U.S. health regulators last month approved Gilead Sciences Inc's Truvada -- already used globally to treat the human immunodeficiency virus -- for preventing the infection in healthy people at high risk of contracting the virus that causes AIDS.

A number of factors will limit the drug's use for preventing HIV, including the fact that in the United States many people most at risk of infection, as well as their sexual partners, do not have consistent access to healthcare. Even for those with coverage, insurance reimbursement for a $14,000-a-year drug is expected to be tricky.

In addition, therapy with the drug would require otherwise healthy young people to take a pill each day, plus show up for HIV testing every three months.

"There are a number of rather significant implementation challenges," said Dr. Stephen Morin, director of the Center for AIDS Prevention Studies at the University of California at San Francisco. "Part of it has to do with the requirement to take a pill a day, which could be addressed by a more long-term administration of the drug."

Scientists are exploring a variety of tactics for using AIDS drug formulations to prevent HIV infection, including long-acting injections, gels and vaginal rings.

About 50,000 new HIV infections are reported each year in the United States. The number of patients taking Truvada to prevent HIV will likely be "a lot less" than that, said Howard Jaffe, head of the Gilead Foundation and a member of the company's senior management since 1991.

Gilead declined to give its own sales estimate.

"We are not expecting a meaningful increase or uptick in Truvada use from it," Jaffe said, referring to the FDA prevention approval. "We do expect it to enter into the conversation with regard to certain high-risk populations."

He said use of Truvada to prevent HIV infection will likely be most important outside of the United States, as developing countries where AIDS remains an epidemic look for additional ways to curb transmission of the virus.

Gilead has deals, mainly with generic drugmakers in India, to produce low-cost versions of its drugs for use in sub-Saharan Africa and other developing regions.

Dr. Paul Volberding, director of the Center for AIDS Research at the University of California at San Francisco, says Truvada could become a valuable tool for "a small fraction of people" who understand they have a high risk of exposure -- mainly female sex workers whose clients won't use condoms and gay men who decide they are going to engage in riskier sex.

"There is an easy consensus now that somebody that is on treatment and fully suppressed has either zero, or close to it, risk of transmitting the virus," Volberding said.

He and others emphasized that wider testing for HIV -- and treatment of already infected patients -- are the keys to reducing HIV incidence.

Of the 1.2 million Americans estimated to be infected with human immunodeficiency virus, almost 20 percent of them do not know it, according to the U.S. Centers for Disease Control and Prevention .

A recent study by the CDC found that 41 percent of U.S. HIV patients are under continual care of a doctor and just 28 percent had the viral infection under control.

PREVENTION THROUGH PREP

The U.S. Food and Drug Administration in July approved Truvada for adults who do not have the virus but may engage in sexual activity with HIV-infected partners, a concept known as pre-exposure prophylaxis (PrEP). The approval was for use in combination with safer sex practices, such as condoms.

The drug, which combines two anti-HIV drugs in one pill, was already approved for use with other antiretroviral agents to treat patients 12 and older who are infected with the virus. Antiretrovirals are designed to block various steps in replication of the virus.

Critics, including the AIDS Healthcare Foundation, a non-profit provider of HIV/AIDS medical care, argue that Truvada was shown to be only partially effective in preventing HIV transmission, can cause side effects including kidney problems and may cause healthy people to become resistant to it.

No U.S. public money has been allocated for treating uninsured individuals who do not already have AIDS, and some doctors question the degree to which insured patients would be covered.

"I would find it very difficult for there to be a provision to support funding for such a program when we have (HIV-positive) patients on waiting lists," said Murray Penner, deputy executive director at the National Alliance of State and Territorial AIDS Directors, which represents public-health departments.

State AIDS Drug Assistance Programs (ADAPs), which provide HIV treatment to low-income and uninsured patients, had 9,000 people on waiting lists a year ago. That number fell to 700 in mid-August after emergency federal funding was released, although many recession-battered states have tightened income criteria, reducing the number of eligible patients.

ADAPs generally have a total of more than 200,000 people enrolled in them over the course of a year, Penner said.

A ROUNDING ERROR IN SALES TERMS

Gilead, like other drugmakers, sells its HIV pills to ADAP programs at a significant discount.

"When we talk to our physician consultants who target HIV patients, they say they are not going to use much of it (Truvada) for prevention," said Phil Nadeau, an analyst at Wall Street firm Cowen & Co.

Any use of Truvada for preventing HIV infection "seems to be a rounding error in our estimates for treating HIV," he said, projecting Gilead's 2012 sales from the drug at $3.1 billion.

RBC Capital Markets described the prevention indication as a "niche" opportunity for Gilead, while Morgan Stanley said it "looks like a modest opportunity but many questions remain."

The CDC has recommended since early 2011 that high-risk gay and bisexual men should use the drug to protect against HIV.

Large insurers such as UnitedHealth Group Inc, WellPoint Inc and Aetna Inc say they cover Truvada for prevention as well as treatment of HIV, but are still deciding whether to institute rules about authorization.

Doctors remain skeptical that insurers will pay for Truvada without complicated documentation showing why a patient is high-risk and whether PrEP is the best preventive measure.

"It's not quite clear to me whether or not I'm going to be prescribing it," said Dr. Mehri McKellar, an infectious disease expert at Duke University in North Carolina. She described one HIV-positive patient whose male partner had not been infected.

"They had read about PrEP, but they use condoms 100 percent of the time," she said. "This is not supposed to at all replace condom use. It's not clear whether we should be talking about PrEP."

(Additional reporting by Julie Steenhuysen; Editing by Michele Gershberg and Douglas Royalty)

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