Many Gay Men Interested in PrEP, Experts Create Road Map

Nearly half of U.S. gay/bisexual men said they would be "very likely" to use antiretroviral drugs as pre-exposure prophylaxis (PrEP) if it significantly reduces the risk of HIV infection. Another recent study explored the effect of PrEP on condom use. These findings further inform the sometimes contentious debate about how effective PrEP will be in "real world" use, whether benefits outweigh risks, and how to provide access.

Last November researchers reported preliminary findings from the large international iPrEx study, showing that a daily combination of tenofovir plus emtricitabine (the drugs in Truvada) reduced the risk of HIV acquisition by 44% for men who have sex with men (MSM).

Further iPrEx findings presented at the International AIDS Society (IAS) conference this past July showed that PrEP effectiveness reached 92% for participants with good adherence as demonstrated by detectable drug in their blood. The TDF2 and Partners PrEP trials, also presented at that meeting, found that PrEP was effective for heterosexual couples.

The iPrEx findings drew acclaim from many HIV/AIDS organizations. But some experts were less enthusiastic, noting that the reduction in HIV infections was not as impressive as headlines made it seem. The overall relative risk reduction of 44% reflects a decrease in absolute risk from 5.1% to 2.8% -- both very small numbers.

U.S. Internet Survey

As reported at the recent National HIV Prevention Conference in August, Patrick Sullivan from Emory University, Susan Buchbinder from the San Francisco Department of Public Health, and colleagues conducted an online survey of gay and bisexual men between November 30 and December 14, 2010, right after the initial iPrEx findings garnered widespread media attention.

Men recruited through Facebook and Black Gay Chat were asked to answer questionnaires about awareness of and intention to use PrEP. Eligible participants were at least 18 years of age, had at least 1 male sex partner during the past 12 months, and identified themselves as HIV negative.

A total of 1333 men completed the questionnaire and were included in the analysis. The median age was 28 years and 36% had at least a college education; 71% were white, 13% were Latino/Hispanic; and 8% were black. Nearly one-quarter (22%) reported having unprotected anal intercourse the last time they had sex.

Results

• 29% of participants reported having heard about the iPrEx results.
• Most learned about the study from the Internet (60%) or from a newspaper or magazine (27%).
• 47% of respondents reported being extremely likely or very likely to use PrEP after being told about the iPrEx results.
• 17% of the men reported being not at all likely to use PrEP.
• Including men who said they were somewhat likely, about two-thirds expressed some degree of intent to use PrEP.
• Black and Hispanic men expressed a higher level of intent to use PrEP than white men (adjusted odd ratio [aOR] 1.9 and 1.5, respectively).
• Men with higher levels of education were less likely to say they would use PrEP (aOR 0.7).
• Age, geographic region, and having recent receptive anal intercourse did not significantly influence intent to use PrEP.
• About half the participants said they believed PrEP would lower their individual risk of acquiring HIV, rather than decreasing risk on a population level.
• 17% said they were unsure what the study results meant.

"In the 3 weeks after the announcement of the iPrEx results, most Internet-using MSM in our survey were unaware of the study results, and most did not correctly interpret the results," the researchers concluded. "However, nearly half reported being very likely to use PrEP...Additional outreach and education to MSM communities about PrEP will be important in the early phases of PrEP implementation in the United States."

PrEP and Condom Use

In related research described in the July 13, 2011, advance online edition of Journal of Acquired Immune Deficiency Syndromes, Beryl Koblin and fellow investigators with the Project MIX Study Team looked at decision-making about condom use given hypothetical scenarios of PrEP efficacy among gay/bisexual men who use alcohol or drugs during sex. Studies indicate that this population is less likely to regularly practice safer sex and more likely to contract HIV.

Some public health officials and advocates in the PrEP debate have expressed concern about "behavioral disinhibition," or the tendency to forgo safer sex practices such as condom use if people believe antiretroviral drugs will protect them from infection.

The Project MIX researchers recruited 645 HIV negative substance-using MSM in 4 U.S. cities (Chicago, Los Angeles, New York, and San Francisco). The age range was 18-67 years, with a majority under age 35. They reported recent unprotected anal sex with a male partner who was HIV positive or of unknown status; 15 said they had previously used antiretroviral drugs as PrEP, but none had used the tenofovir/emtricitabine regimen used in iPrEx.

Participants were classified into 3 groups:

• Men who said PrEP would have to be almost always or always effective in order to stop using condoms for receptive or insertive anal intercourse (high efficacy);
• Men who said PreP would have to be effective at least half the time, reflecting the actual overall efficacy in the iPrEx trial (mid-range efficacy);
• Men who said they would stop using condoms if PrEP were effective less than half the time (low efficacy).

Results

• 73% of the men said they would require high efficacy to forgo condoms for receptive anal sex, and 49% said the same for insertive anal sex.
• 15% said they would require mid-range efficacy to forgo condoms for receptive anal sex, and 34% for insertive anal sex.
• 12% said they would forgo condoms for receptive anal sex and 17% for insertive anal sex even if PrEP efficacy is low.
• Men who fell into the mid-range PrEP efficacy group reported more difficulty communicating about safer sex after using alcohol or drugs than men in the high or low efficacy groups.
• Men who gave different efficacy levels when considering receptive versus insertive anal sex reported more communication difficulties and lower intention to use condoms.

Based on these findings, the study authors concluded, "Communication about safer sex while under the influence of alcohol or other substances and condom intentions are important factors to consider for HIV prevention interventions for PrEP users."

PrEP Roadmap

On August 19 more than 200 researchers, advocates, public health officials, pharmaceutical industry representatives, and other stakeholders took part in a public meeting in Washington, DC, accompanied by an interactive webcast, to discuss the findings from iPrEX and the other recent PrEP trials.

