What would it mean for the future of the epidemic if HIV-negative people could take a pill to prevent HIV infection? That may soon become a reality: on May 10th, an FDA advisory panel voted 19 to 3 to recommend approval of the HIV medication Truvada as a prevention tool for men who have sex with men. The panel also voted 19 to 2 to recommend it for any HIV-negative person who is in a relationship with a partner who has HIV.
The FDA usually follows its committees' recommendations, but is not required to do so. It initially said it would announce its decision on approval before June 15, but later extended the target date until September 14. The agency wants more time to look at the proposed medication guide, educational training, and the implementation system for the possible rollout of PrEP (pre-exposure prophylaxis). AIDS organizations nationwide are eager to hear the decision, since approval could transform the way we think about HIV prevention. In addition to condoms, safer sex education, and behavioral counseling, a new medical tool may soon be available.
HIV meds have long proved essential for helping people with HIV better manage the virus. The introduction of AZT in 1987 changed the course of the epidemic by prolonging lives and challenging the perception that AIDS was a death sentence. At the dose used back then, however, it was highly toxic and came with taxing side effects. The true breakthrough came in 1995 with the introduction of combination HIV therapy, a new approach to treatment that allowed HIV-positive people to lead healthier lives.
Recent research has presented a new use of HIV meds: the "treatment as prevention" model. One study found that people with HIV are 96% less likely to transmit HIV to their negative partners when they start taking HIV meds earlier. But the use of HIV meds to prevent transmission has largely been limited to HIV-positive people up to this point.
So it comes as a major development that the FDA is currently reviewing an application for use of the HIV med Truvada as a prevention tool. Several studies have found that HIV meds taken daily by HIV-negative people can reduce their chances of infection. Some doctors already prescribe HIV meds as prevention, but since the FDA does not allow drug companies to market HIV meds for prevention, these are known as "off-label" uses and are not covered by most insurance plans.
Over a million people live with HIV in the U.S., and an estimated 50,000 are newly infected each year. Recent studies focusing on HIV vaccines and microbicides (gels to prevent transmission) have produced disappointing results, and marginalized communities continue to bear the brunt of failed prevention efforts. People who are oppressed based on race, class, gender, and sexual orientation are at increasingly high risk for HIV, creating more complex challenges for prevention programs. Transmission rates among MSM are a particular area of concern. The CDC estimates that HIV infections among MSM increased by 34% between 2006 and 2009. They increased 48% among MSM of color during the same period. Thus, there is a sense of urgency among AIDS advocates that we need new prevention strategies.
Several studies have shown that PrEP is an effective prevention tool, including the "iPrEx" study, which was completed in November 2010 in Brazil, Ecuador, Peru, South Africa, Thailand, and the U.S. In this study, a total of 2,499 HIV-negative MSM and transgender women who have sex with men took either a daily Truvada pill or a placebo (sugar pill).
Researchers found that those taking Truvada were 44% less likely to become infected with HIV than those taking the placebo. Among participants who reported having unprotected receptive anal intercourse, which is higher risk for HIV, Truvada reduced infections by 58%.
PrEP could be most effective for people who have less control over condom use, such as sex workers or people who have sex under the influence of drugs and alcohol. Additionally, a married woman who has difficulty advocating for safer sex with her husband could use PrEP to protect herself if she suspects he has other partners. Researchers were unable to detect Truvada in the blood of the majority of study participants who took Truvada and became HIV positive.
This means they might not have been taking the drugs as directed. In fact, adherence was surprisingly low. While people claimed an average of 90% adherence, blood tests indicated an adherence rate closer to 50%. On one hand, this opens the possibility that PrEP could be even more effective than iPrEx showed. On the other hand, adherence rates present a serious hurdle. If people in a closely monitored study have difficulty taking a daily drug, how can people be expected to take meds consistently in the "real world"?
In July 2011, the University of Washington released early results for its Partners PrEP study, which provided Truvada, Viread, or a placebo to 4,758 serodiscordant (one partner HIV positive, the other not) couples in Kenya and Uganda. HIV meds were found to protect the HIV-negative partners in the study from infection. Those taking Truvada had 73% fewer infections, while those taking Viread had 62% fewer infections.
Unlike the iPrEx study, Partners PrEP had a remarkably high level of 95% adherence to the pills, which might explain the higher success rates. These findings suggest that PrEP is safe and effective for heterosexuals as well as MSM, and that serodiscordant couples might be a realistic target population for PrEP.
But these studies leave many questions unanswered. Given the short-term nature of PrEP studies, what long-term side effects can arise for people taking PrEP indefinitely? Could PrEP protect injection drug users, who have not been addressed in any of these studies? What would adherence to PrEP look like without regular monitoring and behavioral counseling? How might PrEP affect women who are pregnant or using hormonal birth control? How do social factors like race, income, culture, education, and nationality affect adherence rates? And how do we pay for it?
Some worry that PrEP would not be available to those who truly need it due to high price. There is no guarantee that Medicaid, Medicare, and private insurers would cover the cost of PrEP. Many people at risk for HIV are in low-income groups, and U.S. patent laws will block the availability of cheaper generic versions of PrEP.
Truvada can cost over $38 a day, while condoms cost under a dollar each. In meetings with clinicians and community advocates, Gilead has stated that the company has no plans to market Truvada for prevention. But if that changes, Gilead could make huge profits by marketing the drug not only to people with HIV, but to anyone at risk of being infected. PrEP might be available only for the wealthy, and not to those at highest risk of HIV infection. This would do little to address the social inequalities that make HIV prevention so complicated. And it would favor those who already have access to quality treatment while snubbing poorer people.
