Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study

Chas, Julie; Rojas-Castro, Daniela; Bernaud, C; Pintado, Claire; Sagaon-Teyssier, Luis; Ponscarme, Diane; Netzer, Emmanuelle; Lucas, Nicolás; Binesse, J; Foubert, V; Saouzanet, M; Euphrasie, F; Carette, Diane; Guillon, B; Saïdi, Yacine; Suzan, M; Cattin, G; Démoulin, Baptiste; Sagaon‐Teyssier, Luis; Lorente, Nicolas; Mestre, Soizic Le; Etien, N; Delfraissy, Jean‐François; Sas, J; Pankovitch, J; Klein, Marina B.; Anis, Aslam H.; Molina, Jean‐Michel; Wainberg, Mark A.; Trottier, Benôit; Tremblay, Cécile; Baril, Jean‐Guy; Pialoux, Gilles; Cotte, Laurent; Chéret, Antoine; Pasquet, A.; Cua, Éric; Besnier, Michel; Rozenbaum, Willy; Chidiac, Christian; Delaugerre, Constance; Bajos, Nathalie; Timsit, Julie; Peytavin, Gilles; Fonsart, Julien; Durand‐Zaleski, Isabelle; Meyer, Laurence; Aboulker, J; Spire, Bruno; Suzan‐Monti, Marie; Girard, Gabriel; Castro, Daniela Rojas; Préau, Marie; Morin, Michel; Thompson, David R.; Capitant, Catherine; Mennecier, Anaïs; Choucair, Elias; Doré, Véronique; Simon, Marie‐Christine; Charreau, Isabelle; Otis, Joanne; Lert, France; Diallo, Alpha; Gibowski, Séverine; Rabian, Cécile

doi:10.1016/s2352-3018(17)30089-9

Cited by 392 publications

(325 citation statements)

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“…This phenomenon may explain why no significant difference in eGFR decline was seen in our study between “low PrEP users” and other participants. It is also important to underline that the intermittent exposure to TDF/FTC with on‐demand PrEP was associated with a strong reduction in the relative risk of HIV infection, up to 97% with a median number of 18 pills per month . These data suggest that on‐demand PrEP may maximize the renal safety of TDF while providing a high level of protection against HIV.…”

Section: Discussionmentioning

confidence: 98%

Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate – emtricitabine for HIV pre‐exposure prophylaxis

et al. 2020

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Introduction Daily pre‐exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is associated with a small but statistically significant decrease in estimated glomerular filtration rate (eGFR). We assessed the renal safety of on‐demand PrEP with TDF/FTC in HIV‐1 uninfected men. Methods We used data from the randomized double‐blind placebo‐controlled ANRS‐IPERGAY trial and its open‐label extension conducted between February 2012 and June 2016 among HIV‐uninfected MSM starting on‐demand PrEP. Using linear mixed model, we evaluated the mean eGFR decline from baseline over time and determined risks factors associated with eGFR decline during the study. Results During the blind phase, with a median follow‐up of 9.4 months, the mean decline slope of eGFR from baseline was −0.88 and −1.53 mL/min/1.73 m2 per year in the placebo (n = 201) and the TDF/FTC group (n = 198) respectively, with a slope difference of 0.65 mL/min/1.73 m2 per year (p = 0.27). Including both phases, 389 participants started on‐demand TDF/FTC with a median follow‐up of 19.2 months and a mean decline of eGFR from baseline of −1.14 mL/min/1.73 m2 per year (p < 0.001). The slope of eGFR reduction was not significantly different in participants with baseline eGFR ≤ 90 mL/min/1.73 m2 (p = 0.44), age >40 years (p = 0.24) or hypertension (p = 0.21). There was a dose‐response relationship between recent tenofovir exposure and lower eGFR when considering the number of pills taken in the two months prior the visit (eGFR difference of −0.88 mL/min/1.73 m2 between >15 pills/month vs. ≤15 pills/month, p < 0.01) or plasma tenofovir concentrations at the visit (eGFR difference compared to ≤2 ng/mL: >2 to ≤10ng/mL: −0.98 mL/min/1.73 m2, >10 to ≤40ng/mL: −1.28 mL/min/1.73 m2, >40 ng/mL: −1.82 mL/min/1.73 m2, p < 0.001). Three participants discontinued TDF/FTC for eGFR < 60 mL/min/1.73 m2 during the OLE phase. No case of Fanconi syndrome was reported. Conclusions The renal safety of on‐demand PrEP with TDF/FTC was good. The overall reduction and intermittent exposure to TDF/FTC may explain this good renal safety.

