A study showing that a daily pill reduces HIV risk in gay men is reason for great hope. US agencies should waste no time in assessing the ability of Pre-Exposure Prophylaxis to slow the HIV/AIDS epidemic.
Data released today from the iPrEx study concluding that the daily use of an HIV antiretroviral medication can prevent new cases of HIV among gay and bisexual men and trans females represents the most promising development in HIV/AIDS since the introduction of triple combination drug therapy in 1996.
iPrEx evaluated the safety and efficacy of Truvada, a single pill combining two drugs, tenofovir (TDF) and emtricitabine (FTC) as part of a study package that included counseling to continue condom use, medication adherence counseling, regular HIV testing and monitoring of side effects. 2,499 participants came from the United States (San Francisco and Boston), Peru, Ecuador, Brazil, South Africa and. Trial subjects were at high risk for HIV infection based on self-reports of multiple sex partners, engagement in unsafe sex, history of sexually transmitted infections and high rates of alcohol use.
Thirty-four infections occurred among participants in the drug arm of iPrEx and sixty-six in participants in the placebo arm. Researchers calculated that, overall, TDF/FTC cut new HIV infections by 43.8 percent compared to placebo (95% CI 15.4-62.6%; p = 0.005). Adjusted for participants who adhered to medication 50 percent of the time or more, overall efficacy was 50.2 percent (95% CI 17.9-69.7%; p = 0.006). Importantly, increased adherence to TDF/FTC improved efficacy as well. Overall, participants reported increased condom use and decreased sexual partners. Some side effects, notably nausea, were experienced by participants receiving medication, but there were no major adverse events. Drug resistance did not occur among those who seroconverted and were quickly switched to triple combination treatment. But long-term safety of TDF/FTC among HIV-negative individuals and drug resistance merit additional study. A compete report of iPrEx findings can be seen at www.nejm.com.
Project Inform wants to thank and congratulate the 2,500 altruistic individuals who participated in the iPrEx trial, the researchers who conducted it, and the agencies that provided funding. The world is deeply indebted to each and every one of them for their contribution to controlling HIV/AIDS.
More than 20,000 men and women around the world are currently participating in additional PrEP efficacy trials, including heterosexual couples with one HIV-infected partner, women at high risk of HIV infection and injection drug users. These trials will provide much needed answers for how PrEP might work in different populations, against different routes of HIV transmission and in different geographic and cultural contexts. Additional PrEP trials testing efficacy of different drugs and less than daily dosing are also needed. (More information about ongoing PrEP trials is available at www.avac.org/prep.)
Project Inform's Advice to the Community About PrEP Use
As promising as the iPrEx results are, Project Inform strongly urges gay and bisexual men and trans females not to attempt PrEP on their own. We strongly discourage HIV-negative people from acquiring Truvada from HIV-positive people for PrEP, thus threatening the health of both individuals. We stress that iPrEx data are based on taking TDF/FTC daily along with participation in behavioral counseling, condom use, medication adherence counseling and clinical monitoring. There are no data whatsoever to suggest that using PrEP episodically or around the time of sex is at all effective.
HIV-negative gay and bisexual men and trans females at high risk for infection wishing to consider initiating PrEP at this time should only do so in consultation with and under supervision of a qualified physician. Conversely, physicians seeing individuals known to them to be at high risk for HIV infection should only offer PrEP if they can do it as part of the package of services described above. At the current time, insurance companies are unlikely to pay for Truvada for PrEP, the cost of which may be as high as $14,400 per year in the US. Public health care programs will not currently pay for Truvada for PrEP, and significant advocacy will be required to assure payment for this preventive intervention if and when it is fully implemented. Project Inform will be actively involved in that advocacy.
PrEP's Potential, and That of HIV Antiretrovirals, in Slowing the Spread of HIV
Gay and bisexual men continue to be severely and disproportionately impacted by the HIV/AIDS epidemic in the United States, accounting for 53 percent of the 56,300 new HIV infections each year. The rate of new HIV diagnoses among gay and bisexual men is more than 44 times that of other men. Most new HIV infections among black and Latino gay and bisexual men occur in those aged 13–29. PrEP therefore represents a long-awaited and extremely exciting opportunity to reduce the impact of HIV in this hard-hit community.
Project Inform eagerly awaits data from trials of PrEP in women, particularly women of color, who are also in great need of a prevention intervention that gives them the ability to prevent infections if their partners will not use condoms. We also eagerly await the results of trials with injection drug users.