If funding is used to make PrEP more widely available, we face a challenge of how to use limited resources. Using the recently revised U.S. treatment guidelines that recommend HIV treatment for everyone with HIV, there are over 25 million people in the world who are in need of HIV meds but who do not have access to them. In the U.S. alone, over 3,500 people sit on waiting lists for HIV meds through the AIDS Drug Assistance Programs (ADAP). Can we justify investing in PrEP for HIV-negative people while the same drugs are unavailable to so many who need treatment? People with HIV in poor countries usually take cheaper generic versions of HIV meds, while people in the U.S. must pay more. A cynical cost-benefit analysis of Gilead's potential profits might encourage it to market PrEP in the U.S., rather than increase the accessibility of HIV meds all over the world.
A new study from Stanford University looked at the drug and health care costs of prescribing Truvada to MSM. Giving the drug to all MSM would cost $480 billion over 20 years, but targeting only those with five or more partners a year would bring that number down to $85 billion. Over the next two decades, they estimated 490,000 new infections in the U.S. if PrEP is not used. But even if it is only 44% effective, 41,000 new infections would be prevented if high-risk MSM took the drug. They conclude: "PrEP in the general MSM population could prevent a substantial number of HIV infections, but it is expensive. Use in high-risk MSM compares favorably with other interventions that are considered cost-effective but could result in annual PrEP expenditures of more than $4 billion."
"Even though it provides good value, it is still very expensive," said Jessie Juusola, lead author of the study. "In the current health-care climate, PrEP's costs may become prohibitive, especially given the other competing priorities for HIV resources, such as providing treatment for infected individuals."
Could a prevention pill prove harmful by giving people a false sense of safety? People might expect to be fully protected by PrEP and stop using more reliable forms of protection like condoms, which are inexpensive and 98% effective when used consistently and correctly. Though data from iPrEx and Partners PrEP are strong, they are not strong enough for advocates to consider PrEP a substitute for condoms. The appeal of a "magic pill" for HIV prevention might lure people looking for an excuse to stop using condoms.
More importantly, the iPrEx results show how difficult it was for people to take their pill every day, and how unrealistic it might be to ask a healthy, HIV-negative person to remember that without consistent support. Poor adherence threatens the long-term effectiveness of all HIV meds, with the virus more likely to build up resistance. Some MSM have reported buying HIV meds on the street and taking them only just before sex, thinking this will provide protection when there is no evidence to support that use. The illegal trade of HIV meds on the black market enables people to take them as PrEP without proper counseling, which can lead to drug-resistant strains. Without close monitoring, PrEP meds could enter the black market more easily and lead to more cases of improper use.
A few AIDS advocacy organizations have waged a campaign against PrEP approval, accusing the FDA of putting profits over safety. They claim that Gilead and the FDA have a close relationship and have worked to speed up the approval process. In early 2011, two Freedom of Information Act (FOIA) requests to obtain documents sent between Gilead and the FDA were filed, and the FDA denied both of them. There is concern that this could set a dangerous standard of pharmaceutical companies affecting public regulations.
Other AIDS advocacy groups argue that with the epidemic spreading at increasingly high rates among MSM, especially MSM of color, we cannot afford to dismiss PrEP as a potential tool. The CDC estimates that 53% of new HIV infections occur among MSM. Condoms, behavioral counseling, and social marketing have made a difference in some communities, but have not significantly slowed the spread of the epidemic in others. The rejection of any new strategy is a lost opportunity to prevent new infections.
High drug costs are real and devastating, but the dismissal of one request for FDA approval will not fix that problem. AIDS advocacy groups must work to reform drug patent laws so as to ensure the widest possible access to HIV drugs, notwithstanding opposition from drug companies. Cheaper HIV meds could save millions of lives, but wider availability of PrEP could save lives as well. Both approaches are compatible in a comprehensive approach to prevention. Following the FDA's approval of PrEP, AIDS advocates should pressure drug companies and state Medicaid programs to cover PrEP at discounted rates.
Regardless of how we pay for PrEP, we must carefully implement this new tool to preserve scarce resources and ensure that no one thinks of PrEP as a miracle pill for HIV prevention. Advocates and healthcare providers should focus on the groups most vulnerable to HIV, such as MSM and women of color, in particular sex workers, serodiscordant couples, and MSM who have unprotected anal sex with multiple partners. This focus would be the most cost-effective use of PrEP. We must also ensure that health care providers monitor treatment and maintain close communication with people taking PrEP to minimize side effects and fight drug resistance.
We should also not regard PrEP as a replacement for current methods of prevention. Its use must be combined with behavioral interventions to ensure that people practice safer sex and adhere to their drug regimen. Perhaps creative use of technology could increase adherence, like a text messaging reminder service.
In communities where PrEP is introduced, advocates must continue to combat social inequality. Poverty and incarceration, for example, present real obstacles to safer sex and drug adherence. Testing services should reach out to entire communities to ensure that people with HIV become aware of their status and receive counseling on the benefits of HIV treatment -- not only for their own health, but also to lower the risk of transmission. Health care providers need to focus on cultural competency with LGBT communities. This is particularly important for MSM and transgender women of color. Also, community organizations should address the potential stigma that might surround PrEP through counseling and social marketing.
Finally, clinical trials of PrEP should continue even if Truvada gains FDA approval, focusing on those most at risk. Injection drug users should be a priority, since no research is yet available on this group. Alternative forms of PrEP like injections, implants, and patches could address problems of adherence and should be studied.
PrEP could be a powerful tool in national and even global prevention efforts, but we are still far from a solution to the AIDS epidemic. AIDS advocates should support this new innovation, but hold institutions like the FDA and drug companies accountable if profit gets in the way of public health.
Liza Behrendt is a member of AVODAH: The Jewish Service Corps.