TAG has previously covered Merck's adenovirus-based HIV vaccine candidate and the efficacy trial of this vaccine that began at the end of 2004 (dubbed the STEP study):
At the recent AIDS Vaccine 07 conference in Seattle, researchers from the HIV Vaccine Trials Network (HVTN) presented an update on the trial's status. Enrollment of all 3,000 volunteers was completed in March of this year and data collection and follow up are ongoing. Results should be available by 2009/2010.
Update on the Merck Ad5 phase II trial (the STEP Study-- Merck V520 protocol 023/HVTN 502)
MN Robertson4, D Mehrotra4, D Fitzgerald2, A Duerr3, G O’Neill4, D Lawrence1 and S Buchbinder5
1 DAIDS/NIAID/NIH, Bethesda, MD, USA; 2 GHESKIO, Portau- Prince, Haiti; 3 HVTN, Seattle, WA, USA; 4 Merck Research Laboratories, North Wales, PA, USA; 5 SF Dept of Public Health, San Francisco, CA, USA
Background: Cell mediated immune (CMI) responses may play a key role in the control of HIV. In Phase I studies, the MRKAd5 HIV-1 gag/pol/nef vaccine had an acceptable safety profile and elicited CMI responses in a high proportion of volunteers; therefore, this vaccine has moved forward into a Phase II test-of-concept trial.
Objective: To test the concept that a vaccine capable of eliciting HIV-specific CMI responses could prevent persistent infection and/or delay disease progression.
Methods: Phase II prospective, randomized, multi-center, double-blind, placebo-controlled study of 3000 HIV seronegative volunteers at high risk of acquiring HIV in regions of the world where clade B predominates (N. America, S. America, Australia and the Caribbean). Participants are randomized (1:1) to receive 3 injections of either MRKAd5 HIV-1 gag/pol/ nef or placebo. Randomization is pre stratified by gender, baseline Ad5 titer, and study site. Participants will be tested ~every 6 months for acquisition of HIV. At each visit where HIV testing is performed, participants are questioned about self-reported risk behaviors; risk reduction counseling is provided. If a study participant becomes HIV infected, plasma HIV viral load and CD4 cell counts will be measured frequently. The final analysis will occur when ~100 new infections have occurred subsequent to the 12th week in trial. Safety and efficacy are being monitored by an independent DSMB.
Results: Enrollment began in Dec 2004 and was completed in Mar 2007. Greater than 90% of the participants that have been in the trial for at least 6 months have received all 3 study injections, but follow-up tends to decline thereafter. Study participants are ~38% women and ~68% are non-Caucasian. Thus far, the study vaccine has been generally safe and well tolerated. Based on preliminary, blinded data, the most commonly reported adverse experiences are headache (20.5%), fever (12.5%), fatigue (6.5%), and diarrhea (6.3%). Behavioral data suggests that the study has succeeded in enrolling a high risk population and reported risk behavior does not increase with trial participation.
Conclusion: High risk populations, including high risk women, can be enrolled into vaccine efficacy trials. Retention for long term follow-up visits can be challenging. Accumulating incident infections and lab-clinical outcomes will address whether vaccine-induced HIV-specific CMI responses can prevent persistent infection and/or delay disease progression.