Background:
Interim results of the ANRS Doxyvac trial (NCT04597424) have shown significant reductions in the incidence of chlamydia, syphilis and gonorrhea with doxycycline PEP and a significant reduction in the incidence of a first episode of gonorrhea with the 4CMenB vaccine, but not of cumulated gonorrhea episodes.
Methods:
MSM on PrEP with a history of STI, were randomized in an open-label factorial design trial to receive doxycycline PEP (200 mg within 72h of condomless sex) or no PEP (2:1); and 2 shots of the 4CMenB vaccine or no vaccine (1:1). Participants were tested centrally at baseline, every 3 months and when symptomatic for N. gonorrhoeae (GC) and C. trachomatis (CT) by PCR in throat, anus and urine with serologic tests for syphilis. The co-primary endpoints were: the incidence of first episode of CT or syphilis from baseline for Doxy PEP and the incidence of a first episode of GC from 3 months for the vaccine intervention, using an intent-to-treat analysis. We used Cox proportional hazard models to compare incidence between Doxy PEP and no PEP adjusted for vaccine intervention and vice versa. Following external evidence, a single interim analysis occurred in September 2022 at the request of the DSMB who recommended to stop the trial for efficacy. All participants were then invited to come back for a final visit which occurred up to February 28, 2023. Final results are presented.
Results:
Between January 19, 2021, and September 19, 2022, 556 MSM were randomized and 545 were analyzed. Median age: 40 years (IQR 34-48), median of 10 sexual partners in past 3 months. Median follow-up: 14 months. There was no interaction between the two prevention strategies for the primary endpoints. The incidence of a first episode of CT or syphilis was 8.8 per and 53.2 per 100 PY in the Doxy PEP and no PEP arms, respectively (aHR: 0.17; 95%CI: 0.12-0.26). The incidence of a first episode of GC was 45.5 and 68.4 per 100 PY in the Doxy PEP and no PEP arms, respectively (aHR: 0.67; 95%CI: 0.52-0.87). The incidence of a first episode of GC was 58.3 and 77.1 per 100 PY in the 4CMenB vaccine and no vaccine arms, respectively (aHR: 0.78; 95%CI: 0.60-1.01) and the incidence of cumulative episodes was 52.6 and 62.4 per 100 PY, respectively (aIRR: 0.84 (0.67-1.07). One drug-related SAE was reported (Erythema).
Conclusions:
Among MSM on PrEP, doxy PEP significantly reduced the incidence of CT and syphilis and to a lesser extent of GC. 4CMenB vaccine no longer showed a significant impact on the incidence of GC.