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Posts Tagged ‘Microbicides’

Here at the Microbicides 2010 conference in Pittsburgh I got a chance to talk with Dr. Gita Ramjee, one of the top researchers in the field, about the most exciting scientific challenges being discussed at the meeting.  Dr Ramjee is the Director of the HIV Prevention Research Unit at the South African Medical Research Council.  She also explains in the interview why development of an effective microbicide for rectal use is so crucial, for both men and women in Africa, in particular given higher than expected rates of reported anal sex in several countries, as well as in many other regions of the world including the United States.

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This post is by the Global Center’s David Bryden, who is attending the 2010 International Microbicides Conference this week in Pittsburgh. Stay tuned for more coverage of this important conference.

Dr. Sharon Hillier, of the University of Pittsburgh, expressed great hope about the impact of microbicides

An exciting conference on microbicides for HIV prevention has gotten underway in Pittsburgh, Penn. There is an air of anticipation at the meeting because some of the most promising clinical trials of microbicides are due to report results soon, such as the CAPRISA study with findings expected on July 21 in at the AIDS conference in Vienna.  If this study demonstrates a high degree of effectiveness, it will make headlines around the world and could reshape global health advocacy.

A key theme of the conference, appropriately enough for Pennsylvania’s “City of Bridges,” is achieving faster results by building strong connections between scientific disciplines and affected communities, so that studies of these products — such as vaginal or rectal gels, vaginal rings and other methods to prevent infection — can be even more successful.  The 1,000 people in attendance, from 47 countries, have the beautiful view from the balcony of the conference center of the bridges across the river here to remind them of this theme.

At the opening ceremony, Dr. Sharon Hillier, of the University of Pittsburgh, compared the development of microbicides to the successful development of the polio vaccine by Dr. Jonas Salk, right here in Pittsburgh.  That required the use of 200,000 lay volunteers who helped out at trial sites, plus the involvement of 60,000 health care personnel and 64,000 teachers.  She said that microbicide researchers should take inspiration from the polio effort, in particular from its determination, focus, and use of community support.  “We will get there!” she said.  “We will eradicate HIV, and what a beautiful dream that will be.”

Dr. Ian McGowan, of the University of Pittsburgh, stressed that the latest figures on the rate of infection demonstrate the urgency of developing new prevention methods.  He said young African-American men in Baltimore face an annual HIV incidence rate of 10%.  He also said that the needs of men who have sex with men (MSM) are at the forefront, given the deplorable court verdict in Malawi condemning a gay couple to 14 years of hard labor.  MSM in Senegal and Ghana face an HIV incidence rate of over 20% and in Nigeria and Kenya of over 10%. 

Nono Eland, of the Treatment Action Campaign (TAC), noted that both science and activism are essential to HIV eradication

Sunday’s opening plenary brought together scientific and community perspectives.  Nono Eland of the Treatment Action Campaign (TAC) took off her outfit to reveal a soccer jersey in recognition of the upcoming World Cup in her home country of South Africa, and she said that a microbicide would be like a good goalie who prevents the ball from getting into the soccer net. She said TAC consistently campaigns for prevention as it mobilizes for treatment, and she expressed concern that funding cuts in the fight against AIDS will threaten prevention. 

She said that community awareness of the importance of microbicide research is still far too low.  She recounted a meeting she attended of the gender committee of a major union in South Africa where people where clearly not aware of the research underway there.  A major problem she said is that people are skeptical that innovations would ever reach them.  She recounted one woman asking her about the AIDS vaccine, saying “I do not have access to the HPV vaccine, which already exists, so how would I ever gain access to an AIDS vaccine?” 

Eland also emphasized the need for a strong partnership with advocates to get innovations to the field, and she said “science without activism can only go so far.”

