Antibiotic Taken Within 72 Hours of Sexual Exposure Reduces STIs by Two-Thirds


When taken within 3 days, doxycycline given post-exposure (doxy-PEP) decreased the incidence rates of syphilis, gonorrhea, and chlamydia significantly.

A new study demonstrated that the antibiotic, doxycycline, significantly prevented sexually transmitted infections (STIs) in men who have sex with men (MSM) and transgender women who took the medication within 72 hours of having condomless sex.

Specifically, the post-exposure approach, termed doxy-PEP, resulted in a two-thirds reduction in the incidence of syphilis, gonorrhea, and chlamydia among the study participants, all of whom reported having an STI within the previous year.

The study’s results were published in the New England Journal of Medicine. It was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

“This is an encouraging finding that could help reduce the number of sexually transmitted infections in populations most at-risk,” Hugh Auchincloss, MD, NIAID acting director, said in a statement.

Prevention remains a significant challenge especially in the face of increasing numbers. The incidence of STIs has been increasing in the US over the past few years with a disproportionate impact among MSM and transgender women. According to the CDC, an estimated 2.5 million cases of syphilis, gonorrhea, and chlamydia occurred in 2021, which is up from 2.4 million cases in 2020.

“Effective methods for preventing sexually transmitted infections are badly needed,” Auchincloss stated.

Investigators performed an open-label, randomized study using 2 cohorts and involving 501 participants. The first one had MSM and transgender women who were taking PrEP against HIV infection, with 327 participants known as the (PrEP cohort), and the other cohort had 173 participants living with HIV infection (persons living with HIV [PLWH) cohort) and who had gonorrhea, chlamydia, or syphilis in the past year.

Participants were randomly assigned in a 2:1 ratio to take 200 mg of doxycycline within 72 hours after condomless sex (doxycycline postexposure prophylaxis) or receive standard care without doxycycline. STI testing was performed quarterly. The primary end point was the incidence of at least one STI per follow-up quarter.

“In the PrEP cohort, an STI was diagnosed in 61 of 570 quarterly visits (10.7%) in the doxycycline group and 82 of 257 quarterly visits (31.9%) in the standard-care group, for an absolute difference of −21.2 percentage points and a relative risk of 0.34 (95% confidence interval [CI], 0.24 to 0.46; P<0.001),” the investigators wrote.

It is important to note the study’s findings did also reveal a slight increase in antibacterial resistance.

“Of the participants with gonorrhea culture available, tetracycline-resistant gonorrhea occurred in 5 of 13 in the doxycycline groups and 2 of 16 in the standard-care groups,” the authors wrote.

The investigators says this suggests that doxy-PEP may offer less protection against gonorrhea strains that are already tetracycline-resistant and that wider population-based surveillance for this type of resistance is important.

Additionally, the researchers found that doxy-PEP reduced Staphylococcus aureus—a bacteria commonly found on the skin “colonization”—by 50% after a year. However, in those who still had Staphylococcus aureus colonization at month 12, a modestly higher proportion of those in the doxy-PEP group had doxycycline resistance (16% vs 8%). This is important because doxycycline may be used to treat methicillin-resistant Staphylococcus aureus skin and soft tissue infections.

The investigators noted longer follow-up periods are needed to examine the potential antimicrobial resistance effect of intermittent doxy-PEP use. Doxy-PEP use in other populations disproportionately impacted by STIs, including women with HIV and those taking HIV PrEP, also deserve clinical study.

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