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Despite continued reductions in the number of HIV cases reported among San Francisco men who have sex with men (MSM) and the HIV-prevention potential offered by pharmaceutical tools such as pre-exposure prophylaxis (PrEP), there are uncertainties, particularly given reported decreases in consistent condom use. A key uncertainty is what groups of MSM should be targeted. This study estimates the distribution of behavioral patterns before infection among San Francisco MSM newly infected with HIV in 2014.We used a novel modeling approach. The approach uses estimates from the National HIV Behavioral Surveillance System for MSM, the Medical Monitoring Project, 2 trials of PrEP, and a meta-analysis of per-act risks of HIV infection.The modeling study suggests that 76% of newly HIV-infected MSM in 2014 were individuals with no discernible strategy in the 6 months before infection: that is, they had condomless receptive anal intercourse with one or more partners not perceived to be HIV uninfected. An estimated 7% of newly infected MSM were serosorters before infection.Prevention efforts in San Francisco must reach HIV-uninfected MSM with no discernible behavioral strategy, a group that constitutes 8% of HIV-uninfected MSM in the city. Our study suggests that if all HIV-uninfected, San Francisco MSM with no discernible strategy had been on PrEP in 2014, there would have been 70% fewer HIV infections among San Francisco MSM. Uncertainty analysis suggests that PrEP's impact may be maximized by encouraging PrEP persistence and concomitant reductions in sexual risk behaviors.