Dr. Robin Shattock of the University of London said it was concerning that there were only three microbicide trials underway. He said there was still insufficient lobbying for support for this research.  The lack of funding has forced researchers to prioritize, considering potency, selectivity, potential for combination (e.g. with contraceptives), and stage of development. He sketched out some of the questions facing researchers, such as how much of the microbicide is needed, exactly where in the body and how to maximize continued, proper use of the product (i.e., adherence).

 Check back here at this blog for more reports from the meeting! You can also find more info at the conference website here: http://www.microbicides2010.org/

 

 

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If there’s any question about the value of U.S. investments in scientific research on HIV/AIDS, Anthony Fauci probably put it to rest today by noting that in the period since HIV first emerged, “we went from a 26-week lifespan to a 40-year-plus life span” for those infected with the virus. Talk about measureable outcomes.

That dramatic change—from death sentence to chronic manageable disease—is thanks, in large part, to the 30-plus antiretroviral drugs developed through scientific inquiry over the last three decades. Fauci’s remarks came at congressional briefing today, entitled “AIDS Research at NIH: New Opportunities to Change the Course of the Epidemic,” sponsored by the HIV Medicine Association, IDSA’s Center for Global Health Policy, and several other groups.

Fauci, director of the NIH’s National Institute of Allergy and Infectious Diseases, and other presenters, including two IDSA physician-scientist experts, spoke of the vital need to maintain and increase U.S. support to combat the HIV/AIDS epidemic, whether through an eventual vaccine or biomedical and behavioral prevention strategies.

There is a presumption in some quarters, Fauci said, “that we really have our arms around this and things are stable.”  But with 2.7 million new infections each year, the epidemic is still spiraling.

“In the U.S.,” Fauci added, “yes, things are stable, but they are stable at a completely unacceptable level.” There are about 1.1 million people living with HIV in the U.S., with 56,300 new infections each year–a number that has stayed intractably level for the last decade.

Right now, “we are not winning the game,” Fauci said, which means it is imperative to continue the search for a cure.

“Some have thought this is an impossible goal,” he said. But while there have been many disappointments in the vaccine arena, Fauci said there is great hope of a “functional cure,” in which HIV patients are treated aggressively and early enough that they  go into permanent remission and no longer requirement ARV therapy.

“This is eminently feasible,” he said, describing novel prevention approaches now under study, including microbicides and “test and treat” strategies.

Dr. Wafaa El-Sadr, director of Columbia University’s International Center for AIDS Care and Treatment Programs, said that with ARVs, an estimated 3 million lives have been saved.

“I call that success,” she said. But noting there’s still much “unfinished business,” she said, “we should be energized to continue this work” both in expanding access to treatment, finding new drugs, and researching new prevention tools.

She noted that in parts of the U.S., including D.C., the prevalence of HIV surpasses the rates in some African populations, but that here, it is a very localized epidemic, with African Americans disproportionate impacted. That requires distinct approaches to treatment and prevention.

“We have to reconceptualize our approach to the epidemic,” she said, and look for more structural, socio-economic interventions. But to do that, and be successful, requires more research. She pointed to a study she’s involved with that is trying to identify the risk factors for HIV among women. Once the study gives them some answers, she said, they will need to do another study to figure out what interventions work to mitigate those risk factors.

Dr. El-Sadr also described the “test and link-to-care” study underway in Washington, D.C., and the Bronx, which will look at whether it’s possible to significantly reduce transmission with such an approach.

“This is the epitome of a complex study,” she said, “but it’s the future of what HIV prevention will look like.”

“… We have an emergency in this country and an emergency around the world,” she concluded.  “There’s a need to continue an ambitious, innovative, courageous research agenda.”

Dr. Adaora Adimora, a professor of medicine and epidemiologist at the University of North Carolina, took the audience in a different direction, with a talk about why it is vitally important to cultivate and support minority researchers in this field.

She joked that the subtitle of her presentation should have been: “Why can’t white men solve all our problems?” But  Dr. Adimora quickly turned serious in noting that HIV disproportionately affects minorities, particularly those who are disadvantaged and therefore  vulnerable to forces that put them in the path of the virus.

