Translating clinical efficacy into public health effectiveness

At the recently concluded XIX International AIDS Conference (AIDS 2012), not only the decibels went up on ending AIDS but also sane voices were heard demanding a well-costed and thought-through strategy on how to end AIDS. One of the strategies that will complement a comprehensive HIV prevention, treatment, care and support plan to end AIDS is preventing HIV transmission. In this context, we need to look beyond the Phase III trials in HIV prevention research so that if the product being tested is proved to be effective, we have the means and well-thought plan to make it available for those people in need, without delay. 

The HIV prevention research is certainly going ahead with rectal microbicides phase II efficacy clinical trials (MTN017) about to begin in four countries (US, Thailand, South Africa and Peru), US FDA's approval to use 'Truvada' as pre-exposure prophylaxis (PrEP) for HIV prevention, vaginal microbicides research and HIV vaccine science progressing ahead, treatment as prevention (TasP) getting a buy-in as never before, among other positive developments that give us hope.

TRANSLATING CLINICAL EFFICACY INTO PUBLIC HEALTH EFFECTIVENESS
"We need a plan that the day efficacy trial is over participants should continue to have access to the products. We have spent a lot of time talking about how difficult rolling out PrEP is going to be, we don’t yet have fully funded demonstration projects to tell us how to translate clinical efficacy into public health effectiveness. I want to make sure that when we do get a result of phase III rectal microbicides study we do know what to do then and have resources to do it" rightly said Mitchell Warren, Executive Director, AVAC - Global Advocacy for HIV Prevention. 

Mitchell Warren is right on spot. Let us be reminded that US FDA had approved female condoms in 1993. Even 19 years after, and despite being effective in preventing HIV (and other sexually transmitted infections (STIs) and unintended pregnancies), female condoms are yet to be made available in the way they should have, to address unmet needs of women to protect themselves from STIs including HIV, and unintended pregnancy. "Nineteen years after US FDA approved female condoms, we still do not have fully funded, well designed, and well-monitored programmes, because we focus too much on the product, whether it is a female condom, microbicide (rectal or vaginal) or oral PrEP it is not the product, it is the programme that will matter" said Mitchell Warren.

ENSURE EXCITING SCIENCE TRANSITS INTO ACTUAL PRODUCTS AND PROGRAMMES
Added Warren: "We need to make sure that there is a clear strategy that is described scientifically, costed financially" to move the products that have proven effective in preventing HIV in clinical studies into actual products and robust programmes. "It is not just a one year deal, we need to be looking at next 3, 5 or 7 years to seek how exciting science transits into actual products" said Warren.

CAPRISA004 was a phase IIb microbicide trial of 1% tenofovir gel, results of which were the hallmarks at the 2010 International AIDS Conference in Vienna. This trial showed that there were 39 percent fewer infections among women who received 1% tenfovir gel compared to women who received the placebo gel. "CAPRISA004 finished almost two years ago and we still wait for a follow on study" said Warren. Follow on study after CAPRISA004 is going on but what about ensuring access to trial participants of CAPRISA 004 to the gel?

FACTS001 is a follow-on large-scale placebo-controlled study which is currently underway to test the safety and effectiveness of vaginal tenofovir gel used before and after sex to protect women against HIV infection and also against Herpes Simplex Virus (HSV-2: virus that causes genital herpes). FACTS001 study is aimed at confirming and expanding the groundbreaking findings of the CAPRISA 004 tenofovir gel trial. If the FACTS studies confirm that tenofovir gel is effective, these combined data could contribute to the licensure of the first vaginal microbicide product and subsequently provide women with a powerful new women-controlled HIV prevention method.

IS THERE A PLAN POST-LICENSURE?
Is there a plan post-licensure - that is a big question that needs answers and discussions now. Socio-economic, cultural, legal and policy environment, and other factors that are a barrier for many key populations to have access to existing HIV prevention services, need to be addressed now. This will not only possibly increase the utilization of existing services but also prepare our systems well for a better uptake of new technologies (when they become available) as well. 

RECTAL MICROBICIDES: Thinking beyond Phase III trials...
Rectal microbicides advocacy took a sprint with International Rectal Microbicides Advocacy (IRMA) network gaining support around the world. Despite anal sex happening in our countries between men who have sex with men (MSM), transgender people and heterosexual couples, the culture of silence kept the unique prevention needs and contexts less talked about. Thanks to IRMA not only the issue is more talked about but also research for rectal microbicides has gained momentum and growing community engagement.

Dr Ross D Cranston, Protocol Chair, Division of Infectious Diseases, University of Pittsburgh, US said to Citizen News Service (CNS) before AIDS 2012 that "We have just received regulatory approval for MTN017 (phase II trial of rectal microbicides) from the Division of AIDS." MTN017 is an extended safety study (in phase II now). Participants will be randomized either in daily rectal formulation of 1% tenofovir gel or the same gel with associated rectal sex, and third sequence is oral truvada.

Since people who have anal sex often use some kind of lubricant, there is a hope that if rectal microbicides if found effective, are introduced as a lubricant, then the uptake might be more because people already are comfortable in using lubricants for anal sex. Dr Suwat Chariyalertsak, Director, Research Institute for Health Sciences (RIHES), Chiang Mai University, Thailand said: "We had done a small study on lubricant use in transgender people earlier and nearly 95% of study participants reported to use lubricants. Introducing rectal microbicides when found safe and effective for STI/HIV prevention in future might be easier in transgender people because they are already using lubricants and if lubricants have an added ingredient that provides protection against STIs including HIV that will be so good."

But we know very little whether lubricants that are available in market today are safe, unsafe or have no effect in preventing STIs including HIV. The way lubricants are regulated by the governments is not consistent. Marc-Andre LeBlanc, IRMA Secretary, who also leads lube safety initiatives, said: "Regulatory agencies in various countries classify lubes differently - as medical devices or cosmetics, for example. Typically they require no safety data on the rectal use of lubes in humans."

Clearly a lot more planning needs to be done to ensure we are really prepared to take rectal microbicides that come out of clinical trials forward to the communities that need them to protect themselves from STIs including HIV. As Mitchell Warren had said above, we need a robust 'programme' vis-a-vis 'product' to turn the tide...

Dr Ian McGowan, co-principal investigator of the University of Pittsburgh-based Microbicide Trials Network (MTN) said: "I am a firm believer that these drugs (rectal microbicides) in the right amount, at the right place, at the right time, will work."

As goes the old golden adage, 'Those who fail to plan, plan to fail', let's plan really well to make sure that people whose HIV prevention needs are not currently met, are met as soon as possible and we have a robust strategy in place to bridge that gap. We cannot afford to fail or delay any further.