April 20, 2011
The iPrEx study, conducted among 2,499 gay and bisexual men and female transgenders at high risk for HIV-infection in the US, South Africa, South America and Thailand, reported extremely hopeful results about the effectiveness of taking the antiretroviral Truvada daily in combination with safe sex and condom use counseling to prevent HIV infection. Overall results showed that 44 percent fewer men — 35 actual people — avoided becoming infected with HIV while taking Truvada than those taking a placebo. Men who took Truvada daily at least 90 percent of the time were between 70 and 90 percent less likely to become infected with HIV than those not taking it.
Following the release of iPrEx data, the Centers for Disease Control & Prevention (CDC) released interim guidance to clinicians about how to offer PrEP to patients, and there is evidence that some individuals are now being prescribed Truvada for prevention. Project Inform participated in developing that interim guidance. The CDC plans to issue more thorough guidance later this year with input from additional stakeholders. Some private insurance companies have indicated that they are paying for Truvada when prescribed for PrEP even though this is currently an ‘off-label’ use, meaning that Truvada is currently only approved by the FDA for the treatment of HIV.
Based on the iPrEx results, Project Inform is actively working with other prevention advocacy groups to press for federal and private funding of at least four demonstration projects across the country to determine whether PrEP can be as, or perhaps more, effective when delivered in community based settings as in a carefully controlled clinical trial. Among the key questions to be answered in these demonstration projects are:
- Who should PrEP be targeted to in order to have maximum impact on new cases of HIV infection, and will the target groups we would most like to see use PrEP actually participate in demonstration projects?
- In what clinical settings are participants most likely to fully participate in the full PrEP regimen of daily pill-taking, ongoing behavioral counseling and medical monitoring?
- Will participants in demonstration projects resort to taking PrEP only intermittently, or will they share drug with others? What strategies might assure strong adherence to taking Truvada daily, as is necessary to assuring the best possible protection?
- Will taking Truvada daily cause participants to reduce their adherence to safe sex as a necessary part of the PrEP package, and what strategies might be the most effective in encouraging the ongoing practice of safe sex while also taking Truvada?
- Will PrEP be shown to be substantially effective in preventing new infections among participants without significant side effects or development of drug resistance?
Project Inform and its advocacy partners are also prepared to support the planned effort by Gilead Sciences, the manufacturer of Truvada, to seek FDA approval to use PrEP for prevention purposes in gay and bisexual men on the strength of the iPrEx data. This licensing of Truvada for prevention is important to assuring that clinicians are comfortable prescribing PrEP and that all insurers, particularly public programs like Medicaid, will pay for the medication for this purpose.
In March, Project Inform joined many other HIV agencies in responding to an advertising campaign launched by the AIDS Health Care Foundation (AHF) attacking Gilead for its plan to seek FDA approval for Truvada for prevention. Â Ignoring the whole body of data suggesting that when iPrEx study participants took Truvada regularly, it was in fact highly effective, AHF argued that overall effectiveness of 44 percent is inadequate to proceed any further with PrEP.
It is true that fifty percent of iPrEx participants did not take Truvada daily or even at all. But 52 percent fewer participants who reported that they sometimes had unprotected receptive anal intercourse (URAI), the highest risk activity for acquiring HIV, and who took the drug 50 percent of the time or more, avoided becoming infected when taking Truvada. Many of the participants who reported that they were not taking Truvada daily also reported that they were not having sex and therefore did not see the reason for taking the pill. But among participants who were having regular sex, and particularly among those having URAI, adherence to daily Truvada was much higher, and PrEP effectiveness was as high as 90 percent.
Project Inform feels strongly that, based on the strength of these data, it would be irresponsible and unethical not to make PrEP available to high risk gay and bisexual men and female transgenders who choose it and are able to adhere to daily use of Truvada – even as we await the results of demonstration projects seeking to determine how effective more widespread use of PrEP might be. We will therefore work with our advocacy partners to support a request to the FDA for approval of Truvada for prevention.
On April 18, it was announced that a second study of PrEP using Truvada in 2,000 African women called FEM-PrEP was stopped early due to a significant number of new infections occurring among participants. The reasons for this failure are not completely known at this time, and the investigators will issue a report in coming months explaining their findings. It is believed that poor adherence to daily use of Truvada, the inability of Truvada to penetrate cells and tissues of the vagina, or higher rates of unprotected sex as a result of pill taking might explain this very disappointing problem.
The FEM-PrEP data stand in stark contrast to data reported earlier from the CAPRISA study in which the drug Tenofovir (one of two drugs in Truvada) placed in a gel for insertion in the vagina, provided very similar protection as shown in iPrEx. Once again, good adherence to using Tenofovir correlated heavily with the level of protection women received against HIV infection.
Still, given the huge number of HIV infections that continue to affect women globally, PrEP has been looked to as a potentially important prevention intervention in large part because it would give users greater control in situations where a partner will not use a condom or uses them incorrectly. Two other ongoing trials in sub-Saharan Africa are evaluating oral Truvada and Tenofovir among heterosexuals. The VOICE trial is evaluating oral Tenofovir and Truvada, as well as 1% Tenofovir gel in 5,000 women in sub-Saharan Africa. Partners PrEP is evaluating oral Tenofovir and Truvada in the HIV-negative member of couples in which one partner is HIV-infected. In the interest of protecting these large and vulnerable populations, we hope for strong results from these studies. It is also possible that future trials of other antiretrovirals for PrEP will show greater effectiveness in penetrating vaginal tissue and providing protection against HIV for women.
AHF has used the failure of FEM-PrEP to argue even more aggressively that the FDA should not license Truvada for PrEP, asserting that the world should instead be focused on assuring that more HIV-positive people know their HIV status and are engaged in treatment as a form of prevention. Project Inform strongly agrees that a global effort to expand testing and linkage to care and treatment will prevent many new HIV infections, and we have been significant advocates for this approach. But we also believe that people who are at risk of becoming newly infected with HIV need and deserve to have additional choices for how to protect themselves from becoming infected, and that PrEP still holds out that possibility. The fact that FEM-PrEP failed, for reasons that we don’t currently understand, does not mean that the results of iPrEx are somehow nullified. Efforts to further assess whether Truvada-based PrEP can be an effective prevention tool in widespread use should definitely continue.