The U.S. Centers for Disease Control and Prevention (CDC) has released interim guidance for the use of antiretroviral medication as pre-exposure prophylaxis (PrEP) for high-risk gay and bisexual men who have sex with men (MSM) in the United States. The guidance was released in this week’s edition of Morbidity and Mortality Weekly Report (MMWR).
“For MSM whose behaviors place them at high risk for HIV infection and who do not use other effective prevention methods consistently, PrEP might reduce their risk for HIV infection,” according to MMWR.
The guidelines come in response to the Pre-exposure Prophylaxis Initiative (iPrEX) trial results that came out in late November, which showed that daily oral dosing of the antiretroviral drugs tenofovir and emtricitabine combined into one tablet (Truvada) indicated a 44 percent reduction in the incidence of HIV among MSM at high risk of infection. This result was highly dependent on treatment adherence – a key concern in the CDC interim guidance.
Since the release of the iPrEX results, there have been reports of health care providers prescribing Truvada to their high-risk patients. “Confirmatory trials for this population are neither planned nor likely to occur, given the clear evidence of efficacy in the iPrEx trial, especially with high adherence,” said Jennifer Horvath, a CDC spokesperson. “Because PrEP with Truvada has now been proven effective and is already available for off-label use with a prescription, CDC recognizes that there may be high-risk MSM and physicians seeking to use PrEP immediately.”
“Concerns exist that without early guidance, various unsafe and potentially less effective PrEP-related practices could develop among health-care providers and MSM beginning to use PrEP in the coming weeks and months,” the MMWR states. Some of the concerns the CDC highlights are use of antiretrovirals other than Truvada for this PrEP, dosing schedules of unproven efficacy, not screening for acute infection, lack of routine repeat HIV testing, and providing prescriptions without counseling on other HIV prevention interventions.
The interim guidance also warns that until the safety and efficacy of PrEP is determined in trials now under way with populations at high risk for HIV acquisition by other routes of transmission, PrEP should be considered only for MSM. There are many ongoing trials in various phases of development. AVAC, a global advocacy group for HIV prevention, has a comprehensive chart showing the status and particulars of ongoing daily, oral PrEP trials in various at-risk populations including: The Bangkok Tenofovir Study among injecting drug users; the Partners PrEP trial among serodiscordant heterosexual couples in Kenya and Uganda; and the FEM-PrEP trial among heterosexual women in Kenya, South Africa, Tanzania and Zimbabwe. The chart lists other oral PrEP trials and PrEP topical gel trails as well, such as the VOICE trial which is looking at both oral and topical PrEP among heterosexual women in South Africa, Uganda and Zimbabwe.
“As an HIV vaccine is currently not available or on the horizon, [the iPrEx] results have generated a lot of excitement and interest,” said John Martin, chair and CEO of Gilead Sciences, maker of Truvada. “We intend to submit a New Drug Application to the U.S. FDA in the first half of this year for the use of Truvada in the prevention of HIV infection. While we don’t view a potential prophylaxis indication as a second commercial opportunity, we do see it as an important contribution to the management of HIV epidemic worldwide,” Martin said.
It is worth noting that the cost of Truvada is nearly $1,000 per month, with most insurance companies unlikely to provide coverage for Truvada as prevention, at least until the FDA approves it for this purpose.
In a world where resources are already scarce, an issue that begs discussion will be how to provide HIV medications as prophylaxis when there are many who are already infected that are not receiving the treatment they need. Also a concern to some care providers, the CDC interim guidance does not call for experienced HIV providers to manage and prescribe this intervention. Such issues might need to be fleshed out if and when comprehensive guidelines are released.