it is still impossible to measure the extent to which antiretroviral treatment is reducing the rate of new infections in settings where high levels of access are being achieved, such as Botswana and Kenya.
If infection rates decline, and if accompanying prevention measures such as counselling and condom provision have a consistent impact in trials of prevention technologies such as PreP, microbicides and vaccines, future trials may need to be much larger in order to detect differences.
The power of the CDC PrEP study to detect a statistically meaningful difference has also been undermined by challenges in retaining participants in the study. Pregnancy, for example, results in suspension from the study. If participants move out of the area, or cannot attend clinic visits, they are also lost to follow-up.
CDC says that although extensive steps have been taken to overcome these follow-up problems, resulting in significant improvements in retention, numbers may still be insufficient to produce a statistically significant result after everyone has been followed for at least 12 months.
The trial will continue to evaluate the safety of Truvada as pre-exposure prophylaxis, and will also be able to report on sexual behaviour and adherence. Results are expected before the end of 2010, and results from another CDC-sponsored study, among men who have sex with men in the United States, are expected in the first quarter of 2010. South African researchers will report the results of a study using tenofovir vaginal gel to prevent HIV infection in women in July 2010.
Further information
More information on pre-exposure prophylaxis.