Doxycycline prophylaxis and meningococcal group B vaccine to prevent bacterial sexually transmitted infections in France (ANRS 174 DOXYVAC): a multicentre, open-label, randomised trial with a 2 × 2 factorial design - 26/09/24
, Beatrice Bercot, ProfMD b, h, Lambert Assoumou, PhD d, Emma Rubenstein, MD a, Michele Algarte-Genin, PhD d, Gilles Pialoux, ProfMD e, Christine Katlama, ProfMD d, f, Laure Surgers, MD d, g, Cécile Bébéar, ProfMD h, Nicolas Dupin, ProfMD i, Moussa Ouattara, PhD d, Laurence Slama, MD j, Juliette Pavie, MD k, Claudine Duvivier, MD l, Benedicte Loze, BSc a, Lauriane Goldwirt, PharmD c, Severine Gibowski, PharmD n, Manon Ollivier, PharmD n, Jade Ghosn, ProfMD m, Dominique Costagliola, PhD dfor the
ANRS 174 DOXYVAC Study Group*
Summary |
Background |
Increased rates of sexually transmitted infections (STIs) are reported among men who have sex with men (MSM) and new interventions are needed. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of chlamydia or syphilis (or both) and whether the meningococcal group B vaccine (4CMenB) could reduce the incidence of gonorrhoea in this population.
Methods |
ANRS 174 DOXYVAC is a multicentre, open-label, randomised trial with a 2 × 2 factorial design conducted at ten hospital sites in Paris, France. Eligible participants were MSM aged 18 years or older, HIV negative, had a history of bacterial STIs within the 12 months before enrolment, and who were already included in the ANRS PREVENIR study (a cohort of MSM using pre-exposure prophylaxis with tenofovir and emtricitabine for HIV prevention). Participants were randomly assigned (2:1) to doxycycline PEP (two pills of 100 mg each orally within 72 h after condomless sex, with no more than three doses of 200 mg per week) or no PEP groups and were also randomly assigned (1:1) to the 4CMenB vaccine (GlaxoSmithKline, Paris, France; two intramuscular injections at enrolment and at 2 months) or no vaccine groups, using a computer-generated randomisation list with a permuted fixed block size of four. Follow-up occurred for at least 12 months (with visits every 3 months) up to 24 months. The coprimary outcomes were the risk of a first episode of chlamydia or syphilis (or both) after the enrolment visit at baseline for the doxycycline intervention and the risk of a first episode of gonorrhoea starting at month 3 (ie, 1 month after the second vaccine dose) for the vaccine intervention, analysed in the modified intention-to-treat population (defined as all randomly assigned participants who had at least one follow-up visit). This trial is registered with ClinicalTrials.gov, NCT04597424 (ongoing).
Findings |
Between Jan 19, 2021, and Sept 19, 2022, 556 participants were randomly assigned. 545 (98%) participants were included in the modified intention-to-treat analysis for the doxycycline PEP and no PEP groups and 544 (98%) were included for the 4CMenB vaccine and no vaccine groups. The median follow-up was 14 months (IQR 9–18). The median age was 40 years (34–48) and all 545 participants were male. There was no interaction between the two interventions (p≥0·1) for the primary outcome. The incidence of a first episode of chlamydia or syphilis (or both) was 8·8 per 100 person-years (35 events in 362 participants) in the doxycycline PEP group and 53·2 per 100 person-years (80 events in 183 participants) in the no PEP group (adjusted hazard ratio [aHR] 0·17 [95% CI 0·12–0·26]; p<0·0001). The incidence of a first episode of gonorrhoea, starting from month 3 was 58·3 per 100 person-years (103 events in 274 participants) in the 4CmenB vaccine group and 77·1 per 100 person-years (122 events in 270 participants) in the no vaccine group (aHR 0·78 [95% CI 0·60–1·01]; p=0·061). There were no deaths during the study. One drug-related serious adverse event (fixed-drug eruption) occurred in the doxycycline PEP group. Six (2%) participants in the doxycycline group discontinued doxycycline PEP because of gastrointestinal adverse events.
Interpretation |
Doxycycline PEP strongly reduced the incidence of chlamydia and syphilis in MSM, but we did not show efficacy of the 4CmenB vaccine for gonorrhoea. Doxycycline PEP should be assessed in other populations, such as heterosexual men and women, and its effect on antimicrobial resistance carefully monitored.
Funding |
ANRS Maladies Infectieuses Emergentes.
Translation |
For the French translation of the abstract see Supplementary Materials section.
