By DR. ROBERT GRANT & DR. ALBERT LIU
A robust public debate is underway about the potential use of anti-HIV drugs to prevent HIV infection (also known as pre-exposure prophylaxis or PrEP). Our study, called iPrEx, provided the first conclusive evidence that the daily use of PrEP with the FDA-approved HIV treatment Truvada® can significantly reduce HIV infection risk in gay, bisexual and other men who have sex with men (MSM) and transgender women, when delivered as part of a comprehensive package of prevention services, including condoms. The protection provided by PrEP and condoms together could have a substantial impact in reducing new HIV infections among MSM worldwide.
Recently, a private healthcare provider has begun a paid advertising campaign urging the FDA not to even consider approving the use of PrEP – charging, among other things, that MSM will stop using condoms if PrEP is permitted. The pros and cons of PrEP use should be vigorously debated — but that debate should be based on facts, rather than the assumption that MSM will not act to protect themselves and others from infection. Here are the facts about the iPrEX study:
• A diverse group of 2,499 HIV-negative MSM and transgender women on four continents with a range of sexual practices participated in iPrEx. All participants received a comprehensive package of HIV prevention services. Half also received Truvada, while the other half received a placebo (blank pill). Neither the study participants nor the investigators knew which pill they received during the study.
• The group that received PrEP with Truvada in addition to condoms had 44 percent fewer HIV infections. This protective effect was seen across different groups in the study, including those of different age, ethnicity and education level.
• Men in both study groups reduced their risk behaviors and increased their condom use – demonstrating that MSM can use PrEP and condoms together. PrEP does not protect against other sexually transmitted infections and should never be considered as a substitute for condom use or other safer sex precautions.
• Ensuring daily pill use will be critical to the success of PrEP. While many iPrEx study participants used the pill consistently, about 50 percent did not, which impacted the effectiveness of PrEP in the study. Among those who took the medication consistently, the level of protection PrEP provided reached 72 to 95 percent. A second phase of the iPrEx study will begin soon, in which all participants who want PrEP will receive it. We are hoping to learn whether knowing that PrEP works will help participants achieve higher rates of pill use and protection in this phase of the study.
• Truvada is widely used for HIV treatment because it is generally well tolerated. Rates of side effects were very low in the iPrEx study. A small amount of bone loss was seen among those receiving PrEP, a finding commonly seen in HIV-positive individuals starting anti-HIV treatment; these changes had no apparent negative health impact. Studies to date also show no evidence of HIV drug resistance associated with PrEP use. HIV testing and medical evaluation before starting PrEP and while using PrEP are important to prevent resistance.
• A daily PrEP dosing regimen was used in the iPrEx study. It is not known whether PrEP can be taken less frequently to prevent HIV infections. Additional studies are underway or being planned to look at whether different dosing regimens (e.g., taking PrEP before and after sex, or on a regular schedule several times a week) would be safe and effective.
• The iPrEx study was paid for by the U.S. National Institutes of Health and by the Bill & Melinda Gates Foundation, and was not organized or run by any drug company. IPrEx requested and received a donation of study drug from Gilead Sciences, but Gilead had no other input into the study.
Much more work lies ahead to determine whether PrEP can help stop HIV infections in other populations, such as heterosexuals and injection drug users, to better understand possible side effects of PrEP, to support consistent pill use among people who want to use it, and to ensure that PrEP is seen as one element of an HIV prevention strategy that includes regular condom use. It will also be critical to address issues of cost, and to determine how to ensure that PrEP will be available to MSM in the United States and around the world who need it most.
Additional studies are also underway to test whether other anti-HIV medicines (including pills, gels, and other formulations) are safe and effective for HIV prevention.
We believe that MSM and all communities working to protect themselves and reduce the impact of the HIV epidemic have the right to full information about PrEP, and can make informed, intelligent decisions about whether or not to utilize PrEP as one component of a comprehensive HIV prevention strategy. The iPrEx study investigators are committed to providing complete information about the study findings to help ensure that those decisions are made based on the facts about PrEP.
Dr. Robert Grant is iPrEx protocol chair. Dr. Albert Liu is iPrEx medical officer and San Francisco Site Researcher. This column was co-signed by two additional site researchers and two investigators.