Final results of the ANRS DOXYVAC STI prevention trial

The ANRS DOXYVAC trial has two objectives: to assess the efficacy of a meningococcal B vaccine in reducing the risk of gonococcal infection, and to evaluate the efficacy of doxycycline as a post-exposure prophylaxis against sexually transmitted bacterial infections, when this antibiotic is taken within 24 to 72 hours of sexual intercourse.

Between January 2021 and September 2022, 556 volunteer men who have sex with men (MSM) living in the Paris region were randomly divided into four groups: one receiving post-exposure prophylaxis with doxycycline to be taken within 72 h of unprotected sex with a condom, another receiving pre-exposure vaccination with Bexsero®, the third receiving a combination of these two interventions, and the last receiving neither.

The results of an interim analysis were presented at the CROI in February 2023. They showed the efficacy of post-exposure doxycycline in reducing the occurrence of chlamydial infections, syphilis and, to a lesser extent, gonococcal infections. They also demonstrated the efficacy of Bexsero® vaccination in reducing the risk of gonococcal infections.

However, in 2023, a second analysis of the data carried out by the methodology and management center (CMG) showed results discordant with those of the intermediate analysis. This discrepancy concerned the effect of the meningococcal B vaccine on gonococcal infections. To better understand the reasons for this, the ANRS Emerging Infectious Diseases and the coordinating investigator, Prof. Jean-Michel Molina (Université Paris Cité and the Infectious Diseases Department of Hôpital Saint-Louis and Hôpital Lariboisière, AP-HP) set up an independent audit of the trial, accompanied by a new analysis of the results, both by the CMG and by an independent body. This audit revealed that the discrepancy was due to the omission of a data file at the time of analysis, which therefore failed to take into account a number of infections.

Following these analyses, the final results of the ANRS DOXYVAC trial show:

• Results consistent with the interim analysis concerning the efficacy of post-exposure doxycycline in reducing the occurrence of chlamydial infections, syphilis and, to a lesser extent, gonococcal infections. In fact, the risk of chlamydial infection or syphilis was reduced by 83% in the group receiving post-exposure doxycycline versus those not receiving it. Respectively, the risk of gonococcal infection was reduced by 33% in the doxycycline-treated group versus the non-treated group.
• Contrary to what was initially observed in the interim analysis, the meningococcal B vaccine did not show conclusive effects in preventing gonococcal infections.
• The occurrence of a severe adverse event (erythema[2]) linked to these two interventions in one of the 556 participants.

The final results of the ANRS 174 DOXYVAC trial have just been published in The Lancet Infectious Diseases on 23 May 2024.

[2] Congestive redness of the skin or mucous membranes that disappears with pressure

Reference

1.Molina JM (1), Bercot B (2,3), Assoumou l (4), Rubenstein E (1), Algarte-Genin M (4), Pialoux G (5), Katlama C (4,6), Surgers L (4,7), Bébéar C (3), Dupin N (8), Ouattara M (4), Slama L (9), Pavie J (10), Duvivier C (11), Loze B (1), Goldwirt L (12), Gibowski S (13), Ollivier M (13), Ghosn J (14), Costagliola D (4), for the ANRS 174 DOXYVAC Study Group. Doxycycline prophylaxis and meningococcal group B vaccine to prevent bacterial sexually transmitted infections in France (ANRS 174 DOXYVAC): multicentre, open-label, randomised trial with a 2 × 2 factorial design. Lancet Infect Dis 2024. Published Online May 23, 2024 https://doi.org/10.1016/ S1473-3099(24)00236-6

1. Department of Infectious Diseases, Hospital Saint-Louis, Hospital Lariboisière, INSERM U944, Assistance Publique Hôpitaux de Paris, University of Paris Cité, Paris, France
2. Laboratory of Microbiology, Hospital Saint-Louis, Hospital Lariboisière, INSERM U944, Assistance Publique Hôpitaux de Paris, University of Paris Cité, Paris, France
3. Department of Bacteriology, UMR CNRS 5234, French National Center for Bacterial Sexually Transmitted Infections, Bordeaux, France
4. Sorbonne University, INSERM, Institut Pierre Louis d’Epidemiology et de Santé Publique, Paris, France
5. Department of Infectious Diseases, Hôpital Tenon, Paris, France
6. Department of Infectious Diseases, Hospital of la Pitié- Salpétrière, Paris, France
7. Department of Infectious Diseases, Hospital Saint- Antoine, Sorbonne Université, Paris, France
8. Department of Dermatology, Hospital Cochin, Paris, France
9. Department of Immunology and Infectious Diseases, Hotel-Dieu, Paris, France
10. Department of Clinical Immunology, Hotel-Dieu, Paris, France
11. Department of Infectious Diseases, INSERM U1016, Necker Pasteur Infectiology Center, Paris, France
12. Department of Pharmacology, Hospital Saint-Louis, Hospital Lariboisière, INSERM U944, Assistance Publique Hôpitaux de Paris, University of Paris Cité, Paris, France
13. ANRS Maladies Infectieuses Emergentes, Paris, France
14. Department of Infectious Diseases, IAME UMR1137, Hospital Bichat, University of Paris Cité, Paris, France