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Section: Discussionmentioning

confidence: 98%

Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate – emtricitabine for HIV pre‐exposure prophylaxis

et al. 2020

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“…In HPTN 066, which reported combined results for CGM and cisgender women not on GAHT, the median (IQR) steady‐state TFV and FTC serum concentrations were 52 ng/mL (49 to 56) and 71 ng/mL (68 to 82) respectively . The iPrEx study demonstrated highly effective oral TDF/FTC as PrEP with only four doses per week, motivating the Ipergay and Prevenir on demand 2‐1‐1 TDF/FTC regimens, which demonstrated very high 86% and 100% HIV protection respectively, in MSM and TGW . However, there were too few TGW in those studies to draw conclusions regarding PrEP effectiveness on GAHT.…”

Section: Discussionmentioning

confidence: 99%

Transgender women on oral HIV pre‐exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men

et al. 2019

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Introduction Oral HIV Pre‐Exposure Prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective. Transgender women (TGW) have increased HIV risk, but have been underrepresented in trials. For TGW on oestrogens for gender‐affirming hormone treatment (GAHT), TDF/FTC‐oestrogen interactions may negatively affect HIV prevention or gender‐affirming goals. Our aim was to evaluate any pharmacokinetic drug‐drug interaction between GAHT and TDF/FTC. Methods We performed a pharmacokinetic study, in an urban outpatient setting in 2016 to 2018, of the effects of GAHT on TFV, FTC and the active forms TFV diphosphate (TFV‐DP) and FTC triphosphate (FTC‐TP) in eight TGW and eight cisgender men (CGM). At screening, participants were HIV negative. TGW were to maintain their GAHT regimens and have plasma oestradiol concentrations >100 pg/mL. Under direct observation, participants took oral TDF/FTC daily for seven days. At the last dose, blood was collected pre‐dose, one, two, four, six, eight and twenty‐four hours, and colon biopsies were collected at 24 hours to measure drug concentration. TGW versus CGM concentration comparisons used non‐parametric tests. Blood and colon tissue were also obtained to assess kinase expression. Results Plasma TFV and FTC C24 (trough) concentrations in TGW were lower by 32% (p = 0.010) and 32% (p = 0.038) respectively, when compared to CGM. Plasma TFV and FTC 24‐hr area under the concentration‐time curve in TGW trended toward and was significantly lower by 27% (p = 0.065) and 24% (p = 0.028) respectively. Peak plasma TFV and FTC concentrations, as well as all other pharmacokinetic measures, were not statistically significant when comparing TGW to CGM. Oestradiol concentrations were not different comparing before and after TDF/FTC dosing. Plasma oestrogen concentration, renal function (estimated creatinine clearance and glomerular filtration rate), and TFV and FTC plasma concentrations (trough and area under the concentration‐time curve) were all correlated. Conclusions GAHT modestly reduces both TFV and FTC plasma concentrations. In TGW taking GAHT, it is unknown if this reduction will impact the HIV protective efficacy of a daily PrEP regimen. However, the combination of an on demand (2 + 1 + 1) PrEP regimen and GAHT may result in concentrations too low for reliable prevention of HIV infection.

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“…131,132 An analysis of MSM having infrequent sexual intercourse in the IPERGAY study and subsequent open-label extension studies found high levels of efficacy, including in a subgroup who took an average of 2 or 3 doses of TDF/emtricitabine per week. 133,134 Clinical experience with on-demand PrEP confirmed efficacy of this dosing among MSM. 135,136 The 2–1-1 regimen achieved target exposures of tenofovir diphosphate and emtricitabine triphosphate in colorectal tissue at the time of coitus in 81% and 98% of the population when administered 2 and 24 hours before coitus, respectively; target exposure was sustained for the next10days.…”

Section: Preventionmentioning

confidence: 95%

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Saag

Benson

Gandhi

et al. 2018

JAMA

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IMPORTANCE Antiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection. OBJECTIVE To evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk. EVIDENCE REVIEW New evidence collected since the International Antiviral Society–USA 2016 recommendations via monthly PubMed and EMBASE literature searches up to April 2018; data presented at peer-reviewed scientific conferences. A volunteer panel of experts in HIV research and patient care considered these data and updated previous recommendations. FINDINGS ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV. CONCLUSIONS AND RELEVANCE Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.

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Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study

Abstract: 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.

Cited by 392 publications

References 22 publications

Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate – emtricitabine for HIV pre‐exposure prophylaxis

Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate – emtricitabine for HIV pre‐exposure prophylaxis

Transgender women on oral HIV pre‐exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

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