The 30-year war on AIDS has produced its share of notable victories. In the U.S., behavioral changes and combination drug therapies brought down the AIDS-related death toll from a peak of nearly 52,000 in 1994 to about 14,600 in 2007, according to the Centers for Disease Control & Prevention. Yet HIV infections are still spreading rapidly in parts of Africa and Asia. And so far, efforts to find a cure or develop a vaccine that would stop HIV in its tracks have failed.
What if there were another way to slow the pandemic? Gilead Sciences is helping to test a different prevention strategy, which involves dosing individuals at risk of contracting AIDS with drugs normally used to treat people who are already infected. This approach, known as PrEP (pre-exposure prophylaxis), is being tested in 10 clinical trials involving more than 20,000 people in the U.S., Africa, Asia, and Latin America. Gilead has supplied many of the drugs for the trials. Other backers include the CDC, the National Institutes of Health, and the Bill & Melinda Gates Foundation. Researchers expect initial results in July.
If the data are positive, the approach could have a big impact on the AIDS pandemic—and on Gilead, says Leerink Swann analyst Josh Schimmer. He says PrEP could bring the Foster City (Calif.) company as much as $1 billion in sales in the U.S., where the number of infections among gay men has been rising since 1991, according to the CDC. Gilead pulled in $5.54 billion last year in sales of its top three AIDS drugs—Truvada, Atripla, and Viread—which are taken by 85% of U.S. patients as a first defense against the virus.
In the PrEP trials, Viread or Truvada is administered to uninfected people from groups most at risk of contracting the virus. The studies are also designed to determine whether those receiving the drugs take greater risks in the belief they're protected against the virus. Participants receive counseling on ways to avoid infection.
Speaking to a U.S. Senate committee about global health priorities on Mar. 10, Bill Gates said that, if the trials produce positive results, PrEP distribution programs could begin in developing countries in 2012. "PrEP is the next big thing," says Mitchell Warren, executive director of the New York-based AIDS Vaccine Advocacy Coalition. "We have a level of biological plausibility and early data in animal studies that is stronger than anything we have seen in the other approaches." A study presented last year at the Conference on Retroviruses and Opportunistic Infections (CROI) meeting in Montreal found Truvada cut the risk of infection almost sixteenfold in monkeys.
There are also precedents for such intervention. Drugs made by GlaxoSmithKline (GSK) and Boehringer Ingelheim are already used to prevent the virus from passing to babies in the wombs of infected mothers, and Glaxo's Combivir is prescribed to prevent infections in men who take it after unprotected sex with an HIV-positive partner. "I'm very hopeful that this approach will help to reduce HIV infection rates," says Dawn K. Smith, a researcher at the CDC who's devising plans to implement the strategy if it proves effective. "But I want to see the trial results before I call myself a believer."
The world needs new tools to fight AIDS, which is responsible for more deaths than any other infectious disease. About 33 million people live with HIV, according to UNAIDS, the coalition of U.N. agencies formed to fight it. In 2008, 2.7 million people were newly infected with the virus, and 2 million died from AIDS-related complications.
There could be downsides to PrEP. Gilead acknowledges that healthy patients who take AIDS drugs over the long term could experience side effects. And if the promise of protection from HIV appears to spur those at risk to take fewer precautions, the entire PrEP effort could suffer a black eye.
The prognosis for PrEP in sub-Saharan Africa is mixed. Skeptics worry it may be too costly on a continent where 22 million people are infected and per capita income is $951, according to the World Bank. Speaking at this year's CROI in San Francisco in February, Anthony Fauci, director of the U.S. National Institute of Allergy & Infectious Diseases, expressed confidence in PrEP's science but questioned the feasibility. "If we can't get 70% of the people who are infected in low- and middle-income countries on therapy, how are we going to get people who aren't even infected on therapy?" he asked.
In afflicted African countries, finding people best suited for PrEP will be difficult, since nearly everyone who's sexually active is at risk of HIV, says Francois Venter, president of the Southern African HIV Clinicians Society. "I have this horror that we'll have an effective intervention very few people are going to use," Venter says. "I worry that there hasn't been enough focus on who's going to take these drugs."
Even in wealthy nations cost will be a concern. Giving Truvada to 100,000 at-risk gay men in the U.S. would cost more than $1 billion a year, according to the CDC's Web site. That sum covers only the cost of the pills and doesn't include marketing, HIV testing, and doctors' visits, the agency says.
Assuming PrEP could prevent 50% of infections, it would almost halve the lifetime risk of catching HIV among high-risk gay men in the U.S.—and almost triple the lifetime treatment costs, according to a simulation published in Clinical Infectious Diseases in March 2009. PrEP is "unlikely to confer sufficient benefits to justify the current costs" of Truvada in the U.S., researchers from Yale University and Harvard Medical School concluded in the study. The model assumed a drug cost of $753 a month for each patient. The costs of PrEP could be lower if studies show smaller drug doses are equally effective at preventing infections, or if the pills could be taken less frequently, such as shortly before risky sex, instead of every day, said A. David Paltiel, the study's lead author.
Also uncertain is how PrEP might affect business for drugmakers. Gilead's director for clinical affairs, Jim Rooney, says he doesn't know what the commercial implications might be. "It's going to depend upon the data," he says, as well as how health officials evaluate the information and what clinical recommendations they make.
When the first anti-retroviral drugs were approved for treatment in the U.S. in 1987, critics complained they weren't affordable in poor nations, says the CDC's Smith. Now, more than 20 years later, about 40% of those infected worldwide are getting the drugs, according to UNAIDS. Says Smith: "If PrEP is highly efficacious, and if countries and UNAIDS and WHO and other public health agencies believe that it has a role to play in reducing new HIV infections, then we will find a way to make it available."