Preparing for the unexpected: the pivotal role of social and behavioral sciences in trials of biomedical HIV prevention interventions.

A range of efficacies have been reported for biomedical HIV prevention interventions, including antiretroviral treatment, male circumcision, preexposure prophylaxis, microbicides, and preventive vaccines. This range of efficacies probably results from the influence of multiple inputs and processes during trials, including the strength and target of the intervention, host factors, target population characteristics, level of HIV exposure, and intervention dose. Expertise in social and behavioral sciences, in conjunction with basic science, clinical research, epidemiology, biostatistics, and community, is needed to understand the influence of these inputs and processes on intervention efficacy, improve trial design and implementation, and enable interpretation of trial results. In particular, social and behavioral sciences provide the means for investigating and identifying populations suitable for recruitment into and retention in trials and for developing and improving measures of HIV exposure and intervention dose, all within the larger sociocultural context. Integration of social and behavioral sciences early in idea generation and study design is imperative for the successful conduct of biomedical trials and for ensuring optimal data collection approaches necessary for the interpretation of findings, particularly in cases of unexpected results.

High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects.

BACKGROUND: In clinical trials, canarypox ALVAC-human immunodeficiency virus (HIV) vaccines have been shown to elicit human HIV-specific cytotoxic T lymphocyte (CTL) responses in some but not all healthy uninfected adults.Methods. A clinical trial was conducted to examine whether the vaccine vCP1452 would elicit a greater HIV-specific CTL response when given at a dose of 10(8.0) TCID50 (60 participants) than when given at the regular dose, 10(7.26) TCID50 (40 participants); as a control, a placebo vaccine preparation also was administered (10 participants). RESULTS: Two weeks after the last vaccination in a series, HIV-specific CTL responses were not significantly different when measured by either chromium-release assay (8% and 16% in the high- and regular-dose recipients, respectively) or interferon- gamma ELISpot assay (8% and 15% in the high- and regular-dose recipients, respectively); moreover, recipients of the higher dose had greater local and systemic reactions (P<.001). CONCLUSIONS: High reactogenicity associated with an increased dose of vCP1452 negates the need for further evaluation of this strategy to boost the frequency of HIV-specific CTL response in seronegative human subjects. Development of highly immunogenic canarypox vectors requires further work to optimize vector and insert design, as well as novel ways to increase dosage and to reduce reactogenicity.