June 26, 2013
Bangkok, Thailand/New York, N.Y. -- On June 12, results from an efficacy trial of tenofovir as pre-exposure prophylaxis (PrEP) against HIV infection in individuals with a self-reported history of injection drug use were published in the Lancet. The trial was sponsored by the U.S. Centers for Disease Control and Prevention (CDC) and took place in Bangkok, Thailand (named the Bangkok Tenofovir Study). The publication was accompanied by a flurry of press releases and drew considerable news coverage due to the documentation of a statistically significant reduction in risk of HIV acquisition of 48.9%.
Not mentioned, however, were serious concerns about the conduct of the trial raised by several Thai community groups -- including the Thai Drug Users Network (TDN), the Thai National Network of People Living with HIV (TNP+), and the Thai AIDS Treatment Action Group (TTAG) -- and the disheartening unwillingness of the researchers to respond to those concerns:
Paisan Suwannawong, executive director of Thai AIDS Treatment Action Group (TTAG) and cofounder of Thai Drug User's Network (TDN), said:
While TTAG is glad for any evidence of reduced HIV transmission among people who inject drugs, this trial failed to promote basic ethical practices and patently ignored community concerns. In our opinion, the trial serves as a "worst practice" example of community engagement, failing to ensure participant access to a comprehensive prevention package in a placebo trial, and ignoring other issues we tried to raise to researchers at the outset.
Beyond these specific issues, the applicability of the trial results to real-world PrEP use by injection drug users is also rendered uncertain by the provision of financial reimbursement to trial participants for attending study visits and the high proportion of doses (>85%) administered under direct observation.
Moreover, the extent to which tenofovir protected against parenteral versus sexual exposure is unknown: no efficacy was seen during the first three years of the trial when reported needle use was highest, and the incidence rates between the study arms only bifurcated during the last four years as the total number of participants dwindled, and needle use and needle sharing declined to very low levels. In a commentary accompanying the paper in the Lancet, Salim Abdool Karim notes, "it is not possible to make definitive conclusions about the efficacy of daily tenofovir for the prevention of parenteral transmission of HIV from these data."
The results from the Bangkok Tenofovir Study add to the existing evidence that antiretrovirals can prevent HIV transmission, but are subject to many limitations. The trial could have been greatly improved if community engagement had taken place during the planning stages, rather than after approval of the protocol by regulatory bodies. The presentation of the trial to community advocates after the fact, when opportunities to alter the design were extremely limited, was widely viewed as an act of bad faith and set the stage for the unproductive dialogue that followed.
Future biomedical prevention trials need to heed the lessons of the Bangkok Tenofovir Study and ensure extensive community consultation and full respect for the rights of research participants.
Kaplan K. Chapter 4: The Thailand story. In: Oral tenofovir controversy II: voices from the field. Lagos: New HIV Vaccines and Microbicides Advocacy Society; 2009 July 22. p. 3641. Available from: www.nhvmas-ng.org/publication/TDF2.pdf. (Accessed 2013 June 12)
Jintarkanon S, Nakapiew S, Tienudom N, Suwannawong P, Wilson D. Unethical clinical trials in Thailand: a community response. Lancet. 2005 May 713;365(9471):16178. doi:10.1016/S0140-6736(05)66501-4. Available from: www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)66501-4/fulltext. (Accessed 2013 June 25)