Why Won't AIDS Donors Confirm Their Best New Hope for Avoiding Future Treatment Costs

Celia Dugger must have known she would get a reaction.  She called from South Africa last week with the surprising news that a donor meeting in South Africa had failed to come up with the $100 million necessary to complete the preparatory research on microbicides as an HIV prevention tool for women.  Luckily for me, she considered my spontaneous reaction to be unprintable and persisted until she got a more coherent quote from me, a quote that appears in her succinct and informative New York Times article here.Why so emotional?  I’ve spent the last few months estimating the billions of annual dollars required to keep alive the four-million-and-counting patients whom the US and others are supporting now on AIDS treatment.  And I’ve been projecting the hundreds of billions the US and other donors will have to spend over coming decades to sustain these patients and to expand AIDS treatment access to even a small share of the unmet need for it.  The idea that these SAME donors would balk at a mere $100 million to confirm that microbicides really work is astonishing.Going farther back, a theme of much of my writing on AIDS policy is the need for more donor and government spending on HIV prevention, especially targeted to those most likely to contract and transmit.  However, I have frequently gotten push-back from people who say that

“we’ve tried our best to do effective HIV prevention in Africa and it just doesn’t work.  The only AIDS intervention that demonstrably saves lives is antiretroviral therapy and now that we know that it prevents the treated person from infecting others, that’s the only way forward.”

Even one successful randomized controlled trial (RCT) on male circumcision was not enough to change the mind of prevention skeptics.  And rightly so.  Remember that another highly touted HIV prevention approach, the treatment of curable sexually transmitted infections, first showed promise with a statistically significant benefit in the “Mwanza trial”.  Unfortunately three equally rigorous RCTs, intended only to nail down the magnitude of this benefit, all came up empty.   Not one of the subsequent RCTs of STI treatment was able to show a statistically significant reduction in HIV incidence among those who received the treatment, compared to those who did not.So it was only when two additional trials confirmed that male circumcision confers a large and statistically significant degree of protection that prevention skeptics started to believe that this one HIV prevention intervention might have promise – “but only for men and only if ….”  (There are admittedly lots of context-specific ”ifs”.   Here I discuss the need to continue field evaluation of circumcision as it is rolled out.)Unfortunately male circumcision, even at 50% efficacy, is not enough to stem the need for AIDS treatment in Africa.  And women still need a way to protect themselves, without depending on condom use to which their male partner must consent.  The fact that after years of disappointing negative results, a microbicide gel  has been found to provide almost as much protection to a woman as circumcision provides to a man is extremely exciting news.  (For links to this and other promising prevention results from the Vienna AIDS conference, see the “postcards from Vienna” by Nandini here and me here.)But the results of one microbicide trial, no matter how rigorous, are not enough.  In order to avoid falling into the “Mwanza trial” trap, we need the confirmatory results of at least two other trials, plus additional product development work, before another dependable HIV prevention technique is available for Africa.Like a tractor-trailer headed down a moonlit mountain road, hundreds of billions of dollars of AIDS treatment costs are barreling down towards the donors who are granting the treatment entitlements, especially PEPFAR, the Global Fund and UNITAID.  Effective HIV prevention with male circumcision and now the new female-centered microbicide offer opportunities for donors to step off the pavement, out of the way of this oncoming juggernaut of human suffering and fiscal burden.  Why would they not take advantage of this opportunity by spending the paltry $100 million necessary to confirm the already promising CAPRISA results?While I have no inside information, part of the problem is surely that the donors had too little lead time.  It’s only been a few weeks since the microbicide results were announced and the donors’ current budgets are already committed.  Another part of the answer is that the agencies that are most threatened by burgeoning AIDS treatment costs, by their nature, lack the mandate to fund research, even low-risk confirmatory research such as is needed here.  And donors that do have a research mandate, like the US NIH, the French ANRS and the Gates Foundation, may reasonably find this confirmatory study to be insufficiently risky to qualify as real research.When NIH drug studies reach a similar stage, private industry frequently steps in, investing private dollars in the “development” stage and bringing the product to market.  But gel microbicides for women in poor countries are probably too small a market to motivate the private sector.  Perhaps this is the place for an Advanced Market Commitment (AMC) approach like the one currently being floated for the childhood pneumococcal vaccine.