Postexposure doxycycline brings down STI rates among people on PrEP

Individuals already taking pre-exposure prophylaxis (PrEP) for HIV prevention saw sharp declines in chlamydia and syphilis cases, as well as a moderate reduction in urethral and rectal gonorrhoea, when they also took doxycycline after potential exposure (doxyPEP).

In a large cohort of people accessing HIV PrEP in an integrated healthcare system in northern California, quarterly chlamydia cases decreased from 9.6 percent to 2.0 percent after initiating doxyPEP (rate ratio [RR], 0.21, 95 percent confidence interval [CI], 0.16–0.27; p<0.001). Significant reductions were observed across all anatomical sites of infection, namely rectal (RR, 0.18, 95 percent CI, 0.13–0.24; p<0.001), pharyngeal (RR, 0.16, 95 percent CI, 0.09–0.31; p<0.001), and urethral (RR, 0.25, 95 percent CI, 0.16–0.40; p<0.001). [JAMA Intern Med 2025;doi:10.1001/jamainternmed.2024.7186]

DoxyPEP also reduced quarterly syphilis cases from 1.7 percent to 0.3 percent (RR, 0.20, 95 percent CI, 0.11–0.37; p<0.001) and quarterly gonorrhoea cases from 10.2 percent to 9.0 percent (RR, 0.88, 95 percent CI, 0.77–1.00; p=0.048). For site-specific gonorrhoea, significant declines were seen for rectal (RR, 0.81, 95 percent CI, 0.67–0.97; p=0.02) and urethral (RR, 0.56, 95 percent CI, 0.40–0.79; p=0.001) infections only.

In contrast, the incidence of sexually transmitted infections (STIs) remained stable in the post-doxyPEP implementation period among individuals not dispensed doxyPEP, the investigators noted. “By the end of the study period, chlamydia and syphilis positivity were lower among doxyPEP recipients than nonrecipients despite being higher among doxyPEP recipients than nonrecipients prior to doxyPEP implementation.”

They emphasized that the declines observed in quarterly STI positivity among individuals starting doxyPEP mirror those reported in two large randomized clinical trials. Cisgender gay and bisexual men and transgender women who were either living with HIV or using HIV PrEP saw the incidence decrease by 74 percent to 88 percent for chlamydia and by 73 percent to 87 percent for syphilis. [Lancet Infect Dis 2018;18:308-317; N Engl J Med 2023;388:1296-1306]

“These findings suggest that doxyPEP may offer substantial benefits for reducing population-level STI transmission with broader implementation,” the investigators said.

They, however, highlighted the importance of continued monitoring of STI testing and incidence among later doxyPEP adopters, those not engaged in HIV PrEP care, and over extended periods of doxyPEP use to evaluate and guide its implementation. Then, as the uptake of doxyPEP increases, constant evaluation for resistance in gonorrhoea and other infections, such as Staphylococcus aureus, becomes crucial.

The study included 11,551 HIV PrEP users (mean age 39.9 years, 95.1 percent male), of which 2,253 (19.5 percent) were dispensed doxyPEP. DoxyPEP recipients were mostly male (98.9 percent), and 48.6 percent had an STI in the year before starting the intervention. Compared with individuals not dispensed doxyPEP, doxyPEP recipients were older (mean age 40.4 vs 39.8 years; p=0.04), had used HIV PrEP longer (mean 4.2 vs 3.4 years; p<0.001), and were more likely to be commercially insured (92.8 percent vs 88.9 percent; p<0.001). Mean quarterly STI positivity was assessed from 24 months before to 12 months after starting doxyPEP.