AIDS Conference Changes the Dialogue

Asia Sentinel

Translating clinical efficacy into public health effectiveness

The recently concluded XIX International AIDS Conference in Washington, DC, appears to have gone a considerable distance on changing the dialogue on ending AIDS, with new emphasis on preventing transmission in the first place as one of the strategies that wouldl complement a comprehensive HIV prevention, treatment, care and support plan to end the disease.

In this context, it is necessary to look beyond the current phase of trials in HIV prevention research so that if the product being tested is proved to be effective, the means and well-thought plan to make it available for those people in need can be developed without delay.

HIV prevention research is going ahead with rectal microbicides phase II efficacy clinical trials about to begin in the US, Thailand, South Africa and Peru. Other hopeful developments include the US Food and Drug Administration’s approval of the microbicide Truvada as pre-exposure prophylaxis for HIV prevention, vaginal microbicide research and HIV vaccine science progress and unprecedented emphasis on treatment as prevention.

“We need a plan that the day efficacy trials are over participants, should continue to have access to the products,” said Mitchell Warren, executive director of AVAC – Global Advocacy for HIV Prevention. “We have spent a lot of time talking about how difficult rolling out pre-exposure prophylaxis 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 the results of the phase III rectal microbicides study, we do know what to do then and that we have resources to do it.”

Warren is right. For example, the FDA approved female condoms as early as 1993. Even 19 years after, and despite their effectiveness in preventing HIV as well as other sexually transmitted infections and unintended pregnancies, female condoms are yet to be made available in the way they should have been to address the unmet needs of women to protect themselves.

“Nineteen years after the 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 program that will matter,” Warren continued.

There must be a clear strategy that is described scientifically and costed financially to move the products that have proven effective in preventing HIV in clinical studies into actual products and robust programs, he said.

“It is not just a one-year deal, we need to be looking at the next three, five or seven years to seek how exciting science transits into actual products,” Warren added.

A microbicide trial of 1 percent tenofovir gel, the results of which were the hallmarks at the 2010 International AIDS Conference in Vienna, showed that there were 39 percent fewer infections among women who received the gel compared to women who received a placebo gel in the trial, known as CAPRISA004.

“CAPRISA004 finished almost two years ago and we are still waiting for a follow on study,” Warren said. “A 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 the Herpes Simplex virus. The 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.

Whether there is a plan post-licensure is a big question that needs answers and discussion. 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 must be addressed. This will not only possibly increase the utilization of existing services but also prepare health systems well for a better uptake of new technologies (when they become available) as well.

Rectal microbicides advocacy is gaining support around the world. Although anal sex happens between men who have sex with men, transgender people and heterosexual couples, the culture of silence has kept the unique prevention needs and contexts less talked about. Now not only is the issue 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, said before the AIDS 2012 conference 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 percent 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.

“We had done a small study on lubricant use in transgender people earlier and nearly 95 percent 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,” said Suwat Chariyalertsak, Director, Research Institute for Health Sciences, Chiang Mai University, Thailand.

But we know very little whether lubricants that are available in the 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.

“Regulatory agencies in various countries classify lubes differently – as medical devices or cosmetics, for example,” said Marc-Andre LeBlanc, IRMA Secretary, who also leads lube safety initiatives. “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.”

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