Combined Prevention of Sexually Transmitted Infections (STIs) in Men Who Have Sex With Men and Using Oral Tenofovir Disoproxil Fumarate/ Emtricitabine (TDF/FTC) for HIV Pre-Exposure Prophylaxis (PrEP)

Combined Prevention of Sexually Transmitted Infections (STIs) in Men Who Have Sex With Men and Using Oral Tenofovir Disoproxil Fumarate/ Emtricitabine (TDF/FTC) for HIV Pre-Exposure Prophylaxis (PrEP)

The study ANRS 174 Doxyvac is a clinical trial that will use Combined Prevention of Sexually Transmitted Infections (STIs) in Men Who Have Sex with Men and using oral TDF/FTC for HIV Pre-Exposure Prophylaxis (PrEP) and vaccination with Bexsero.

This is a randomized study with a factorial design for the 2 biomedical interventions (interventions 1 and 2).

Subjects will be randomized and assigned to two different interventions:

• Intervention 1: PEP with doxycycline or no PEP. Subjects will be randomized 2/1 to receive doxycycline PEP or no PEP
• Intervention 2: Meningococcal B vaccine (Bexsero®) or no vaccine Subjects will be randomized 1/1 to received 2 doses of Bexsero® vaccine (at the first visit and two months later) or no vaccine

Participants will be randomized in one of the following arms:

• Arm 1: doxycycline and Bexsero® vaccine (240 participants)
• Arm 2: doxycycline and no Bexsero® vaccine (240 participants)
• Arm 3: no doxycycline and Bexsero® vaccine (120 participants)
• Arm 4: no doxycycline and no Bexsero® vaccine (120 participants)

Randomization will be stratified by whether or not the participant enters in the ancillary study "intestinal microbiota".

Inclusion Criteria:

• Mens who have sex with mens (MSM) enrolled in the ANRS PREVENIR study.
• At least 6-month experience with PrEP (within the ANRS PREVENIR study or before starting the ANRS PREVENIR study).
• No clinical manifestation of primary HIV infection and no symptom of bacterial STI (chlamydia, gonorrhea, M. genitalium or syphilis).
• History of documented bacterial STI with at least one episode in the last 12 months.
• Participants who agree to sign the information and consent form specific to this study.
• Valid health insurance (State medical aid (AME) is not health insurance).

Exclusion Criteria:

• Syphilis diagnosed prior to inclusion without serologic evidence of cure (cure is defined as decreased by at least 4-fold of the non-treponemal antibody titer [Venereal Disease Research Laboratory (VDRL), Rapid Plasma Reagin (RPR)] relative to the titer at initiation of treatment of syphilis).
• HIV infection.
• Previous vaccination with Bexsero® or any other meningococcal B vaccine.
• Vaccination during the 4 weeks (28 days) preceding the first vaccination of the study.
• Previous vaccination with an experimental vaccine in the previous 5 years.
• Systemic treatment with retinoids : isotretinoin (Acnetrait®, Procuta®, Curacné®, Contracné®, …).
• Treatment with enzyme-inducing anticonvulsants (carbamazepine, phenobarbital, phenytoin, ….).
• Participant who has received immunoglobulins, a transfusion of blood or blood derivatives in the last 3 months.
• Known or suspected congenital or acquired immunodeficiency; immunosuppressive treatment in the last 6 months, such as cancer chemotherapy or radiotherapy; long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks in the last 3 months)
• Known allergy to antibiotics of the tetracycline family.
• Known allergy to any component of the Bexsero® vaccine.
• Known allergy to any component of the doxycycline pill.
• Known allergy to latex (contained in the vaccine cap).
• Thrombocytopenia or any other known coagulation disorder, which would be a contraindication to an intramuscular injection of Bexsero® vaccine.
• Documented oesophageal lesion
• Acute respiratory infection or severe acute febrile illness or systemic reaction that may present a significant risk if vaccinated in the month prior to inclusion.
• Any condition (clinical) that, in the investigator's opinion, would contraindicate intramuscular vaccination and blood sampling.
• Oral Anticoagulant treatment.
• Continuous treatment with doxycycline at inclusion.
• Vitamin A treatment in case of intake of 10 000 international unit or more.
• Participation in another research including an exclusion period still in progress at the time of inclusion.
• Under guardianship or curator, or deprived of liberty by a judicial or administrative decision.