Hunting For Correlates

Even when biomedical interventions against HIV work in clinical trials, as they have lately for several HIV prevention strategies, scientists don’t always know why. To borrow an analogy from the breathtaking backdrop of the annual Keystone conference this week, identifying the correlates of immune protection is a Nordic slog through the wilderness, not an Alpine run.

Researchers still can't explain the results of the prime-boost vaccine regimen tested in the RV144 trial that showed an efficacy as high as 60% (based on the modified intent-to-treat analysis), but that slowly waned over the course of the three-and-a-half-year trial to a modest 31%. And efforts to better define the correlates of protection may be stymied by the relatively sparse supply of samples that were collected over the course of the huge trial of 16,000 participants, and the limitations of the immunological assays that are typically used.

During the closing presentation at today's correlates session, Juliana McElrath, a professor of medicine at the University of Washington, said the number of relevant assays under consideration for a correlates analysis of samples from the RV144 trial has been “broadened dramatically,” from four to 15, including assays that measure B cell and antibody responses, innate responses, T-cell responses, and mucosal responses. 

The assays will be used in a case-control study of 51 HIV-infected volunteers who received the vaccine and a larger control group of uninfected vaccinated individuals to measure the quantity and breadth of immune responses. Researchers, who are still reviewing the options, will be choosing 4-5 primary assays, and a larger number of exploratory assays for the case-control study.