The New Prevention Promise

A Study Shows Truvada Can Sharply Cut Risk of HIV Infection
by Larry Buhl

Just before Thanksgiving the results of a huge study showing that a well-established treatment for HIV could also be used for prevention gave many people reason to be thankful.

Nicknamed iPrEx, the double-blind study included nearly 2,500 men and was coordinated by the Gladstone Institutes of the University of California, San Francisco. The study found Truvada, a pill that combines two antiretroviral HIV medications, tenofovir and emtricitabine, curbed HIV infection in forty-four percent of its participants overall. The results were even better—around ninety percent effectiveness in preventing HIV infection—when the pill was taken on a strict daily regimen. The new approach to using Truvada, which has been used for several years to treat HIV, is called pre-exposure prophylaxis, or PrEP.

The Centers for Disease Control and Prevention (CDC) pointed out the study’s limitations, emphasizing that it looked only at gay men and Truvada. But the CDC says the approach might also prove effective among heterosexuals at high-risk for HIV and injection drug users, since the drug works by attacking the virus in the blood. “CDC, NIH, and other institutions are conducting trials around the world to determine the safety and effectiveness of PrEP for these populations; those results are expected within the next few years,” the CDC said in a prepared statement.

The results of the iPrEx study comes months after a similar study was reported at the International AIDS Conference in Vienna last summer. There, a trial that tested a vaginal microbicide gel containing one-percent tenofovir (the same drug in Gilead Sciences’ Viread) showed that South African women who applied the gel before and after sex had a thirty-nine percent lower risk of HIV infection than women who used an inactive placebo gel, reaching fifty-four percent for those who used it as directed most often.

Dr. Robert M. Grant, a virologist at the Gladstone Institutes in San Francisco and the study’s chief author, tells A&U that the information from iPrEx is consistent with another study presented for the first time in Vienna. “We now have two out of two studies showing [prophylaxis] can protect people.”

A game changer, not a silver bullet
The results of both studies give hope after nearly thirty years of frustration in biomedical prevention research. Countless HIV vaccine candidates have failed at early stages of testing. But Truvada is already available, while microbicide gel is made in only small amounts for clinical trials.

Experts say the results of the study are the best news in years. But Dr. Grant tells A&U that people must understand it is not a “cure” nor a vaccine.

“One key finding from the study is that those people who enrolled in our study protected themselves more, because they were counseled and tested and participated in [safer sex] support groups,” Grant says.

Dr. Grant and others associated with the trial say prophylaxis is for men who cannot use condoms consistently, including sex workers and those under pressure from partners or who lose their inhibitions when under the influence of drugs or alcohol.

Those who want to throw away the condoms should not be so hasty.

“This is a risk-reduction strategy for preventing HIV, but it’s not the silver bullet,” says Dr. Howard S. Jaffe, president of the Gilead Foundation, the philanthropic arm of Gilead Sciences, which makes Truvada.

“Condoms should remain the first line of defense in preventing HIV, but for those who can’t always use them, the pill provides a safety net,” Grant says.

Who pays?
A major question now is who will pay for the drug. In the United States, Truvada, made by Gilead Sciences, costs $12,000 to $14,000 a year. In the U.S., insurers and Medicare pay for the drugs, and the Ryan White Act covers the cost for the lowest income groups. But none of these payers yet have policies regarding supplying the drugs to uninfected people.

But whether and when the insurance industry in the U.S. might cover prophylaxis is an open question. “It will take a while for the CDC, FDA, and the insurance industry to discuss how best Truvada can be used,” Grant tells A&U. “But insurance does pay for preventive care in other instances, like lowering cholesterol, oral contraception, and smoking cessation. We think preventing HIV is a benefit for everyone, so I do think insurance should cover it.”

The results of this study will highlight the limits of resources, according to Dr. Jaffe. “If you put more money into prevention, where does it come from? The pie is not getting bigger.”

The problem of cost could be even larger around the world. It would cost tens of billions of dollars for prophylactic meds for the hundreds of millions of at-risk people worldwide, and in an era of tight foreign-aid budgets it is not clear who would pay for Truvada. In very poor countries, generic versions cost as little as forty cents a pill, but the money for that would still have to come from somewhere.

“A government in the developing world has x dollars for healthcare, so there will be a fierce debate when they have finite money yet want to spend more on prevention and prophylaxis,” Jaffe says.

Amid the PrEP enthusiasm it is easy to forget that there are a wide selection of prevention measures that already work. The problem with them, as it would be with Truvada or other prophylactic treatments, is access.

Underscoring the access issue is a new survey conducted by the Global Forum on MSM and HIV that found that a majority of men who have sex with men worldwide have trouble accessing basic prevention services such as HIV testing, counseling, and affordable condoms and lubricant.

Changing the dialogue about PrEP
Assuming Truvada will be widely accessible, there are many ways it could go wrong if there is no education or support, according to Dawn K. Smith, MD, biomedical interventions implementation officer in the Division of HIV/AIDS Prevention at the CDC. Smith tells A&U that several steps must be taken:
• Communication with at-risk groups about what PrEP will and won’t do and where to find PrEP.
• Training and guidelines for clinicians who will deliver PrEP.
• Monitoring and evaluation to ensure long range safety and effectiveness.

The FDA already approved Truvada for use in treating HIV, and in the U.S. any drug approved for one use can be prescribed for other uses. But while it’s already on the market, there will be a learning curve for using Truvada as prophylaxis.

“The trial showed Truvada worked best if you keep taking it, so what’s needed now for those who take it is adherence support,” Smith tells A&U. She added that there is the danger that those who use PrEP could increase risky behavior if they think they are protected by just taking a pill now and then.

“There is a good support and education network and testing [in relation to] AIDS medication right now, but that took a long time getting there,” she says. “We’ve been planning for the possibility of using a drug as a pre-exposure prophylactic for years, by consulting with clinical providers, users, and advocacy groups. But this result not only represents a change in policies but in messaging. We will be moving from a ‘practice safer sex’ message to a more complicated message.”

Larry Buhl is a freelance journalist and screenwriter living in Los Angeles.

January 2011