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What’s Next for PrEP? Part I: Demonstration Projects

, by Reilly O'Neal

This article is the first in a series on the PrEP research agenda. Stay tuned for more about ongoing studies and new trials to identify new drugs for PrEP, examine alternatives to daily dosing, address how well PrEP works for women, and explore PrEP delivery options beyond pills.

PrEP, short for pre-exposure prophylaxis, is a new HIV prevention strategy that involves HIV-negative people taking antiretroviral drugs to avoid infection. Based on studies that showed consistent PrEP users had dramatically lower HIV infection risk—up to 92% in one trial—the drug Truvada (a medication commonly prescribed to treat HIV disease) was approved for use as PrEP in July 2012.

This breakthrough was sorely needed, locally and globally: “In order to take the next step in moving forward to end the epidemic in San Francisco, in the U.S., and certainly worldwide, we need new HIV prevention tools,” remarked San Francisco City Clinic medical director Stephanie Cohen in a presentation February 20 at San Francisco General Hospital. But many questions remain about how best to deliver and use this particular new prevention tool.

That’s where PrEP demonstration projects come in.

Now enrolling in cities across the nation and elsewhere, demonstration projects are working to answer questions about using PrEP outside the carefully controlled setting of a clinical trial. All are gathering data to help inform how PrEP is offered or recommended, where it is made available, and how best to support its users to get the most benefit from it.

Cohen, who is the co-principal investigator of San Francisco’s own PrEP demonstration project, laid out the questions her project and others will address in the coming months and years.

Five Key Questions

Participants in the Demo Project, currently enrolling in at San Francisco City Clinic and in Miami, Florida, are offered free daily Truvada PrEP for up to 12 months, along with regular HIV testing, screening and treatment for other STIs, monitoring for PrEP drug side effects and changes in kidney function, medication adherence and HIV risk-reduction counseling, and free condoms.

Between the free pills, scheduled study visits, and other aspects of participation, study participants’ experiences may not perfectly mirror those of people navigating PrEP on their own, but the data gleaned will help answer key questions and shape the future of PrEP.

First off, who is interested in using PrEP?

The majority of demonstration projects are enrolling men who have sex with men (MSM for short) and transgender women, who are among those most disproportionately affected by HIV, and who experienced the greatest protective benefit from PrEP in clinical trials. But in the real world, Cohen asked, “will MSM even want to use PrEP? And how is this going to vary based on things like sociodemographics and risk behaviors?”

To start answering these questions, the Demo Project began enrolling MSM and transgender women in September 2012. Potential participants are identified during visits for sexually transmitted infection (STI) testing, although some are referred from community health centers, such as Magnet (San Francisco AIDS Foundation’s sexual health center for gay and bisexual men), or learn about the study elsewhere, such as prepfacts.org.

Between the two study sites, Cohen added, 161 participants have enrolled to date. Of these, roughly 25% are age 25 or younger, and about a third are African-American or Latino.

Results from the project are not expected until late 2014, but “early impressions,” Cohen said, suggest that most participants are interested in PrEP as “an added layer of protection.” Some enrollees report that they do not use condoms, while others want to use PrEP in addition to condoms or as an adjunct to serosorting or seropositioning (that is, choosing whether or how to have sex with partners of the opposite HIV status).

The Demo Project is compiling data not only on individuals who enroll but also about those who decline. Top reasons given for not joining the 48-week project? Lack of time, worry about possible drug side effects, self-perception as at low risk for HIV (given current prevention strategies), and concern about taking a daily medication.

Second, how will people use PrEP?

Outside of the clinical trial setting, “what type of pill-taking practices will we see?” queried Cohen. “And how can we best support and monitor adherence in real-world-type settings?” In clinical trials, the likelihood of acquiring HIV decreased with better adherence; in real-world settings, fitting PrEP into busy lives will be just as important.

