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The U.S. Public Health Service recently issued guidelines about the daily use of medication as preexposure prophylaxis (PrEP) to prevent HIV infection. The guidelines, based on randomized trials showing substantial reduction in HIV transmission among those receiving a daily combination of tenofovir and emtricitabine, suggest physicians offer PrEP to patients at high risk, including nonmonogamous men who have sex with men, serodiscordant couples (in both male-male and male-female relationships), heterosexual men and women in other risk groups (such as sex workers or those with recent sexually transmitted infection), and injection drug users. Here, 2 prominent HIV experts debate the use of PrEP in a 45-year-old man whose husband has HIV infection with an undetectable viral load on treatment. They discuss the patient's risk for HIV transmission from his husband and from other partners, the magnitude of the risk reduction he would gain with PrEP, and nonpharmacologic alternatives to reduce his likelihood of contracting HIV infection.