The Past, Present, and Future of HIV Microbicide Research Advocacy

Polly Harrison founded and led the Alliance for Microbicide Development (http://www.microbicide.org) from 1998 to early 2010. She is now a senior policy advisor at AVAC. TAG worked closely with Polly in support of microbicide research and in fall 2010 TAGline interviewed her to seek her wisdom and vision for the future.

TAGline: What were things like when you founded AMD?

Polly Harrison: Fairly bleak, which was why the Alliance was founded in the first place. The idea came from Mahmoud Fathalla at the Rockefeller Foundation, who provided a seed grant to form a coalition of scientists, biopharmaceutical companies, and advocates to be a “catalyst” at a time when progress toward microbicides was slow, fragmented, and woefully underfunded. There were just 20 of us at the first Alliance meeting in March 1998 but in a year we had almost 100 active participants, a database and regular reporting activities, and busy with constituency building, outreach, media work, and funding analysis. We had two staff and little money, but there was such engagement and enthusiasm that we got tons done in those early years and began to attract more funding. It’s been said the Alliance “made the microbicide field” and there’s truth there. People were attracted by the fact that the Alliance was a neutral convener, educator, and problem-solver. The neutrality aspect caused us problems later but it’s what many value and recall, rather wistfully since the Alliance no longer exists.

You asked when the “HIV microbicide” idea was first suggested. As early as 1987, the National Institute of Child Health and Development was supporting work on “contraceptive microbicides.” Then in 1990 came a hugely influential article by South African epidemiologist Zena Stein that called for “HIV prevention methods that women could use.” Zena argued that absent male concurrence with condom use, women had no way of protecting themselves from HIV infection, and that AIDS was becoming a women’s as well as a man’s disease, not a popular concept at the time.

The Alliance didn’t arise in a total wasteland. Microbicides were in the portfolios of the NIH, Population Council, and International Working Group on Microbicides, in U.S. legislative language and the International Conference on Population and Development Plan of Action, and at the 1996 Vancouver International AIDS Conference, there was the first public announcement of U.S. funding for microbicide research. Still, no one had any real money, the broader HIV advocacy community was focused on therapy and later on vaccines, and the idea of something topical that could help with women’s special risk was seen as scientifically and practically improbable. The failure of the UNAIDS-funded COL-1492 trial announced at the 2000 International AIDS Conference in Durban [South Africa] didn’t help! COL- 1492 was a commercial product based on nonoxynol-9, which was the active ingredient in topical spermicides and also showed activity against sexually-transmitted infections. However, the trial found that COL-1492 not only didn’t protect against HIV infection, but might increase that risk. We were stunned by the results, didn’t know how to handle them, and for a field just getting itself organized, they were traumatic and have had a long half-life.

TL: How have things changed since then?

PH: A lot. Getting an advocacy movement organized and ramped up was vital. Microbicides acquired a public “personality” and some understanding of what they were and might do, and we mobilized constituencies that got successive versions of a Microbicide Development Act introduced in three sessions of the U.S. Congress. None passed but all got introduced with a lot of education, publicity and new allies, and leveraged establishment of a Microbicide Branch [at the NIAID Division of AIDS, NIH] and a dedicated position for microbicides in the Office of AIDS Research. We helped establish the International Partnership for Microbicides and pushed steady increases in microbicide funding so NIH attracted more scientists, USAID raised its investment levels, and more developers advanced more concepts.

TL: What do you think are the leading questions facing microbicide research today?

PH: If you mean challenges to advancing toward a safe and effective product with reasonable likelihood of user adherence, I’d say:

• Funding. But not just more money. I mean funding that follows and supports some kind of rational strategy and consensus among the donors about what makes sense.
• A distinctive collective voice speaking persistently for the special value of topical microbicides for the world’s women.

Those women still don’t have the kind of protection from HIV infection that they need, which is why we set out to develop microbicides in the first place!

If you mean scientific questions, then I’d say we still don’t have:

• Clear understanding of what kind of product will have enough potency for sufficient time to interrupt HIV transmission at key points in that process in ways that are safe for regular use.
• Even one validated biomarker that can give us more assurance of product use and effectiveness than even the best adherence measures we have now.
• A clear view of how any such product and ways to deliver it will best fit the lives of individuals and couples so they feel safer and make their own decisions about that safety.

TL: Do you think research on microbicides has enough political support? Enough research support? Enough commitment to do the research necessary to operationalize microbicides when we have evidence they work?

PH: Short answer: probably not. Let me take each of your questions individually.

Political support: We managed to develop a lot of political attention that, while we never got actual legislation passed, leveraged the supportive NIH responses I mentioned earlier. I don’t think microbicides command that same level of political support now for several reasons:

• The image of a “movement” advocating explicitly for microbicides for women has become blurred. I still believe that women should have their own special “technological identity” because their needs are special. Yes, PrEP [preexposure prophylaxis] and a vaccine would be good for both men and women, but the former has some big challenges and the latter is some years away.
• The economic environment affects microbicides as it does everyone everywhere. We can’t complain since almost everyone is suffering, but we need to be especially careful and attentive because of it. Our “asks” have to be well considered, clear, and strategic. In that connection…
• The economy and the changed political orientation in the U.S. Congress will have impact on support for HIV across the board. What kind of impact? Enough political support? Who knows. Money is already the central issue and we haven’t even gotten to competing health priorities and ideology!

