Update: Use of HIV drugs shrinks infection risk in uninfected people
Can same pre-exposure prophylaxis results be recreated in real life?
Use of powerful antiretroviral drugs, known as pre-exposure prophylaxis (PrEP), is now being weighed as an addition to the HIV prevention arsenal with the results of a new clinical trial.1
In the Pre-exposure Prophylaxis Initiative (iPrEx) trial, researchers found that among men who have sex with men (MSM) who took a single daily tablet containing two widely used HIV medications, emtricitabine and tenofovir, subjects experienced an average of 43.8% fewer HIV infections than those who received a placebo pill (95% CI 15.4 to 62.6%; P=0.005).1
The iPrEx study, one of the largest HIV prevention clinical trials to focus on men who have sex with men, claims two "firsts:" It is the first HIV prevention study to focus on MSM to be conducted in Africa or Asia, and it is the first demonstration of a biomedical intervention to prevent HIV infection in MSM. The findings represent a "major advance" in HIV prevention research, providing the first evidence that PrEP, when combined with other prevention strategies, can reduce HIV risk among MSM, state the Centers for Disease Control and Prevention (CDC).2 [Use a CDC-developed fact sheet to talk with patients about the ramifications of the study, as well as understand the agency's direction on PrEP. A fact sheet is enclosed.]
The CDC is developing guidance on the safe and effective use of PrEP and determining how to most effectively use it with other prevention strategies to reduce new HIV infections. At press time, interim guidelines tentatively were scheduled to be published in Morbidity and Mortality Weekly Report by the end of February 2011, says Nikki Mayes, a CDC spokesperson. Full U.S. Public Health Service guidelines are anticipated later in 2011, she states.
To conduct the iPrEx study, investigators enrolled 2,499 individuals at high risk of HIV infection in Brazil, Ecuador, Peru, South Africa, Thailand, and the United States. All study participants received a comprehensive package of prevention services designed to reduce their risk of HIV infection throughout the trial, including HIV testing, intensive safer sex counseling, condoms, and treatment and care for sexually transmitted infections. Half of study participants also received the PrEP pill, while the other half received a placebo drug. The pill is marketed by Gilead Sciences of Foster City, CA under the brand name Truvada. Each pill contained 200 mg of emtricitabine and 300 mg of tenofovir.
Investigators recorded 64 HIV infections among the 1,248 study participants who received a placebo pill, while 36 HIV infections were recorded among the 1,251 participants who received the study drug. The average reduction in HIV infection risk of 43.8% includes all study participants, even those who did not take the daily pill consistently.1
PrEP was more protective among those who reported taking the pill more regularly, researchers report. Among those who used the drug on 50% or more of days, as measured by pill counts, bottle counts, and self-reports, risk of HIV infection fell by 50.2% (95% CI 17.9-69.7%; P = 0.006); among those who used the drug on 90% or more of days, as determined by the same measures, the PrEP pill reduced infection risk by 72.8% (95% CI 40.7-87.5%; P = 0.001).1
What's next for PrEP?
PrEP research has been have been hailed by national news media as some of the most important medical achievements of 2010, observes Ward Cates, MD, MPH, president of research at Family Health International in Research Triangle Park, NC. The iPrEX trial follows the 2010 publication of results of the CAPRISA 004 trial, which looked at 1% tenofovir gel. The gel formulation was found to be 39% effective in reducing a woman's risk of becoming infected with HIV during sex and 51% effective in preventing genital herpes infections.3
While the two trials were "diametrically different" in terms of population, site of exposure, and formulation, they both yielded "remarkably similar" results in terms of study endpoints, effectiveness, dosing, and antiretroviral therapy, Cates observes.
For CAPRISA and iPrEX, Cates says the implications for the future of PrEP now center around the following three precepts:
- Biology. Antiretrovirals work for PrEP, if the drug is present at site of exposure, Cates notes.
- Behavior. High adherence is key to PrEP success, just as with condoms, states Cates.
- Impact. Increased coverage is necessary if PrEP is to reduce HIV spread, according to Cates.
PrEP research is ongoing, says Robert Grant, MD, MPH, Betty Jean and Hiro Ogawa endowed investigator at the Gladstone Institute of Virology and Immunology, and associate professor of medicine at the University of California, San Francisco. Grant served as protocol chair for the iPrEX research team.
There are nine studies taking place in several parts of the world that will provide interesting and important information to complement the iPrEx study results in different populations: men and women at risk, serodiscordant couples, and injecting drug users, Grant notes.
"The next steps in PrEP research are being planned in this very moment and have to do basically with the use of PrEP intermittently," Grant says. "The HIV Prevention Trials Network has designed the ADAPT study to evaluate the pharmacokinetics and behaviors associated to the use of PrEP intermittently, (and) the International AIDS Vaccine Initiative is about to be complete or probably completed by now."
There are several research questions still to be answered in the PrEP field, but one of the most important ones are the ones related to the implementation of PrEP programs, says Grant. Demonstration projects should be designed to evaluate the feasibility of PrEP in different parts of the world.
IPrEx will have an open label roll-over extension in which all participants that have been enrolled in the blinded phase of the study can consent to be enrolled in the open label phase targeted at observing changes in sexual and adherence behaviors, he explains. The rollover study also will provide additional information to help determine whether adherence and drug exposure increases, or if risk behavior changes, when trial participants receive the information that the original iPrEx study has provided regarding the safety and efficacy of PrEP.
A more ambitious study that needs to be discussed is a "non-inferiority trial" of daily versus intermittent PrEP, says Grant. This undertaking would be "challenging," he says. Such a study would require a huge sample size, more than 20,000 individuals, the number of participants that are enrolled in all of the PrEP ongoing studies, he notes.
References
- Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010;363:2587-2599.
- Centers for Disease Control and Prevention. Pre-Exposure Prophylaxis (PrEP) for HIV Prevention: Promoting Safe and Effective Use in the United States. Fact sheet. Accessed at: http://www.cdc.gov/nchhstp/newsroom/PrEPforHIVFactSheet.html.
- Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. CAPRISA 004 Trial Group. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010;329:1168-1174.
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