The latest study to show high efficacy of doxycycline post-exposure prophylaxis (Doxy PEP) in preventing sexually transmitted infections (STIs) among men who have sex with men (MSM) adds a new twist, showing — for the first time — reductions in gonorrhea among those receiving the meningococcal B vaccine.
“Among men who have sex with men on HIV PrEP, doxycycline PEP significantly reduced the incidence of chlamydia and syphilis and also had a significant impact on the incidence of gonorrhea,” said first author Jean-Michel Molina, MD, PhD, in presenting the findings at the Conference on Retroviruses and Opportunistic Infections (CROI) 2023.
In addition, “two doses of the meningococcal B vaccine reduced the incidence of a first episode of gonorrhea by roughly 50% among men who have sex with men,” said Molina, a professor of infectious diseases at the University of Paris, and head of the Infectious Diseases Department at the Saint-Louis and Lariboisière Hospitals in Paris, France.
Whereas the advent of PrEP has been associated with significant reductions in HIV transmission, rates of STIs have conversely been on the rise among MSM, specifically among those receiving PrEP.
Post-exposure prophylaxis with Doxy PEP has been shown to reduce the incidence of chlamydia and syphilis by approximately 70%; however, effects on prevention of gonorrhea have been less clear.
Meningococcal B vaccination has, meanwhile, shown intriguing reductions of gonorrhea incidence of as much as 26%–46% in some observational studies.
Therefore, Molina and colleagues decided to further investigate Doxy PEP as well as the meningococcal B vaccine in prevention of STIs.
For the ANRS 174 DOXYVAC trial, they enrolled 546 MSM in the open-label, multicenter study between January 2021 and July 2022.
The men were randomly assigned to one of 4 groups:
Doxycycline post-exposure prophylaxis (Doxy PEP: 200 mg; n = 332), or
No Doxy PEP (n = 170), or
Two shots of meningococcal B vaccine (4CMenB vaccine; n = 257), or
No 4CMenB vaccine (n = 245)
All participants were assigned to their groups within 72 hours of condomless sex.
The men, who had a median age of 39, had a median time of PrEP use of 42 months, a history of an STI in the past year, and their median number of sexual partners in the past 3 months was 10.
Their characteristics were well-balanced across the treatment groups. After discontinuations of 54 patients across the groups, the final analysis included 502 participants.
With a median follow-up of 9 months, the intent-to-treat analysis showed 13 subjects had a first episode of chlamydia or syphilis in the Doxy PEP group, vs 49 subjects infected in the no Doxy PEP arm, for an incidence of 5.6 vs 35.4 per 100 person-years, respectively (adjusted hazard ratio [HR], 0.16; P < .0001).
Infection specifically with chlamydia occurred among 21 men with no Doxy PEP vs 5 receiving Dox PEP (19.3 vs 2.1 per 100 person-years, respectively; HR, 0.11; P < .0001).
And infection with syphilis occurred in 18 men receiving no Doxy PEP vs 8 receiving the treatment (16.3 vs 3.4 per 100 person-years, respectively; HR, 0.21; P < .001).
The corresponding rates for gonorrhea infection were an incidence 41.3 vs 20.5 per 100 person-years, in the no Doxy PEP vs Doxy PEP arms, respectively; adjusted HR, 0.49; P = .001), and 29.4 vs 16.8 per 100 person-years for Mycoplasma genitalium infection; aHR, 0.55; P = .015).
Throughout the study, about 80% of patients in the Doxy PEP group reported using the prophylaxis treatment after their most recent sexual intercourse, with subjects reporting taking a median of seven pills per month.
Vaccine Effects in Preventing Gonorrhea “Highly Significant”
In the vaccine/no vaccine comparisons, 32 subjects in the no meningococcal vaccine group were infected with a first gonorrhea infection, compared with 17 in the vaccine group, representing an incidence of 19.7 vs 9.8 per 100 person-years, respectively (adjusted HR, 0.49; P = .016), which Molina called “highly significant.”
An analysis of the cumulative incidence of gonorrhea infection with the meningococcal vaccine showed rates in the no vaccine vs vaccine groups of 30.4 vs 20.1 per 100 person-years, respectively; however, statistical significance was not reached (aHR, 0.66; P = .052).
Importantly, there were no significant interactions in the results between those receiving Doxy PEP or the 4CMenB vaccine group, and there were no significant differences in drug-related serious adverse events between the groups.
Molina noted that the meningococcal B vaccine is known to contain key antigens that are shared between meningitis and gonorrhea, which could explain the benefits.
Although chlamydia and syphilis thus far appear to remain susceptible to Doxy PEP, resistances with gonorrhea remain a concern, hence the ability of the vaccine to provide some protection could be an added bonus.
“We know that [gonorrhea] is able to very quickly develop resistances to any antibiotics, so that was why we wanted to look beyond the antibiotic prophylaxis,” said Molina.
Among questions to explore looking ahead is the potential longevity of protection with the vaccine.
“We don’t know at this point how long the protection with the vaccine could last, or if [people] may need booster injections, for instance, but the literature suggests benefits for at least a year,” Molina said. “We are still monitoring the patients in the study to see what happens.”
He added that combination of the interventions may be of benefit.
“In the future, we think we may need to combine these approaches if we want to meet the WHO/UNAIDS targets to reduce the incidence of HIV and STIs by 90% by 2030.”
Commenting on the study, CROI vice-chair Landon Myer, MD, PhD, noted that “gonorrhea develops resistance quickly and can be hard to treat or prophylaxis, so the vaccine finding, which was hinted at by previous observational data, is really important.”
He agrees that “the duration of protective efficacy — a big thing in vaccines — is unknown.”
“Still, this is really significant,” Myer stressed. “An efficacious vaccine against a stubborn sexually transmitted infection.”
Conference on Retroviruses and Opportunistic Infections/CROI 2023: Abstract 170. Presented February 20, 2023.
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