Le texte complet de cet article est disponible en PDF.Plan
Vol 24 - N° 10
P. 1093-1104 - octobre 2024 Retour au numéro
Article précédent
- Switch to long-acting cabotegravir and rilpivirine in virologically suppressed adults with HIV in Africa (CARES): week 48 results from a randomised, multicentre, open-label, non-inferiority trial
- Cissy Kityo, Ivan K Mambule, Joseph Musaazi, Simiso Sokhela, Henry Mugerwa, Gilbert Ategeka, Fiona Cresswell, Abraham Siika, Josphat Kosgei, Reena Shah, Logashvari Naidoo, Kimton Opiyo, Caroline Otike, Karlien Möller, Arvind Kaimal, Charity Wambui, Veerle Van Eygen, Perry Mohammed, Fafa Addo Boateng, Nicholas I Paton, CARES trial team, Henry Mugerwa, William Tamale, Joshua Yiga, Susan Esther Asaasira, Nigel Kinyera, Christine Nambi, Dridah Luyirika Nakiboneka, Rose Kabatana, Winfred Kiyimba, Gilbert Ategeka, Ibrahim Yawe, Adolf Alinaitwe, Aidah Zawedde, George Wasswa, Allan Arinda, Angela Rweyora, Mary Goretti Kangah, Fiona Cresswell, Barbara Castelnuovo, Arvind Kaimal, Patience Ogwal, Neville Muhumuza, Max Okwero, Peruth Ayebare, Vivian Nakate, Jesca Asienzo, Hamza Mayanja, Eva Laker, Reena Shah, Felix Riunga, Peter Odhiambo Onyango, Josephine Wanja, Shaheen Sayed, Jaimini Gohil, Isaiah Mungathia, Alfred Mburu Githuka, Haron Kibwage, Abraham Mosigisi Siika, Charity Kanyoro Wambui, Viola Cherotich Kirui, Jairus Kipyego, Natalie Sang, Martha Mokeira Bisieri Mokaya, Consolata Chepkorir, Chris Sande Mboya, Ronald Tonui, Florence Njulu, Hilda Kaziga, Josphat Kosgei, Fredrick Sawe, Magdaline Adhiambo Omol, Faith Riziki, Ibrahim Daud, Leelgo Kimetto, Billy Omalla Okumu, Francis Lipuku, Simiso Sokhela, Francois Venter, Karlien Moller, Nompumelelo Nzuza, Gontse Ramela, Noxolo Tom, Tsitsi Nyamuzihwa, Philadelphia Macholo, Hlamulani Macebele, Godspower Akpomiemie, Logashvari Naidoo, Nitesha Jeenarain, Nivriti Hurbans, Mayuri Reddy, Gerald Thsepo Mphisa, Cissy Kityo, Nicholas Paton, Ivan Kiggundu Mambule, Kimton Opiyo, Joseph Musaazi, Caroline Otike, Ritah Kabanyoro, Francis Sekajja, Sandra Nantumbwe, Harriet Sekabira, Paul Ocitti, Benson Ouma, Immaculate Nankya, Pamela Ainembabazi, Melissa Lötter, Saeeda Mohamed, Madel Herbst, Tarryn Peters, Heena Mehta, Shaguftha Khan, Marlien Kruger, Willemijn van Rein-van der Horst, Fafa Addo Boateng, Rodica Van Solingen, Kati Vandermeulen, Veerle Van Eygen, Herta Crauwels, Donghan Luo, Donna Votto, Awhonukeh Idahosa, Fridah Mwendia, Lynne Klasko-Foster, Malavika Bondal, Ingrid Eshun-Wilsonova, Perry Mohammed, William Spreen, Ronald D’Amico, Pontiano Kaleebu, Sylvia Ojoo, Milly Katana, Yunus Moosa, Sam Phiri, Paula Munderi, Andrew Hill
- Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial
- Sarah E Silk, Wilmina F Kalinga, Jo Salkeld, Ivanny M Mtaka, Saumu Ahmed, Florence Milando, Ababacar Diouf, Caroline K Bundi, Neema Balige, Omar Hassan, Catherine G Mkindi, Stella Rwezaula, Thabit Athumani, Sarah Mswata, Nasoro S Lilolime, Beatus Simon, Hania Msami, Mohamed Mohamed, Damiano M David, Latipha Mohammed, Gloria Nyaulingo, Bakari Mwalimu, Omary Juma, Tunu G Mwamlima, Ibrahim A Sasamalo, Rose P Mkumbange, Janeth J Kamage, Jordan R Barrett, Lloyd D W King, Mimi M Hou, David Pulido, Cecilia Carnrot, Alison M Lawrie, Rachel E Cowan, Fay L Nugent, Rachel Roberts, Jee-Sun Cho, Carole A Long, Carolyn M Nielsen, Kazutoyo Miura, Simon J Draper, Ally I Olotu, Angela M Minassian
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?