CROI 2024 Abstract eBook

Abstract eBook

Oral Abstracts

cells (PBMCs) with a target protection threshold set at 36 fmol/10 6 cells) were assessed throughout implant placement and 4 weeks post-removal. Results: Study participant median age was 26 years and 13% had a history of contraceptive implant use. Common ISRs (Figure1) were mostly mild (Grade 1) with scarring, hyperpigmentation, and induration, continuing for the duration of the study. In Group 2, Grade 3 ISRs, reported in two participants, resolved on implant removal. Early implant removal prior to 48 weeks occurred in 11 (37%) (10 active arm) in a median [IQR] of 19 [10-27] weeks post-insertion, mostly due to ISRs. Plasma TAF was detectable in 77% of samples from Group 2 participants in the active arm, with 100% and 50% detection 0.5 and 6 hours post insertion while median [IQR] TFV-DP concentrations were 3.9 [1.7-13.3] and 14.8 [6.0-29.1] fmol/million cells in women with 1 and 2 active implants respectively, with 15% of samples reaching or exceeding the target concentration Conclusion: In this first-in-human TAF implant trial, we found an expected safety profile, predominantly as insertion site reactions, but sub-optimal tolerability. Implant drug release rates did not reach targeted PBMC TFV-DP concentrations in most participants. Inserting additional implants or increasing release rates would need to be counter-balanced with the potential for increased side effects and reduced tolerability. Additional PK analyses are underway.

(HIV-1) infection in resource-rich settings. Additional evidence is required to determine the role of LA for treatment programs in Africa, where demographic factors, viral subtypes, prior treatment exposure, prevalence of pre-existing antiviral drug resistance and standardized approach to treatment delivery and monitoring differ. Methods: This ongoing phase 3b randomized, multicentre, open-label trial evaluates efficacy, safety, and tolerability of switching from oral antiretroviral therapy (ART) to LA. HIV-1 positive adults, stable on first-line ART (TDF +3TC/ FTC+EFV/NVP/DTG) with VL <50 copies/ml at screening were enrolled at 8 African sites. Main exclusion criteria were past virologic failure, pregnancy and HBV infection. Participants were randomized (1:1) to continue oral ART (OT group) or switch to cabotegravir (CAB) and rilpivirine (RPV) intramuscular injections every 8 weeks (LA group). VL was monitored every 24 weeks. Primary outcome was the proportion of participants with VL <50 copies/ml at week 48, by FDA snapshot algorithm (non-inferiority margin 10%). Confirmed virologic failure (CVF, secondary outcome) was defined as 2 consecutive VL ≥200 copies/ ml. Resistance testing was done retrospectively on archived DNA at baseline in all participants, and at CVF. Results: 512 participants were enrolled (median age 42y; 58% female; 92% on DTG-based ART; 74% with prior NNRTI exposure; 14% baseline archived RPV resistance mutations; 57% viral subtype A1; 21% baseline BMI ≥30kg/m 2 ). Four withdrew by week 48 (2 LA, 2 OT group). At 48 weeks, 248/255 (97.3%) in LA and 252/257 (98.1%) in OT group had VL<50 copies/mL (difference -0.8%; 95%CI -3.4 to 1.8%); demonstrating non-inferiority (Table). One participant in LA group met the definition of CVF. Adverse events of grade ≥3 severity occurred in 24 (9%) in LA and 10 (4%) in OT group; only one adverse event in LA led to treatment discontinuation (injection-site abscess).Treatment satisfaction increased after switching to long-acting therapy. Conclusion: At 48 weeks, CAB and RPV LA showed non-inferior efficacy to standard oral ART when used in the public health approach with sparse VL monitoring and where pre-existing RPV resistance, subtype A1 virus and obesity are common. CVF and acquired resistance was rare. LA was effective and safe and may be considered for use in treatment programs in sub-Saharan Africa. Phase I Safety, Tolerability and Pharmacokinetics of Tenofovir Alafenamide Implants in African Women Tanuja N Gengiah 1 , Quarraisha Abdool Karim 1 , Lara Lewis 1 , Ishana Harkoo 1 , Leila E. Mansoor 1 , Johara Khan 1 , Zainab Kharva 1 , Nqobile Myeni 1 , Natasha Samsunder 1 , Marc M. Baum 2 , John A. Moss 2 , Catherine Hankins 3 , Bruno Pozzetto 4 , James F. Rooney 5 , Salim S. Abdool Karim 1 1 Centre for the AIDS Programme of Research in South Africa, Durban, South Africa, 2 Oak Crest Institute of Science, Monrovia, CA, USA, 3 Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands, 4 Centre International de Recherche en Infectiologie, Saint-Etienne, France, 5 Gilead Sciences, Inc, Foster City, CA, USA Background: Long-acting antiretroviral formulations offer an innovative solution to support adherence in African women seeking HIV pre-exposure prophylaxis. Micro-tabletted tenofovir alafenamide (TAF), a potent antiretroviral drug with established systemic safety, was formulated in a silicone elastomer sub-dermal implant and tested for safety, tolerability, and pharmacokinetics (PK). Methods: Healthy, adult South African women at low HIV risk enrolled in the CAPRISA 018 Phase I trial. To assess initial safety, six women received a single TAF (110mg) implant with an estimated 0.25mg/day in vivo release rate for 4 weeks (Group 1). Thereafter, 30 women randomized 1:1 to either one or two TAF implants, assigned blinded in a 4:1 active (n=24) to placebo (n=6) ratio, for 48 weeks (Group 2). Implant safety (systemic and implant site reactions [ISRs]: frequency, severity grading, time to resolution), tolerability (scheduled vs early removals), and PK evaluations (TAF plasma concentrations, and active metabolite tenofovir diphosphate [TFV- DP] in peripheral blood mononuclear

