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DoxyPEP Cuts Chlamydia and Syphilis Incidence in MSM Using PrEP
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CROI 2024 (Conference on Retroviruses and Opportunistic Infections), March 3-6, 2024, Denver
Mark Mascolini
Doxycycline postexposure prophylaxis (DoxyPEP) significantly cut time to first chlamydia or syphilis infection in a randomized trial enrolling men who have sex with men (MSM) using HIV preexposure prophylaxis (PrEP) [1]. DoxyPEP proved less effective in preventing gonorrhea, and clinical relevance of the 4CMenB meningococcal vaccine seemed limited in preventing gonorrhea.
DoxyPEP lowered STI rates in two randomized trials enrolling MSM and transgender women living with HIV or using PrEP [2,3]. In observational studies, meningococcal B vaccines were associated with 26% to 46% lower gonorrhea incidence. At CROI Jean-Michel Molina reported final results of the ANRS 174 DOXYVAC trial, which tested DoxyPEP and the 4CMenB meningococcal vaccine in MSM using PrEP.
DOXYVAC randomized MSM on PrEP for more than 6 months and with bacterial STIs in the preceding 12 months to 200 mg of DoxyPEP 24 to 72 hours after sex or to no PEP. Men in each arm were further randomized to two 4CMenB vaccine injections at months 0 and 2 or to no vaccine. The researchers defined two primary efficacy endpoints: impact of DoxyPEP on time to first episode of syphilis or chlamydia, and impact of 4CMenB on time to first gonorrhea episode. In August 2022 the trial’s data and safety monitoring board (DSMB) called for an unblinded analysis that showed both interventions effective. As a result the DSMB recommended stopping enrollment of new participants and offering DoxyPEP and 4CMenB to all.
When the trial began, 362 men randomized to DoxyPEP, 183 randomized to no PEP, 274 randomized to 4CMenB, and 270 randomized to no vaccine were similar in median age (40 years overall), proportion of whites (88.4%), proportion born in France (83.3%), median months of PrEP (33), number of STIs in past 12 months (2), and number of condomless sex acts in the last 4 weeks (4).
After a median follow-up of 14 months, chlamydia or syphilis incidence was significantly lower in the DoxyPEP arm than in the no-PEP arm (8.8 vs 53.2 per 100 person-years) to yield almost an 80% lower adjusted hazard ratio (aHR) favoring DoxyPEP (aHR 0.17, 95% confidence interval [CI] 0.12 to 0.26, P < 0.0001).
Gonorrhea incidence proved significantly lower with DoxyPEP (45.5 per 100 person-years) than with no PEP (68.4 per 100 person-years) to yield a one-third lower rate with DoxyPEP (aHR 0.67, 95% CI 0.52 to 0.87, P < 0.003). But rates of high-level resistance to tetracycline given to prevent gonorrhea measured 35.5% in men taking DoxyPEP versus 12.5% in men not using PEP, a significant difference (P = 0.043).
Gonorrhea incidence proved lower in men who got the 4CMenB vaccine than in those who did not (58.3 versus 77.1 cases per 100 person-years), but adjusted analysis showed a trend toward an advantage—but not a significant advantage—for vaccination in preventing gonorrhea (aHR 0.78, 95% CI 0.60 to 1.01, P = 0.061). Analysis of first episodes of gonorrhea (either symptomatic or culture-positive) or cumulative incidence of gonorrhea (either symptomatic or culture-positive) did not come close to favoring 4CMenB over no vaccination. Drug-related adverse events proved substantially more frequent with 4CMenB than with DoxyPEP (48.0% vs 6.8%).
DOXYVAC researchers concluded that three large studies [1-3] now show that DoxyPEP strongly limits chlamydia and syphilis incidence in MSM and transgender women. The PEP strategy is less effecting in preventing gonorrhea, and high-level resistance to tetracyclines with DoxyPEP suggests its effectiveness against gonorrhea could dwindle with time.
Molina and colleagues judged data on the effectiveness of 4CMenB vaccination in preventing gonorrhea “inconclusive” and argued that the vaccine’s “clinical relevance seems very limited” because of similar rates of cumulative infections, symptomatic infections, and culture-positive infections with or without 4CMenB. An ongoing phase 3 trial of the vaccine could show whether these conclusions hold.
References
1. Molina J-MG, Bercot B, Assoumou L, et al. Final results of ANRS 174 DOXYVAC: a randomized trial to prevent STI in MSM on PrEP. CROI 2024 (Conference on Retroviruses and Opportunistic Infections), March 3-6, 2024, Denver. Abstract 124.
2. Molina JM, Charreau I, Chidiac C, et al, ANRS IPERGAY Study Group. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial. Lancet Infect Dis. 2018;18:308-317. doi: 10.1016/S1473-3099(17)30725-9. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30725-9/fulltext
3. Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure doxycycline to prevent bacterial sexually transmitted infections. N Engl J Med. 2023;388:1296-1306. doi: 10.1056/NEJMoa2211934. https://www.nejm.org/doi/10.1056/NEJMoa2211934
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