July 21, 2009
In this summary, Ronald Gray, M.D., discusses his plenary update on "Biomedical Prevention, Including Microbicides, Vaccines, Circumcision and PrEP." To view his full presentation, click here. To review his slides, click here.
Ronald Gray: I've been asked to discuss 20 years experience with clinical trials via medical prevention of HIV infection1 and it's been a very sobering experience.
There were 29 completed [biomedical prevention] trials, only four of which showed any efficacy for reduction of HIV and three of those were trials on male circumcision.
Then we reviewed 11 trials on microbicides, none of which showed efficacy for HIV prevention in an intention-to-treat analysis. One microbicide called PRO 2000 did suggest the possibility of about a 30% reduction in HIV.9
HIV vaccine trials, as you well know, have been negative. And there is evidence of one vaccine (the MRK adeno 5 vaccine) that may have increased risk, particularly in men who had prior immunity to the adeno 5 vector, and who were uncircumcised.
The circumcision story is a little better. There are three trials that have shown that circumcision protects men from HIV, and more recently shown that it protects men from herpes and from human papillomavirus [HPV].
Last week we just published a trial in which we circumcised HIV-infected men to determine whether we could reduce transmission to their initially uninfected female partners.10 Sadly, we did not see protection of the women in the short term. But there are prior studies -- some that we've conducted, and one that we presented at this meeting -- that suggest that men who are circumcised in childhood may have a reduced likelihood of transmitting to their wives.
Craig McClure: Ron, question for you. During your talk, you postulated on why it may be that there are so many negative results recently from a number of biomedical prevention trials, STIs and others. One factor you brought up was the fact that possibly the incremental impact of that intervention may have been so small that the trials weren't powered to pick it up. So given the number of interventions there are now for HIV prevention -- including antiretroviral therapy and the potential next year and the year after if we have positive results of the pre-exposure prophylaxis [PrEP] trials with antiretroviral therapy for HIV-negative people -- what is the future for biomedical prevention trials? And how can some of these challenges you identified be addressed so that we can get the answers that we all so desperately want from these trials in the future?
Ronald Gray: Thank you. That's an impossible question. [Laughs.] I think there are several things. Obviously, we hope that pre-exposure prophylaxis trials are successful. But I think the lesson we have to learn from the trials that have been completed is that we need to do much more fundamental research on immunologic mechanisms to further development of vaccines and potentially of microbicides. I would argue that some of that focus should shift from the effort to develop systemic immunity to working with much more causal barriers, causal immunity, so we can prevent the virus from entering the body. I do believe that that area of research -- though in its early stages -- could ultimately provide new innovative prevention methods.
This transcript has been lightly edited for clarity.
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