Federal health officials recommended Wednesday that hundreds of thousands of Americans at risk for AIDS take a daily pill that has been shown to prevent infection with the virus that causes it.

If broadly followed, the advice could transform AIDS prevention in the United States — from reliance on condoms, which may be effective but are unpopular with many men and women, to a regimen that relies on an antiretroviral drug.

It would mean a 50-fold increase in the number of prescriptions for the drug, Truvada — to 500,000 a year from fewer than 10,000. The drug costs $13,000 a year, and most insurers already cover it.

The guidelines tell doctors to consider the drug regimen, called PrEP, for pre-exposure prophylaxis, for gay men who have sex without condoms; heterosexuals with high-risk partners such as drug injectors or male bisexuals who have unprotected sex; patients who regularly have sex with anyone they know is infected; and anyone who shares needles or injects drugs.

Officials at the Centers for Disease Control and Prevention have long been frustrated that the number of H.I.V. infections in the United States has barely changed in a decade, stubbornly holding at 50,000 a year, despite 30 years of official advice to rely on condoms to block transmission.

Although there is no guarantee that gay men will adopt the drug regimen, federal officials say something must be done because condom use is going down. In a C.D.C. survey in November, the number of gay men reporting recent unprotected sex rose nearly 20 percent from 2005 to 2011.

Nevertheless, advocates for the drug regimen were elated at Wednesday’s announcement.

“This is wonderful,” said Damon L. Jacobs, a therapist in Manhattan who is HIV negative, has been on the regimen since 2011 and runs a Facebook page promoting it. “When an institution like the C.D.C. makes a statement, it makes a profound difference to the doctors who are ambivalent.”

Dr. Jonathan Mermin, director of the C.D.C.’s national center for AIDS and other sexually transmitted diseases, said the new guidelines should save many lives.

“On average, it takes a decade for a scientific breakthrough to be adopted,” he said. “We hope we can shorten that time frame and increase people’s survival.”

While many antiretroviral drugs could in theory be used for the drug regimen, the only pill approved for that purpose by the Food and Drug Administration is Truvada, made by Gilead Sciences.

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