The Centers for Disease Control and Prevention (CDC) took a major step toward transforming HIV prevention in the U.S. May 14 by recommending that health-care providers consider prescribing pre-exposure prophylaxis (PrEP) to uninfected patients at substantial risk of becoming infected. The CDC issued new clinical guidelines that could lead to a significant expansion of PrEP use by gay and bisexual men, heterosexual women and men, and injection drug users.
The new CDC guidelines build on a review of the data from several studies in recent years that showed that HIV-uninfected individuals who take specific antiretroviral medications -- a practice known as pre-exposure chemoprophylaxis (aka "PrEP") -- could significantly lower their risk of becoming infected. The idea of PrEP to prevent infections is not new. For example, before people go to countries that have high concentrations of malaria-transmitting mosquitos, they may take antimalarial drugs as a preventive strategy. PrEP works by ensuring that medication is present in the body that prevents an exposure becoming an established infection. The CDC noted that "[w]hen taken daily as directed, PrEP can reduce the risk of HIV infection by more than 90 percent. Inconsistent use results in much lower levels of protection." In other words, consistent daily PrEP use is comparable to, if not more protective than, using condoms in the real world. A number of studies conducted over the past quarter century have found that people who reported consistent condom use reduced their risk of HIV transmission during anal sex by 70 to 87 percent and reduced the risk of HIV transmission during vaginal sex by 80 to 85 percent.
The guidelines recommend that PrEP be considered for the following types of HIV-uninfected patients:
- Anyone who is in an ongoing sexual relationship with an HIV-infected partner.
- A gay or bisexual man who has had sex without a condom or has been diagnosed with a sexually transmitted infection within the past six months and is not in a mutually monogamous relationship with a partner who recently tested HIV-negative.
- A heterosexual man or woman who does not always use condoms when having sex with partners known to be at risk for HIV (for example, injecting drug users or bisexual male partners of unknown HIV status) and is not in a mutually monogamous relationship with a partner who recently tested HIV-negative.
- Anyone who has, within the past six months, injected illicit drugs and shared equipment or been in a treatment program for injection drug use.
The CDC estimates that approximately 500,000 Americans would be eligible for PrEP use, according to the above criteria. If some of those at risk for HIV infection use PrEP, the 50,000 new HIV infections that have been occurring in the U.S. each year could be reduced. Modeling studies suggest the most effective deployment of PrEP will be in combination with scaled-up HIV treatment of people who are known to be HIV-infected, as this was also shown to reduce infections. Recent modeling of PrEP implementation coupled with scaled-up HIV treatment predicts that PrEP could significantly reduce HIV incidence and prevalence, saving health-care costs and lost economic productivity.
In response to clinical research trials that showed that taking a daily regimen of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) lowered the risk of HIV infection among men who have sex with men and heterosexual men and women, in July 2012 the U.S. Food and Drug Administration approved the use of TDF/FTC for PrEP. A subsequent study showed that PrEP could lower the risk for injection drug users.
Some have raised concerns about PrEP related to potential side effects, risk compensation (the idea that people will stop using condoms if PrEP becomes available), and non-adherence leading to antiretroviral drug resistance. However, a review of five major clinical trials involving about 6,000 participants by the Forum for Collaborative HIV Research, a nonprofit think tank, found no concerning increases in side effects, risk compensation, or development of drug resistance in participants. Ongoing monitoring of PrEP safety in the real world is being done in several demonstration projects in the U.S. and around the world, and so far there are no red flags. This is not to say that if a person does not consistently take the medication and/or does not follow up in care, there can't be problems, but the CDC's guidelines make it clear that in weighing the evidence, the good outweighed the bad.
There were two studies of PrEP in young African women that did not demonstrate benefit because many of the participants did not adhere to taking the pill once a day. In other words, PrEP will not work if people don't take it. PrEP is a medical intervention, and people who want to use it should find providers who are knowledgeable and supportive. The new CDC guidelines stress that potential candidates for PrEP should be tested for HIV and have other safety lab tests done before it is prescribed, and they should be monitored at least every three months while using PrEP. If people suspect that they have become infected with HIV around the time they used PrEP, they should discontinue PrEP use immediately and see a provider in order to minimize the risk of developing drug-resistant HIV.
Fenway Health and The Fenway Institute commend the CDC for acting relatively quickly on recent scientific developments and urging providers to consider PrEP as an option for their patients. As Jonathan Mermin, Director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, told The New York Times, "On average, it takes a decade for a scientific breakthrough to be adopted. We hope we can shorten that time frame and increase people's survival." While condoms and lubricant are a proven method for preventing sexual transmission of HIV, many individuals are not using condoms and could benefit from PrEP.
More than 30 years after the first cases of AIDS were diagnosed, some 1.2 million Americans are living with HIV, and 600,000 people with AIDS have died in our country. Every year in the U.S., among the roughly 50,000 individuals who are newly infected, two thirds are gay and bisexual men and transgender women, and African Americans are disproportionately affected among all ethnic and racial groups in the U.S. It's time for an all-hands-on-deck approach. We must use every tool in our toolkit to prevent new infections. This includes condoms and lubricants, syringe exchange, and safer sex education. And it also includes PrEP.
Sean Cahill, Ph.D., is Director of Health Policy Research at The Fenway Institute. Kenneth Mayer, M.D., is Medical Research Director and Co-Chair of The Fenway Institute, Infectious Disease Attending and Director of HIV Prevention Research at Beth Israel Deaconess Medical Center, and Professor of Medicine at Harvard Medical School.