Faculty Bibliography

While the long-term goal is to develop highly effective AIDS vaccines, first generation vaccines may be only partially effective. Other HIV prevention modalities such as preexposure prophylaxis with antiretrovirals (PrEP) may have limited efficacy as well. The combined administration of vaccine and PrEP (VAXPREP), however, may have a synergistic effect leading to an overall benefit that is greater than the sum of the individual effects. We propose two test-of-concept trial designs for an AIDS vaccine plus oral or topical ARV. In one design, evidence that PrEP reduces the risk of HIV acquisition is assumed to justify offering it to all participants. A two-arm study comparing PrEP alone to VAXPREP is proposed in which 30 to 60 incident infections are observed to assess the additional benefit of vaccination on risk of infection and setpoint viral load. The demonstrated superiority of VAXPREP does not imply vaccine alone is efficacious. Similarly, the lack of superiority does not imply vaccine alone is ineffective, as antagonism could exist between vaccine and PrEP. In the other design, PrEP is assumed not to be in general use. A 2 x 2 factorial design is proposed in which high-risk individuals are randomized to one of four arms: placebo vaccine given with placebo PrEP, placebo vaccine given with PrEP, vaccine given with placebo PrEP, or VAXPREP. Between 60 and 210 infections are required to detect a benefit of vaccination with or without PrEP on risk of HIV acquisition or setpoint viral load, with fewer infections needed when synergy is present

On 13 June, donors to the GAVI Alliance will gather in London to affirm their commitment to fund immunizations in the developing world. At the meeting, participants will address the estimated $3.7 billion financing gap needed over the next four years to scale up childhood vaccination efforts to meet the demand forecasts for those countries that receive assistance from the Geneva-based organization. But attendees of the pledging conference will also be discussing something not on the formal agenda: the announcement last month that Seth Berkley, who founded and heads the International AIDS Vaccine Initiative (IAVI), will take over the helm of the alliance in August. Berkley will lead a unique chapter in GAVI's development as the organization narrows in on the looming deadline set by Millennium Development Goal 4, which aims to reduce child mortality by two thirds by 2015. Yet, in a sense, these efforts will be a continuation of the work Berkley has fostered at IAVI since he formally launched the New York-based nonprofit in 1996. Berkley, an epidemiologist who previously held jobs with the Rockefeller Foundation, the Carter Center and the US Centers for Disease Control and Prevention, has witnessed ups and downs in the vaccination field, from the disappointing STEP trial in 2007 to the more recent good news from the 2009 Thai study, which reported as much as 31% protection against HIV. Roxanne Khamsi spoke with Berkley about what he has learned in his quest for a preventative shot against AIDS.