Research support: The economic environment obviously affects funders, who are overwhelmed, confused, and less well-resourced. In the case of microbicides, many donors lack the internal resources or standardized access to true peer review processes to make decisions, so that each donor is vulnerable to the pleadings of individual groups and their own inabilities to assess those.

Commitment: I wish I knew. Some donors clearly remain committed, but some are pressured by economic realities and multiplying demands. Others can’t deal with the realities of scientific and pharmaceutical research, even though such research is well known to be erratic, inconclusive, sometimes just plain disappointing, before success is ever reached—if ever.

TL: What are the lessons learned from the unsuccessful microbicide trials?

PH: Like HIV vaccines, we know what we won’t do again, and more about what we don’t know. Did we move too fast into the clinic with not enough data? No and yes. In some cases, we didn’t have the tools to know what we didn’t know and couldn’t answer without more human data. In others, we thought we knew more than we did, there was a sense of urgency—that, frankly, has not gone away—and we should have asked more questions sooner. As for the scientific questions, there’s been much probing of those lessons by independent researchers and analysts. What we haven’t done is pull those lessons together into a coherent statement to the scientific world. We do know that we won’t invest in microbicide candidates that can’t balance safety and efficacy in the lab—i.e., no more surfactants, no more polyanions.

TL: What are the lessons learned from the successful TDF 5% gel trial3?

PH: Many! The biggest and best is that the concept of a topically applied microbicide is feasible and merits pursuit. We learned that women will use such a product, their partners mostly don’t seem to mind, and that women who use it most benefit the most. We also learned what we don’t know: most importantly, how such a product will be used in “real life”; whether partners will continue to “not mind”; and what frequency of use will provide the necessary level of protection. And for me, one of the most important lessons was the finding that tenofovir was 51% effective in preventing genital herpes infections, and follow-on trials will be exploring that very important fact further.

TL: Are you satisfied by world reaction to CAPRISA-0044?

PH: I’m thrilled! Now we can say that topical microbicides have an accepted identity as an HIV prevention technology worth pursuing. We’ve had some long dark years sprinkled with disappointment, some loss of faith and, frankly, some disdain. To see the joy and hope in so many quarters is beyond gratifying. Not every quarter, which is distressing, but most.

TL: What plans are underway to validate that result?

PH: There are multiple plans and that’s a problem. There are earnest efforts to coordinate and find consensus about what should happen next, but those are confounded by understandable vested interests, funding constraints; and maybe a bit of human cussedness. I feel better since the stakeholders meeting USAID convened a few weeks ago, where a deadline was laid down for producing a road map and timeline for next steps. There is progress in taking some regulatory steps and bridging trials are being designed. But there’s no agreement about which trials will be needed to confirm the CAPRISA-004 results and by whom. Even the best road map will have to be accepted by all the key players—and there’s the rub.

TL: Where is the field going, and where does it need to go?

PH: We obviously have to finish what we started with tenofovir, including the VOICE trials and any other trials that are seen as necessary, and we have to be sure that the work on the dapivirine ring goes forward as the science indicates. To do all that will require major investment and we have to assure that ahead of time so that we don’t have any damaging interruptions. At the same time, we can’t forget the rest of the pipeline. There are roughly 70 candidate microbicides of various sorts in the preclinical pipeline and there has to be a strategy for weeding those out and supporting and moving plausible survivors. I want to see work proceed with combination products that hit HIV at various points in its nasty trajectory or can prevent more than one sexually transmitted infection or combine such prevention with contraception. There isn’t a pharmaceutical company on the planet that would ignore its earlier pipeline just because there were likely candidates in late-phase research, or ignore improving those candidates, and I’m worried that funding constraints will have that effect. The NIH plays the biggest role in the early science and we have to be sure that there’s enough support there for that. If not, other funders are painfully few. We all have to worry about that.

TL: What are you, as an experienced microbicide advocate, planning to do now that the AMD has closed?

PH: I am really gratified to have been able to take on the role as senior advisor to AVAC. That has been useful to us both. I’ve been able to assure the appropriate transfer of the intellectual property that the Alliance developed over the years and to also serve as a symbol that the validity of the microbicide concept remains alive. I still seem to have a useful voice and as long as anyone listens to me, I probably will keep on talking. And there’s plenty I want to write!

TL: Are there lessons for advocacy?

PH: Many. The most powerful one surprised me. The microbicide movement was most effective when we had few financial resources but many committed hearts and minds, even when the political and socio-cultural environment was not welcoming. Resource imbalances and trial failures have hurt that movement and we have not regrouped as a dedicated constituency. Some think the field has matured to the point where specific microbicide advocacy is no longer required. I disagree; much organized conversation and advocacy remain essential. The final lessons for advocacy for microbicides and women’s particular needs have not yet been told but I’m uneasy. Ask me again next year.

TL: Do you have any other reflections you’d like to share?

PH: Just one. In the earliest days, our circle of true friends beyond the microbicide community was small. TAG was very early among those true friends. That hasn’t changed and we’re so grateful.

Read more about Polly Harrison here.