Jean-Michel Molina1, Isabelle Charreau2, Bruno Spire3, Laurent Cotte4, Julie Chas5, Catherine Capitant2, Cecile Tremblay6, Daniela Rojas-Castro7, Eric Cua8, Armelle Pasquet9, Camille Bernaud10, Claire Pintado11, Constance Delaugerre12, Luis Sagaon-Teyssier3, Soizic Le Mestre13, Christian Chidiac4, Gilles Pialoux5, Diane Ponscarme11, Julien Fonsart11, David Thompson14, Mark A Wainberg15, Veronique Doré13, Laurence Meyer16. 1. Hôpital Saint-Louis, Départements de Maladies Infectieuses, Microbiologie, et Pharmacologie, Assistance Publique Hôpitaux de Paris, Paris, France; Université de Paris Diderot Paris 7, Sorbonne Paris Cité, Paris, France; INSERM UMR 941, Paris, France. Electronic address: jean-michel.molina@aphp.fr. 2. INSERM SC10 US19, Paris, France. 3. Aix-Marseille Université, INSERM UMR 912 SESSTIM, Marseille, France. 4. Hôpital de la Croix Rousse, Département des Maladies Infectieuses, Centre Hospitalier et Universitaire de Lyon, Lyon, France. 5. Hôpital Tenon, Département des Maladies Infectieuses, Paris, France. 6. Centre Hospitalier de l'Université de Montréal, Département de Microbiologie, Infectiologie, et Immunologie, Montreal, QC, Canada. 7. Association AIDES, Paris, France. 8. Hôpital de l'Archet, Département des Maladies Infectieuses, Nice, France. 9. Hôpital G Dron, Département des Maladies Infectieuses, Centre Hospitalier Universitaire de Tourcoing, Tourcoing, France. 10. Hôtel-Dieu, Département des Maladies Infectieuses, Nantes, France. 11. Hôpital Saint-Louis, Départements de Maladies Infectieuses, Microbiologie, et Pharmacologie, Assistance Publique Hôpitaux de Paris, Paris, France. 12. Hôpital Saint-Louis, Départements de Maladies Infectieuses, Microbiologie, et Pharmacologie, Assistance Publique Hôpitaux de Paris, Paris, France; Université de Paris Diderot Paris 7, Sorbonne Paris Cité, Paris, France; INSERM UMR 941, Paris, France. 13. ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), Paris, France. 14. Association Rezo, Montreal, QC, Canada. 15. McGill University AIDS Centre, Jewish General Hospital, Department of Microbiology and Immunology, Montreal, QC, Canada. 16. INSERM SC10 US19, Paris, France; Université Paris Sud, INSERM UMR 912 SESSTIM, Marseille, France.
Abstract
BACKGROUND: Data for on-demand pre-exposure prophylaxis (PrEP) are scarce. We implemented a cohort study to assess its efficacy, safety, and effect on sexual behaviour. METHODS: We invited men and transgender women who have sex with men, previously enrolled in the randomised placebo-controlled ANRS IPERGAY trial at seven sites (six in France and one in Canada), to participate in anopen-label extension with on-demand tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) to be taken before and after sexual intercourse. We assessed the incidence of HIV and other sexually transmitted infections (STIs), PrEP adherence, safety, and sexual behaviour. Statistical analyses included comparisons of proportions and incidence between the randomised phase of the ANRS IPERGAY trial and the open-label phase, and all participants were included in safety analyses. ANRS IPERGAY is registered with ClinicalTrials.gov, number NCT01473472. FINDINGS:Between Nov 4, 2014, and Jan 27, 2015, we enrolled 361 participants. Median follow-up was 18·4 months (IQR 17·7-19·1). One participant who discontinued PrEP acquired HIV infection. HIV incidence was 0·19 per 100 person-years (95% CI 0·01-1·08), compared with 6·60 per 100 person-years (3·60-11·05) in the placebo group of the randomised study, indicating a relative reduction of 97% (95% CI 81-100) in the incidence of HIV with on-demand PrEP. Participants used a median of 18 pills of study drugs per month (IQR 11-25), and at the 6 month visit 240 (71%) of 336 participants had tenofovir detected in plasma. Drug-related gastrointestinal events were reported in 49 participants (14%) but were self-limited. Only four participants (1%) discontinued PrEP, three because of an increase in plasma creatinine. The proportion of participants reporting condomless sex at their last receptive anal intercourse significantly increased from 77% (136 of 176 participants) at baseline to 86% (66 of 77 participants) at 18 months' follow-up (p for trend=0·0004). The incidence of a first bacterial STI during this open-label phase did not change significantly compared with the randomised phase (59·0 vs 49·1 per 100 person-years, respectively; p=0·11). INTERPRETATION: On-demand oral PrEP is highly effective at preventing HIV infection among high-risk men who have sex with men and therefore represents an alternative to daily PrEP, expanding choices for HIV prevention. High rates of STIs resulting from low condom use did not undermine PrEP efficacy, but warrant frequent testing. FUNDING: ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), the Canadian HIV Trials Network, Fonds Pierre Bergé-Sidaction, Gilead Sciences, and the Bill & Melinda Gates Foundation.
RCT Entities:
BACKGROUND: Data for on-demand pre-exposure prophylaxis (PrEP) are scarce. We implemented a cohort study to assess its efficacy, safety, and effect on sexual behaviour. METHODS: We invited men and transgender women who have sex with men, previously enrolled in the randomised placebo-controlled ANRS IPERGAY trial at seven sites (six in France and one in Canada), to participate in an open-label extension with on-demand tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) to be taken before and after sexual intercourse. We assessed the incidence of HIV and other sexually transmitted infections (STIs), PrEP adherence, safety, and sexual behaviour. Statistical analyses included comparisons of proportions and incidence between the randomised phase of the ANRS IPERGAY trial and the open-label phase, and all participants were included in safety analyses. ANRS IPERGAY is registered with ClinicalTrials.gov, number NCT01473472. FINDINGS: Between Nov 4, 2014, and Jan 27, 2015, we enrolled 361 participants. Median follow-up was 18·4 months (IQR 17·7-19·1). One participant who discontinued PrEP acquired HIV infection. HIV incidence was 0·19 per 100 person-years (95% CI 0·01-1·08), compared with 6·60 per 100 person-years (3·60-11·05) in the placebo group of the randomised study, indicating a relative reduction of 97% (95% CI 81-100) in the incidence of HIV with on-demand PrEP. Participants used a median of 18 pills of study drugs per month (IQR 11-25), and at the 6 month visit 240 (71%) of 336 participants had tenofovir detected in plasma. Drug-related gastrointestinal events were reported in 49 participants (14%) but were self-limited. Only four participants (1%) discontinued PrEP, three because of an increase in plasma creatinine. The proportion of participants reporting condomless sex at their last receptive anal intercourse significantly increased from 77% (136 of 176 participants) at baseline to 86% (66 of 77 participants) at 18 months' follow-up (p for trend=0·0004). The incidence of a first bacterial STI during this open-label phase did not change significantly compared with the randomised phase (59·0 vs 49·1 per 100 person-years, respectively; p=0·11). INTERPRETATION: On-demand oral PrEP is highly effective at preventing HIV infection among high-risk men who have sex with men and therefore represents an alternative to daily PrEP, expanding choices for HIV prevention. High rates of STIs resulting from low condom use did not undermine PrEP efficacy, but warrant frequent testing. FUNDING: ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), the Canadian HIV Trials Network, Fonds Pierre Bergé-Sidaction, Gilead Sciences, and the Bill & Melinda Gates Foundation.
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