The finding contradicts some critics’ predictions that so-called pre-exposure prophylaxis, or PrEP, would lead to less condom use and more HIV infections.

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Demonstrating that taking a daily pill to prevent HIV infection works in the real world, San Francisco’s largest private health insurer said Wednesday that not one of its 657 clients receiving the drug had become infected over more than two years.

That outcome contradicts the prognostications of some critics who had predicted so-called pre-exposure prophylaxis, or PrEP, would lead to less condom use and more HIV infections.

A study published in Clinical Infectious Diseases found that the San Franciscans on PrEP, almost all of whom were gay men, did use fewer condoms — and contracted several other venereal diseases as a result. But none got HIV.

Most other sexual infections, while potentially dangerous, can be cured with antibiotics. HIV cannot, although it can be controlled with antiretroviral drugs taken for life.

“This is very reassuring data,” said Dr. Jonathan Volk, an epidemiologist for the insurer, Kaiser Permanente of San Francisco, and the study’s lead author. “It tells us that PrEP works even in a high-risk population.”

Observational studies like this one are not considered as scientifically rigorous as randomized clinical trials in which some participants receive a placebo. But Volk and his colleagues followed a large number of men engaged in very risky behavior from mid-2012, when the Food and Drug Administration (FDA) approved the use of a two-drug combination called Truvada for prevention of HIV infection, through February of this year. That amounts to 388 “person years” of observation.

By contrast, in a 2014 clinical trial among gay men in England, participants who received a placebo instead of Truvada had nine infections for every 100 person years of observation, said Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases.

That trial was one of several that were stopped early because researchers decided it was unethical to keep some participants on a placebo once it became clear that PrEP worked.

“This shows that the effectiveness of PrEP is really strikingly high,” Fauci said. “And this study takes it out of the realm of clinical trials and into the real world.”

The newest study “fills in a critical gap by showing that PrEP can prevent infections in a real-world public-health program,” said Mitchell Warren, executive director of AVAC, an organization lobbying for AIDS prevention.

About a third of all San Franciscans with private health insurance use Kaiser Permanente, which has its own hospitals, doctors and pharmacies and tracks all its patients in one electronic-records system.