Table 1 Selected characteristics of the studies included in the systematic review

Harrison 1979 [14]

N. gonorrhoeae

USA

1080 men from a US Navy ship after sexual exposure during 2 periods of leave in a port in East Asia randomized to either 200 mg minocycline or placebo after each sexual exposure, but maximum 200 mg per 18 hour period. 815 of these men were reinterviewed and had urethral samples taken at a single time point. MIC results available for 62 isolates of N. gonorrhoeae out of 81 incident N. gonorrhoeae infections.

200 mg minocycline after each sexual exposure (median time between sex and PEP 8 hours, range 30 min-36 hours)

Agar dilution with tetracycline. MICs of each isolate reported. Threshold for definition of tetracycline resistance not defined

Overall, 54% reduction in culture positive urethral gonorrhoea. No effect on infections with elevated minocycline MIC

Molina 2018 [3, 16]

N. gonorrhoeae, M. genitalium

France

232 MSM randomized 1:1 to doxycycline (200 mg) or no prophylaxis within 24 hours post each episode of condomless sex. Follow up was 10 months. NG tested for via quarterly NG PCR of the pharynx/rectum/urine. The primary analysis was mITT. The primary outcome was the occurrence of a first STI, defined as first episode of syphilis, chlamydia, or gonorrhoea infection. MIC results were provided for 9 isolates of N. gonorrhoeae out of 57 incident N. gonorrhoeae infections. Culture was only attempted in 28 of the infections.

200 mg doxycycline within 24 hours after condomless sex

Agar dilution with tetracycline. Resistance defined as ≥1 mg/L. Only proportion of resistant isolates were reported (MICs of each isolate were not reported)

Occurrence of a first STI was lower in the doxyPEP arm than in the placebo arm (HR 0.53). Doxycycline reduced the occurrence of a first episode of chlamydia (HR 0.3) and syphilis (HR 0.27). The effect on gonorrhoea was not significant.

Luetkemeyer 2023 [5, 11]

N. gonorrhoeae, commensal Neisseria species, S. aureus

USA

501 MSM and transgender women (327 in the PrEP cohort and 174 in the PLWH cohort), with a history of chlamydia, gonorrhoea or syphilis in the past 12 months were randomized 2:1 to doxycycline (200 mg) or placebo within 72 hours post each episode of condomless sex. Followed up quarterly for 12 months. NG tested for via quarterly NG PCR of the pharynx/rectum/urine. The primary analysis was mITT. The primary outcome was the incidence of at least one bacterial STI (gonorrhea, chlamydia, syphilis) each quarter. Tetracycline susceptibility data available for 29 isolates of N. gonorrhoeae out of 157 incident N. gonorrhoeae infections, for 162 isolates of S. aureus and for 178 isolates of commensal Neisseria spp.

200 mg doxycycline within 72 hours after condomless sex

Agar dilution with tetracycline. Resistance defined as ≥2 mg/L. Only proportion of resistant isolates were reported (MICs of each isolate were not reported)

Doxycycline reduced the incidence of at least one diagnosed STI (RR 0.34 in PrEP cohort and 0.38 PLWHIV), of gonorrhoea (RR 4.5/0.43 respectively), chlamydia (RR 0.12/0.26, respectively) and syphilis (0.13/0.23, respectively)