Promising indicators of the role of ARVs in prevention place the world at a significant crossroads in the HIV/AIDS epidemic. Data show that individuals effectively treated for HIV are less likely to transmit the virus to their sex or injection drug using partners. (www.projectinform.org/pdf/tlc_caps.pdf) The CAPRISA study concluded that a vaginal gel containing the HIV antiretroviral TDF (tenofovir) prevented 39 percent of infections in a study of African women. (www.projectinform.org/news/2010/081310.shtml) Studies of a rectal microbicide for use in women and gay and bisexual men are also underway. With the release of iPrEx, the world has the opportunity, if advocates and policy makers seize upon it, to achieve progress against the epidemic unimaginable only a few years ago. This is particularly true for developing nations, where the cost of ARVs is substantially lower than in developed nations (as little as .40 per day). Although the world must proceed cautiously and thoughtfully in further assessing the effectiveness of ARV-based prevention, we must not delay.
Urgent Next Steps for PrEP
Based on the extremely hopeful iPrEx data, Project Inform believes that the US Centers for Disease Control & Prevention and National Institutes of Health should immediately move to fund demonstration projects that establish optimal strategies for delivering PrEP outside of existing clinical trials, including strategies for supporting maximum adherence to the PrEP regimen, the effectiveness of its delivery in real world settings, cost and cost-effectivness of this intervention. Gilead, its manufacturer, should pursue FDA approval for the use of Truvada for prevention, and discussions need to begin to make its use affordable.
We also hope that the results of iPrEx and CAPRISA ignite a movement among HIV-negative individuals demanding the delivery of effective and affordable biomedical prevention interventions.
Concerns About PrEP and Project Inform's View of Those Issues
We understand that there will be substantial concerns about PrEP in the US:
The cost of this intervention is potentially high, including the cost of Truvada, regular HIV testing and monitoring for side-effects, and counseling to encourage adherence to the drug and to ongoing condom or sterile syringe use. In developed nations, PrEP may only be shown to be cost-effective in individuals at highest risk for HIV infection. But just as we have fought to make sure that ARVs are available to HIV-positive people despite their high cost, we should fight for the protection of HIV-negative people despite the cost of PrEP.
Many HIV-positive people will be concerned that the cost of ARVs are part of PrEP threatens access to HIV treatment, particularly through the AIDS Drug Assistance Program. By law, ADAP cannot pay for medications for HIV-negative individuals and no HIV agency is likely to advocate that it should. Project Inform does not believe that HIV care and treatment funding should be pitted against HIV prevention funding. Both must be adequately financed. We believe that a key way to protect access to care and treatment for people who are currently HIV-positive is to prevent more people from becoming infected in the first place.
Many will be concerned that only those who can afford PrEP will have access to it, exacerbating already serious disparities in the epidemic. Project Inform believes that all people have a right to remain HIV-negative. If and when PrEP is ready for widespread implementation, we will advocate for its delivery to those groups epidemiology shows are most affected by HIV, as well as for equal access for individuals of all incomes, with an emphasis on low-income individuals.
Many will be concerned that PrEP threatens resources for behavioral prevention interventions. We believe that PrEP must be only one of a set of prevention interventions available to HIV-negative people, including behavioral counseling, mental health and substance abuse counseling, condoms, sterile syringes, microbicides, and vaccines. We also believe, however, that limited prevention funding should be directed to those interventions proven to be the most effective.
Many will be concerned that PrEP may result in a further deterioration in rates of condom and sterile syringe use by HIV-negative people. Thus far, studies do not show that "behavioral disinhibition" results from PrEP. But this possible effect has to be carefully studied and responded to so that it does not render this new intervention useless, or even counter-productive. However, due to its cost and intensity as a prevention intervention, it is critical that the gay male community continue to encourage condom use as the first line of defense against HIV, with PrEP being a strategy for high risk men.
Finally, many will oppose PrEP, even if proven to be capable of slowing the epidemic, believing that it encourages irresponsible risk-taking. Similar arguments were intense in the early years of availability of the birth control pill. The idea that a lifesaving prevention intervention should be denied to people is not without precedent, but it is immoral and unethical. It flies in the face of fiscal responsibility, as the cost of preventing a case of HIV, even if PrEP is costly, greatly outstrips the cost of a lifetime of HIV care and treatment. Additionally, federal, state and local budgets support without question huge costs for the prevention of many health conditions affecting the general public, including hypertension and heart disease. Declining to pay for PrEP, or any other effective form of biomedical HIV prevention, would be transparently hateful and discriminatory.
Additional Information on PrEP
On November 30, Project Inform will release a document prepared with advocacy partners further discussing thoughts and recommendations about the issues involved in implementing PrEP. That document will be available at www.projectinform.org. Additional resources regarding iPrEx and PrEP are available at www.globaliprex.net; www.preparesf.org; and www.avac.org.