PrEP: A New Approach to HIV Prevention
New tools to prevent HIV are urgently needed to stem the estimated 2.6 million new HIV infections that occur worldwide each year. Recent research has shown that a new approach called pre-exposure prophylaxis, or PrEP, can reduce the risk of contracting HIV in gay and bisexual men at high risk of infection, when combined with existing prevention measures. Ongoing studies are evaluating this approach in other populations at risk for HIV, including heterosexuals and injection drug users.
In this new approach to HIV prevention, people who are uninfected take an HIV treatment pill daily to reduce their risk of becoming infected. By inhibiting HIV from replicating as it enters the body, PrEP can prevent the virus from establishing permanent infection. The concept of providing a preventative treatment before exposure to an infectious agent is not new. For example, when individuals travel to an area where malaria is common, they are advised to take malaria treatment medication before and during travel to prevent illness.
As part of its commitment to developing new HIV prevention strategies, the Centers for Disease Control and Prevention has sponsored several clinical trials to evaluate the safety and efficacy of PrEP for HIV prevention.
Characteristics of Current PrEP Candidates
- Established safety as HIV treatments
- Potent antiretrovirals
- Long duration of action
- Once-daily dosing
- Low levels of resistance
Current PrEP trials, including those sponsored by CDC, are testing the antiretroviral drug tenofovir disoproxil fumarate (or tenofovir, brand name Viread®) used alone or in combination with emtricitabine (together, known as the brand name Truvada®) taken as a preventative drug.
Tenofovir was approved by the U.S. Food and Drug Administration in 2001 as a treatment for HIV infection, and the tenofovir plus emtricitabine combination pill was approved for use as an HIV treatment in 2004. Data from Gilead Sciences, Inc., the manufacturer of the drugs, indicate that more than one million HIV-infected people around the world have now used these drugs. As treatments for HIV-infected individuals, tenofovir and tenofovir plus emtricitabine have been shown to be both safe and effective. They have relatively low levels of side effects and slow development of associated drug resistance, compared with other available HIV treatments.
PrEP Proven Safe and Effective in Gay and Bisexual Men
In a major advance in HIV prevention research, investigators recently reported that PrEP is safe and effective in preventing HIV infection -- when combined with other comprehensive prevention approaches -- among men who have sex with men who are at high risk of HIV infection.
In November 2010, the National Institutes of Health (NIH) announced results from a multinational, randomized, double-blind, placebo-controlled, phase III clinical trial of tenofovir plus emtricitabine to prevent HIV infection.
The iPrEX trial showed that a once-daily pill containing tenofovir plus emtricitabine was safe and provided an average of 44 percent additional protection against HIV infection to men who have sex with men and transgendered women who have sex with men, who also received a comprehensive package of prevention services. These services included use of condoms, monthly HIV testing, counseling to reduce risk behavior and encourage adherence to the daily pill regimen, and management of other sexually transmitted infections.
The level of protection shown varied widely depending on how consistently participants used PrEP. Among those whose data (based on self-reports, bottles dispensed, and pill counts) indicate use on 90 percent or more days, HIV risk was reduced by roughly 73 percent, while among those whose adherence by the same measure was less than 90 percent, HIV risk was reduced by only about 21 percent.
CDC U.S. Tenofovir Extended Safety Trial
In July 2010, CDC reported results of a Phase II extended safety trial examining the clinical and behavioral safety of once- daily oral PrEP with tenofovir and adherence to the drug among gay and bisexual men in the United States.
The study was conducted at three sites in collaboration with the San Francisco Department of Public Health, the AIDS Research Consortium of Atlanta, and Fenway Community Health in Boston. The study enrolled 400 HIV-negative MSM who reported having had anal intercourse with a man in the prior 12 months. Participants were randomly assigned to one of four study arms. Two arms received either tenofovir or placebo immediately upon enrollment, while the other two arms received either tenofovir or placebo after nine months of enrollment. This design allowed researchers to compare risk behaviors among those taking a daily pill and those not taking pills.
Preliminary analyses suggest no serious safety concerns. While analysis of behavioral safety data are not yet complete, preliminary analyses suggest there was no increased risk in men taking a study pill compared to those not taking a study pill during their first nine months of study participation. Additional analyses of clinical, behavioral, and adherence data are underway.
CDC-Sponsored PrEP Trials -- Botswana and Thailand
CDC is sponsoring additional clinical trials that are designed to answer important questions about the safety and efficacy of a tenofovir or tenofovir plus emtricitabine pill taken as a daily oral HIV preventative among populations at high risk for infection -- heterosexuals in Botswana and injection drug users in Thailand. Both trials are assessing the effects of taking a daily pill on HIV risk behaviors, adherence to and acceptability of the regimen, and in cases where participants become HIV- infected, the resistance characteristics of the acquired virus. Importantly, the trial in Thailand will also examine the efficacy of PrEP in preventing HIV infection among injection drug users.
|Objective||Evaluate clinical and behavioral safety of and adherence to PrEP regimen among heterosexuals||Evaluate PrEP safety and efficacy among intravenous drug users (IDUs)|
|Drug||Tenofovir plus emtricitabine||Tenofovir|
|Participants||1,200 HIV-negative heterosexual men and women in urban areas||2,400 HIV-negative IDUs at 17 drug treatment clinics in Bangkok|
|Results Anticipated||Mid-2011||Early 2012|