PrEP: A New Tool for HIV Prevention

Pre-exposure prophylaxis, or PrEP, is a new HIV prevention method in which people who do not have HIV infection take a pill daily to reduce their risk of becoming infected. The pill contains medicines that prevent HIV from making new virus as it enters the body. In this way PrEP medicines can help keep the virus from establishing a permanent infection.

Providing a preventive medication before exposure to a germ or virus is not a new practice and has been used to prevent other diseases. For example, when individuals travel to an area where malaria is common, they are advised to take malaria medication before and during travel to prevent getting infected if bitten by a mosquito carrying the malaria parasite. However, the use of medication to prevent HIV infection has only recently been evaluated. When used consistently, PrEP has been shown to reduce the risk of HIV infection among adults at very high risk for HIV infection through sex, including men who have sex with men and heterosexually-active men and women. CDC is also evaluating PrEP's effectiveness in preventing HIV infection among individuals exposed to HIV through injecting drugs, but those results are not yet available.

For some individuals at very high risk for sexual exposure to HIV, PrEP may represent a much-needed additional prevention method -- but it will not be right for everyone. PrEP is an intensive approach that requires strict adherence to daily medication and regular HIV testing. It is not intended to be used in isolation, but rather in combination with other HIV prevention methods. If it is used effectively and by persons at very high risk, PrEP may play a role in helping to reduce the number of new HIV infections in the United States.

PrEP Medications

Most PrEP efficacy trials have tested a combination of the antiretroviral drugs tenofovir disoproxil fumarate (also called TDF, or tenofovir) and emtricitabine (also called FTC), taken in a single pill daily for HIV prevention. This combination pill (brand name Truvada®) was approved by the U.S. Food and Drug Administration (FDA) for use as an HIV treatment in 2004, and was approved as PrEP in July 2012. Some clinical studies have also evaluated the use of tenofovir on its own as a preventive drug, but this drug alone is not FDA-approved as PrEP.

PrEP Proven Safe and Effective in Preventing Sexual HIV Acquisition

Strong research evidence indicates that PrEP, when used consistently, is safe and effective for reducing the risk of acquiring HIV sexually.

Research Among Men Who Have Sex With Men

In November 2010, the multinational iPrEx study showed that a once-daily pill containing tenofovir plus emtricitabine was safe and provided an average of 44 percent additional protection against HIV infection among men who have sex with men (MSM) who were also provided with a comprehensive package of prevention services. These services included provision 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 varied widely depending on how consistently participants used PrEP, with significantly greater levels of protection among those who adhered well to the daily dosing regimen. Among MSM with detectable levels of the medication in their blood, the risk of HIV acquisition was reduced by more than 90 percent.

The iPrEx study followed an earlier study by CDC that examined safety and adherence among MSM in the United States who were using daily tenofovir alone. The study found that the regimen was safe and did not lead to increases in risk behavior.

Research Among Heterosexually-Active Men and Women

In July 2011, researchers announced the results of two PrEP studies finding strong evidence that PrEP is effective and safe among heterosexually-active men and women.

• The TDF2 study found that a once-daily tablet containing tenofovir plus emtricitabine reduced the risk of acquiring HIV infection by roughly 62 percent overall in the study population of uninfected heterosexually-active men and women.
• The Partners PrEP study found that that daily doses of tenofovir plus emtricitabine or daily doses of tenofovir alone reduced HIV transmission among heterosexual serodiscordant couples (in which one partner is infected with HIV and the other is not) by 75 percent and 67 percent, respectively. The trial found that PrEP was equally effective among men and women, and that there was no statistically significant difference in efficacy between the two medication regimens.

As with the iPrEx study, both TDF2 and Partners PrEP showed that the level of protection offered by PrEP is strongly related to the level of adherence to the daily medication doses.

• In Partners PrEP, participants in the tenofovir-plus-emtricitabine group with detectable levels of the medication experienced a 90 percent reduction in risk for HIV infection; in the tenofovir- only group, the presence of medication in the blood was associated with an 86 percent reduction in risk.
• In TDF2, only half of the participants in the tenofovir-plus-emtricitabine group who became infected with HIV had any detectable medication in their blood, and even those participants had very low levels of medication present. This suggests that they had not taken PrEP consistently. In contrast, over 80 percent of matched participants who remained uninfected had detectable medication in their blood and the average medication level was substantially higher.

Two other research studies also reported results in 2011: a study called FEM-PrEP examining PrEP with tenofovir plus emtricitabine and a single group of participants in the VOICE trial examining PrEP with oral tenofovir alone did not show a protective effect among heterosexually-active women. Further sub-analysis of a sample of women in the FEM-PrEP trial showed that fewer than half of women assigned to take tenofovir plus emtricitabine were actually taking the drug, indicating that lack of adherence was likely a major factor contributing to the lack of efficacy in that trial.

Other than low adherence, no factors have yet been identified that appear to influence the efficacy of PrEP in reducing sexual transmission of HIV. The VOICE trial, which is still evaluating daily oral tenofovir plus emtricitabine in women, remains underway and may provide additional insight once those results are available.