“Minority investigators bring a unique perspective” on the health issues that affect their community, and are likely to think of research questions and connections that other researchers do not.

For example, until the early 1990s, the HIV-STD field focused research questions on “numbers of parents and sexual behaviors,” she said. “Poverty was recognized as a risk factor but it wasn’t clear how being poor could get you an STD, including HIV. Through the efforts of researchers, many of whom are minorities, this view broadened to include the importance of social forces and the pathways that link these social forces to HIV and other STDs.”

And understanding these pathways is critical to developing successful interventions, she added.

Lack of funding is the main reason that minority researchers leave the field, she said, noting that an early NIH grant was the key to her own successful career in research.

“It’s unlikely my career would have survived” if not for that grant because, she said, she would have had to devote all her time to seeing patients. “An increase in grant funding is critical to ensure that more talented investigators of all races and ethnicities are not lost,” she said.

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Willard Cates, Jr., MD, MPH, President, Research, Family Health International, recently gave a provocative presentation at a Microbicides Trial Network meeting in Washington, D.C., providing insights about the potential public health impact of microbicides, if the scientific evidence demonstrates efficacy in preventing HIV transmission. We spoke with Dr. Cates about the challenges of translating scientific data into real-world prevention gains.

 Q: There’s a lot of excitement among AIDS experts and advocates about Pre-Exposure Prophylaxis (PrEP) to prevent HIV transmission. The main question in the advocacy community tends to be: Will we have enough resources for PrEP roll out if and when the scientific evidence shows efficacy? But your presentation suggests that our collective expectations for the public health impact of PrEP may be overblown. Is that an accurate summary or how would you characterize your bottom-line message here?

A: The bottom line is yes, that is right. We need realize that the primary place we have focused as HIV prevention scientists has been at the innovation stage–will the prevention product work or not? We haven’t gathered a lot of evidence about how things will get ramped up if effective. We’ve made many assumptions and done some creative thinking, but we haven’t generated the qualitative or quantitative data about how people would be using oral PrEP or topical microbicides in the real world. Our discussions have been largely theoretical.

Q: You use the term “prevention cascade” in the presentation, which gets at this disconnect between scientific efficacy and real-world practical impact. Can you walk us through what that prevention cascade is and what the implications are?

A: With PrEP, a simple prevention cascade model looks like this: If you have no product at all, in an HIV discordant couple, let’s assume 10 infections will occur for every 100 women exposed to HIV. If you have a PrEP product that’s 50 percent effective, you will still get 9 infections for every 100 women exposed, because only about half of those women will have access to the product, and only half of those 50 will actually use it. Even with a PrEP product that’s 80 percent effective, you still get 8 infections, because of the access and adherence barriers.

Moreover, our information in the PrEP studies is being gathered in a clinical trial setting that’s as close to perfect use and perfect access as we can expect. The participants come back to get evaluated monthly, they get regular reminders about what to do, they get a regular stock of product every month. They are supported to an extent that doesn’t exist outside this research setting. In the real world, they’re going to have to pay for the product, travel to obtain it, have it be in stock, and so on. Unfortunately reality means imperfect access and imperfect adherence.

Once you have adjusted for the prevention cascade—meaning the number of people who drop out because of adherence or access issues—the effect of PrEP or microbicides only gains us a few averted infections for every 100 exposures. What would gain us a lot more public health impact is if we were able to increase access and increase adherence.

Yet we spend all this effort and money in trials trying to get from 50 percent to 80 percent effectiveness with PrEP or microbicides.  We’re nibbling around the edges of public health impact, trying to get incremental improvements in the tools. But the number of infections prevented by any of our innovations is much more affected by access–Can the community get this prevention product? Do they use this product?–than by any marginal increase in product effectiveness.