Convened by the Forum for Collaborative HIV Research, the meeting aimed to devise a "roadmap" to help the FDA and CDC develop guidance on PrEP use by healthy individuals at high risk of acquiring HIV. Gilead Sciences announced earlier this year that it plans to request FDA approval of Truvada for PrEP.

"We now have findings from large studies that support a conclusion that PrEP is effective in gay and bisexual men, who represent more than half of new HIV infections in the U.S., and now, there is evidence that PrEP may reduce HIV infection in heterosexual men and women, the population hardest hit by HIV worldwide," said Jur Strobos, MD, Deputy Director of the Forum in a press release issued by the organization.

"We must however, apply these promising data to develop workable strategies that mitigate risk that may be associated with the prophylactic use of antiretrovirals," he continued. "These include both medical and socio-behavioral risk. We must ensure that people at greatest risk for acquiring HIV receive a comprehensive package of prevention services, including regular HIV testing, condom provision, risk reduction counseling and management of other sexually transmitted infections. The purpose of our meeting was to help identify what the components of a complete package should be."

One issue under discussion was how the FDA would evaluate an indication for healthy HIV negative people, considering that tenofovir can cause side effects including kidney problems and bone loss, and its long-term toxicities are not yet fully understood. Drug resistance is also a concern, especially if people use PrEP when they are already -- perhaps unknowingly -- HIV positive.

Conference participants urged healthcare providers and the public to wait for further guidance before using PrEP, but if a provider thinks PrEP is urgent for a specific patient, they can follow the procedures for MSM issued by the CDC last winter, available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6003a1.htm?s_cid=mm6003a1_w. 

The Forum for Collaborative HIV Research has posted the webcast of the meeting and plans to publish the proceedings. The full press release, which includes more detail about cautions and considerations surrounding PrEP, is available at http://www.hivforum.org/index.php?option=com_content&task=view&id=442&Itemid=79.

PrEP Perspectives

Two major medical journals recently published items about PrEP in the wake of trial findings reported during the past year.

In a news overview in the August 16, 2011, issue of Nature, Erika Check Hayden focused on the risks of widespread use of PrEP.

"[P]eople taking the drugs may adopt riskier behaviors because they feel protected -- a phenomenon known as 'risk disinhibition' -- undermining the benefit of the drugs and potentially infecting others," she wrote. "Moreover, those who become infected while taking the preventive regimen might develop drug-resistant viruses that they could then transmit to others.”

The recent trials did not find evidence of behavioral disinhibition and development of resistance was rare, but those studies delivered PrEP in a context of intensive risk-reduction counseling, support for adherence, and frequent HIV testing -- "very different from the real world."

"Deciding who to treat with PrEP could also be a challenge," Hayden wrote. HIV infection rates are rising among young men, "Yet if these men aren't using the prevention measures already available, there's little reason to think doctors will have an easier time convincing them to take a daily pill."

PrEP is also sure to be a contentious issue in resource-limited settings where many HIV positive people are not able to access antiretroviral drugs they need for their own health.

Although the cost-effectiveness of PrEP increases in higher-risk populations, Hayden noted the political difficulty of providing therapy for the most at-risk groups. In the words of prevention researcher Myron Cohen, who presented data from the HPTN 052 treatment-as-prevention study at the IAS meeting: "Even if you thought the best use of the pills would be for sex workers, it would be very difficult to take a limited supply of pills and give them to high-risk populations at the expense of people who are dying of infection."

Describing the July IAS meeting, an editorial in the September 2011 issue of Lancet Infectious Diseases states, "A broad diversity of topics from basic research to program implementation was covered, but the conference was dominated by one message that was repeated time and again in the press conferences, scientific sessions, and the rapporteur summaries: 'treatment is prevention.' The phrase became something of a mantra."

"The findings of these studies are certainly encouraging and the addition of antiretroviral drugs to the armamentarium of approaches to prevent the transmission of HIV is to be welcomed," the editorial continued. "The past 30 years have shown that reductions in HIV transmission and the burden of AIDS rely on a combination of approaches that need to be tailored, adapted, and selected on the basis of the specific situations and populations."

But here too, the authors urged caution with regard to cost, access, resistance, and behavioral disinhibition.

"Integration of antiretroviral prophylaxis into HIV prevention strategies must not be at the expense of tried and tested behavioral interventions, and care must be taken to safeguard the usefulness of these drugs for treatment in the future and to encourage a healthy drug-development pipeline," the authors concluded. "The fight against HIV/AIDS is a long-game, and current enthusiasm for positive results must lead to approaches that are sustainable in the long-term."

9/6/11

References

P Sullivan, A Liu, J Fuchs S Buchbinder, et al. Awareness of and Intention to Use PrEP: A Post-iPrEx Survey of U.S. MSM. National HIV Prevention Conference. Atlanta, August 14-17, 2011. Abstract 1978.

BA Koblin, G Mansergh, V Frye, and others (Project MIX Study Team. Condomuse decision making in the context of hypothetical pre-exposure prophylaxis efficacy among substance-using men who have sex with men: Project MIX. Journal of Acquired Immune Deficiency Syndromes (abstract) July 13, 2011 (Epub ahead of print).

EC Hayden. HIV drug-prevention strategy carries risks. Nature 476(7360):260-1 (full text). August 16, 2011. 

Editorial. Treatment as prevention for HIV. Lancet Infectious Diseases 11(9): 651 (full text). September 2011.

Other Source

Forum for Collaborative HIV Research. HIV Experts Create the Roadmap for Providing PrEP to Uninfected Individuals to Reduce the Risk of HIV Infection. Press release. August 24, 2011.