From the laboratory to clinical trials and back again: lessons learned from HIV prevention trials.

Problem: Inadequate, irrelevant, or inappropriate timing of biological specimen collection during clinical trials is a cause for delay in understanding and explaining correlates of protection and/or effectiveness, particularly at the portal of entry in the context of sexual HIV transmission and its prevention.

Methods: We present examples of HIV prevention trials to illustrate the impact of preplanned versus unplanned laboratory science program on the interpretation of trial results and advancement of the field.

Results: Of the five completed pre-exposure prophylaxis trials, only two announced main outcome results simultaneously with data on correlates of drug-related effectiveness. In four of the vaccine trials completed, the only one that showed a protective effect presented data on protection correlates significantly later.

Conclusion: Clinical trials must preplan collaborative immunophysiological research and prioritize biological specimen collection and storage for enhancement of research on correlates of protection. Similarly appropriate specimens should be prioritized for pathogenesis research.