Q: You gave a startling example of this with prevention of mother-to-child transmission (PMTCT) scale-up. It showed that with no PMTCT services at all, you get 25 HIV-infected babies for every 100 HIV-positive pregnant women. With access to highly active antiretroviral therapy (HAART), you still get 17 HIV-infected babies. Can you walk me through that–it just seems so hard to believe that you still have so many new infections with full scale-up of the most potent intervention we have.  

A: Lynne Mofenson of NIH has presented these PMTCT extrapolations in many settings. She estimates only 92 percent of women will come to the clinic in the first place. Of those, 75 percent will get tested for HIV, and of those, only 50 percent will get ARVs.  Using these access/adherence measures, she shows the difference in infections averted between single-dose nevirapine and triple-drug HAART is only two infections.

Where we are really going to get bang for the buck is by increasing those who will take up the particular intervention by going to the antenatal clinics, getting tested, and taking ARVs. Let’s say, for example, we were able to increase by 50 percent the number of women who come to a clinic for antenatal care, and then increase by 50 percent the number who get tested once there, and increase by another 50 percent those who take the ARVs if they test positive, then you’d see much greater public health gains, compared to making similar improvements with the drug regimens.

As public health people, we need to do a better job of bringing our scientific creativity to the whole field of program science. We want to increase in the real-world access to the product and improve the circumstances under which people use these prevention tools. Once we have an effective product, whether it’s condoms, PrEP, or microbicides, we need to optimize our public health bang by having that product accessed and used. This seems platitudinous, but we get so focused on the trials to show effectiveness, we neglect the factors most associated with having public health impact.

Q: So what would that mean in terms of crafting a more effective PMTCT program?

A: At the same time we’re looking at the molecular level approaches to new drug regimens, we need to think about and invest in creative approaches that will overcome some of the barriers to access and adherence. For example, we could look at providing simple ARV regimens to all pregnant women, rather than just to those who get tested and are infected. We need to look at what are the gains and risks perhaps of using such broader scale approaches. This is a new time program science.

Q: And what might that mean for PrEP roll out?

A: Now is the time to think beyond our trials. How are we really going to use a successful product? If oral PrEP is successful, who would get it? And if topical microbicides are successful, who would get them?

I used to think because the orals are so much easier to use than topicals, they would have wider application. But because of cost and resistance issues, with the possibility of intermittent use and people sharing, I now think that oral PrEP, if successful, should only focus on the highest transmission intervals and individuals–discordant couples trying to get pregnant, transient sex workers, etc.

For topicals, I’ve also gone through an evolution. Because we’re not giving it systemically, topicals are not absorbed to same level as oral medicines. We believe we’ll have fewer resistance and safety concerns. Surprisingly, topicals may even have adherence advantages. One thing we’ve found is when these trials are over, many of the women do not want to give back the product. They like the product. It gave them a power over their sexual activity, and apparently it increased their pleasure. So another approach to improving adherence is finding out what aspects of the topical microbicides made women not want to give it back at the end of trials. We can then build on those motivations as a way to ramp up the topicals.

Q: So knowing what you know now, if you were in charge of U.S. government funding for HIV prevention, what would your priorities be and why?

A: I would allocate an increasing amount of prevention resources to examining creative systems to increase the access and adherence.  We need to anticipate, if the products are effective, how we can get them to scale more quickly. We should start funding science that will address those questions now, so the evidence will guide our ability to have a faster public health impact.

The Administration is already moving in this direction. PEPFAR’s initial aim was to get treatment out quickly to those most in need. Now the emphasis is getting it out more efficiently and effectively in a way that’s going to have a public health impact, including using ART for prevention.

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The National Institutes of Health is seeking grant applications for its Microbicide Innovation Program.  The agency is looking for projects that will advance the development of new microbicides or shed new light on the characterization of microbicides for use against HIV or STIs linked to HIV, among other scientific pursuits.

 

Here’s the link for more info:

 

http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-09-021.html

 

 

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