But the devil’s in the details.

Just 2 months after the use of oral tenofovir was discontinued in the VOICE trial , study investigators have announced that the use of vaginal tenofovir gel is also being discontinued. The decision is based on an interim review at 2 years, showing similar rates of HIV acquisition in women assigned to a daily tenofovir-based vaginal microbicide and those assigned to placebo gel (6.0% and 6.1%, respectively). Notably, the review did not identify any safety concerns.

The VOICE trial originally included five study arms — oral tenofovir (Viread), oral tenofovir/FTC (Truvada), oral placebo, vaginal tenofovir gel, and vaginal placebo gel — with each intervention prescribed for daily use. About 1000 HIV-uninfected women were assigned to each arm. At this point, only those receiving oral tenofovir/FTC or oral placebo will continue as planned. The trial is expected to be completed by mid-2012, with final results available by early 2013.

Comment: In the past 18 months, HIV prevention research has yielded both tremendously exciting results and extremely disappointing ones, and this news from the VOICE trial is clearly in the latter category. Not only was the trial intended to clarify the comparative effectiveness of oral versus vaginal-gel strategies for HIV prevention in women, but it was also intended to be the second study required by regulatory bodies for approval of tenofovir gel — assuming the results of the CAPRISA 004 study could be replicated or improved upon. The negative results of the VOICE trial confirm the complexity of using medication-based HIV prevention strategies. Of note, the CAPRISA 004 study used a coitus-dependent dosing regimen (12 hours prior and 12 hours after intercourse), whereas VOICE used daily dosing. If an analogy can be made to the iPrEx trial (and it remains to be seen if such analogy is appropriate), it’s that participants in HIV prevention studies seem to adhere poorly to daily dosing and thus potentially leave some episodes of intercourse “uncovered” by protective antiretrovirals. Details on adherence levels, drug levels in vaginal tissues, and risk behaviors are critical for understanding the vastly different results of VOICE and CAPRISA 004 — and also the conflicting results of various tenofovir/FTC trials in women (Partners PrEP, TDF2, and FEM-PrEP). Until the detailed results of all these trials are fully presented, it is virtually impossible to proceed with much-needed implementation research and demonstration projects in female populations.

Source: Journal Watch HIV/AIDS Clinical Care