Oral Abstracts

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Final Results of ANRS 174 D OXYVAC: A Randomized Trial to Prevent STI in MSM on PrEP Jean-Michel Molina 1 , Béatrice Berçot 1 , Lambert Assoumou 2 , Michele Algarte-Genin 2 , Emma Rubenstein 1 , Gilles Pialoux 2 , Christine Katlama 2 , Laure Surgers 2 , Cecile Bebear 3 , Nicolas Dupin 1 , Jean-Paul Viard 1 , Juliette Pavie 1 , Claudine Duvivier 1 , Jade Ghosn 1 , Dominique Costagliola 2 1 University of Paris Cité, Paris, France, 2 Sorbonne University, Paris, France, 3 University of Bordeaux, Bordeaux, France Background: Interim results of the ANRS Doxyvac trial (NCT04597424) have shown significant reductions in the incidence of chlamydia, syphilis and gonorrhea with doxycycline PEP and a significant reduction in the incidence of a first episode of gonorrhea with the 4CMenB vaccine, but not of cumulated gonorrhea episodes. Methods: MSM on PrEP with a history of STI, were randomized in an open label factorial design trial to receive doxycycline PEP (200 mg within 72h of condomless sex) or no PEP (2:1); and 2 shots of the 4CMenB vaccine or no vaccine (1:1). Participants were tested centrally at baseline, every 3 months and when symptomatic for N. gonorrhoeae (GC) and C. trachomatis (CT) by PCR in throat, anus and urine with serologic tests for syphilis. The co-primary endpoints were: the incidence of first episode of CT or syphilis from baseline for Doxy PEP and the incidence of a first episode of GC from 3 months for the vaccine intervention, using an intent-to-treat analysis. We used Cox proportional hazard models to compare incidence between Doxy PEP and no PEP adjusted for vaccine intervention and vice versa. Following external evidence, a single interim analysis occurred in September 2022 at the request of the DSMB who recommended to stop the trial for efficacy. All participants were then invited to come back for a final visit which occurred up to February 28, 2023. Final results are presented. Results: Between January 19, 2021, and September 19, 2022, 556 MSM were randomized and 545 were analyzed. Median age: 40 years (IQR 34-48), median

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CROI 2024