Demonstration projects will also need to assess the best ways for people to stop and possibly restart a PrEP regimen, as some may use pre-exposure prophylaxis as a “seasonal” HIV-prevention option. For example, one former PrEP user recently shared online that he took the pill daily for a year and found it worked well for him during a time in his life when he had many different sex partners. He chose to stop using PrEP when he fell in love and “decided to give monogamy a try.”

Third, how will PrEP users’ behaviors change?

In PrEP studies, as in trials of all biomedical HIV prevention tools, participants received the full HIV prevention “package” (free condoms, safer-sex counseling, and testing and treatment for other sexually transmitted infections). And, importantly, participants in these “blinded” clinical trials did not know whether the pills they were taking contained active PrEP drugs or an inactive placebo, or even whether the active drugs would work.

Now that we know PrEP can dramatically reduce HIV infection risk, will PrEP users take the pills and skip the condoms? “How will sexual practices change?” asked Cohen. “Will we see risk compensation and behavioral disinhibition? Will this strengthen sexual partnerships and empower MSM and others at risk for HIV in their HIV prevention strategies?”

Also, what role will safer-sex counseling play in the overall PrEP package? “How much counseling is important, and how often, and what effect does it have, both in promoting adherence and in supporting sexual health behaviors?”

Fourth, will PrEP be tolerable and safe in the real world?

As Cohen put it, “What will the side effect and toxicity profile look like in the implementation context?”

Rigorously controlled trials typically have extensive exclusion criteria to avoid health complications and drug interactions while a new intervention is being tested, but real-world PrEP users may have more complex (and more representative) medical histories and current health issues. What will this mean for the safety of PrEP?

Another concern is the possibility of drug resistance, should individuals acquire HIV while using PrEP (which, on its own, is not designed to suppress the virus in people who are infected). Although past trials have not found this to be a serious risk, will this change in real-world settings?

Finally, where should—and where can—PrEP be offered?

The Demo Project is providing PrEP at a municipal STI clinic, “but there are many potential sites of delivery, including primary care settings and community-based organizations,” said Cohen.

Where will it be feasible to offer pre-exposure prophylaxis? Offering PrEP and monitoring the health of those who use it will require investments of time and money. How can providers be supported in learning about PrEP, offering it to clients and patients, and counseling and monitoring those who opt to use it?

In addition, many health clinics and organizations that serve the most marginalized and most vulnerable to HIV infection are already short on time, funds, and staff. “We need to figure out where and how to deliver PrEP in such a way that it helps to reduce the disparities we see in rates of HIV infection,” Cohen said.

STUDY [sponsor]
iPrEx OLE (Open Label Extension) [NIAID] MSM who previously participated in the iPrEx trial (N=~300) San Francisco, Boston, Chicago Enrollment at U.S. sites completed; results 2014
U.S. PrEP Demonstration Project [NIAID] MSM and transgender women in STI clinics (N=500) San Francisco, Miami Enrollment began September 2012; results 2014
California HIV Research Program [CHRP] MSM and transgender women in STI clinics (N=~700) Los Angeles, Long Beach, Oakland, San Diego Enrolling 2013
Adolescent Trials Network [NICHD] Young MSM:15–17 years (N=100)18–22 years (N=200) Boston, Baltimore, Chicago, Denver, Detroit, Houston, Los Angeles, Memphis, Miami, New Orleans, New York City, Philadelphia, Tampa, Washington, DC Enrollment began 2012
NIH MSM New York City (Callen Lorde Community Health Center) Planning
NIH Serodiscordant couples (N=250 couples) New York City: East Brooklyn, Harlem, South Bronx Planning

Adapted from slide presented by Stephanie Cohen, February 20, 2013.

Is a Demonstration Project Right for You?

PrEP demonstration projects are enrolling around the U.S. Is one a good fit for you? Use these resources to learn more about participating in a PrEP study. (Note that clinical trial listings are not yet available for all demonstration projects.)

Reilly O’Neal is the editor of BETA.



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