CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

Oral Abstracts

119

Dolutegravir Does Not Reduce Levonorgestrel or Medroxyprogesterone Acetate Concentrations in WLWH Rebecca Ryan 1 , Bame Bame 1 , Aamirah Mussa 1 , Mbabi Bapabi 1 , Neo Moshashane 1 , Imogen Mechie 1 , Samuel Ensor 1 , Neo Ndlovu 1 , Laura J. Else 2 , Laura Dickinson 2 , Alieu Amara 2 , Andrew Davison 3 , Ava Avalos 1 , Saye Khoo 2 , Chelsea Morroni 1 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 University of Liverpool, Liverpool, UK, 3 Liverpool Clinical Laboratories, Liverpool, UK Background: Drug-drug interactions (DDIs) between contraceptives and antiretroviral therapy (ART) may increase the risk of unintended pregnancy and side effects. The levonorgestrel (LNG) implant and depot medroxyprogesterone acetate (DMPA) injectable are commonly used contraceptives in women living with HIV (WLWH), but pharmacokinetic (PK) data evaluating DDIs between dolutegravir (DTG) and LNG or MPA are lacking. Methods: We conducted a phase 4 non-randomised, parallel-arm, open-label PK study among non-pregnant WLWH on DTG-based ART and HIV-negative, ART-naïve women in Botswana, who chose to initiate the LNG implant or DMPA injectable (n=140; 70 LNG, 70 DMPA; 35 WLWH per arm). Blood was sampled before contraceptive initiation and at 2-4 weekly intervals. A pregnancy test and data on safety and tolerability were collected each visit. Area under the concentration-time curves of LNG over 24 weeks (LNG AUC 24weeks ) and MPA over 12 weeks (MPA AUC 12weeks ) were compared between WLWH on DTG-based ART and HIV-negative, ART-naïve women using geometric mean ratios (GMR). Results: Median (range) LNG AUC 24weeks was 13732 (6252-46797) pg.week/ mL and 10157 (3922-36311) pg.week/mL in WLWH on DTG-based ART and HIV-negative women respectively; GMR 1.30, 95% CI 0.99-1.68. Median (range) MPA AUC 12weeks was 10770 (4665-20005) pg.week/mL and 10212 (3018-18122) pg.week/mL in WLWH on DTG-based ART and HIV-negative women respectively; GMR 1.09, 95% CI 0.91-1.32. LNG C max was higher in WLWH on DTG compared to HIV-negative women (GMR 1.71, 95% CI 1.01-2.89), while MPA C max was similar between groups (GMR 1.16, 95% CI 0.92-1.47). There was no difference in median DTG concentrations before and after LNG (2155 vs. 2774pg/ml, p=0.09) or MPA (3358 vs. 3244pg/ml, p=0.46). Both contraceptive methods were well-tolerated, with no unintended pregnancies or serious adverse events. Endogenous progesterone was suppressed (<0.7 nmol/L) in 93% of WLWH on DTG vs. 78% HIV-negative women using LNG implant at 24 weeks, p=0.09; and 94% of WLWH on DTG vs. 87% HIV-negative women using DMPA injectable at 12 weeks, p=0.35. Conclusions: There are no clinically significant DDIs between DTG-based ART and the LNG implant or DMPA injectable. DTG does not reduce LNG or MPA concentrations; and the LNG implant and DMPA injectable do not reduce DTG levels in WLWH. The LNG implant and DMPA injectable are both highly effective, safe and well-tolerated contraceptive options for WLWH on DTG-based ART.

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Lenacapavir Pharmacokinetics, Safety, and Efficacy in Adolescents and Adults in PURPOSE 1 Katherine Gill 1 , Nkosiphile Ndlovu 2 , William Brumskine 3 , Manjeetha Jaggernath 4 , Zwalethu Zwane 5 , Yang Zhao 6 , John Ling 6 , Priyanka Arora 6 , Renu Singh 6 , Alexander Kintu 6 , Christoph Carter 6 , Moupali Das 6 , Disebo Potloane 7 1 Desmond Tutu HIV Foundation, Cape Town, South Africa, 2 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 3 The Aurum Institute NPC, Rustenburg, South Africa, 4 University of the Witwatersrand, Johannesburg, South Africa, 5 The Aurum Institute NPC, Pretoria, South Africa, 6 Gilead Sciences, Inc, Foster City, CA, USA, 7 University of KwaZulu-Natal, Durban, South Africa Background: Despite having high HIV incidence, adolescents have historically been excluded from Phase 3 HIV trials; separate trials of ~25–50 adolescents are required, resulting in prolonged delays in access to pre-exposure prophylaxis (PrEP). The PURPOSE program is the first to intentionally include adolescents aged 16 and 17 years. PURPOSE 1 found twice-yearly lenacapavir (LEN) was highly efficacious in people aged 16–25 years. We describe our approach to adolescent inclusion and a comparison of the pharmacokinetics (PK), safety, and efficacy of LEN in adolescents vs adults. Methods: The study team engaged with key stakeholders, such as adolescent medicine experts and community advocates, to ethically and responsibly include adolescents. Consistent with standard practice, most adolescents provided assent and parents/guardians provided consent for trial inclusion. Innovations for adolescent inclusion included a community consent process led by a site community advisory board, after which waivers for parental consent were issued and adolescents could consent for themselves at that site. In other locales, adolescents who had ever been pregnant were considered emancipated and could consent for themselves. Further, an independent data monitoring committee reviewed safety data from the first 300 adult participants prior to adolescent enrollment. We compared LEN PK at Weeks 4, 8, 13, 26, and every 13 weeks thereafter, adverse events (AEs), laboratory abnormalities, and HIV infections between adolescents and adults. Results: We enrolled 124 adolescents; 56 were assigned to the LEN group. Preliminary observed LEN plasma concentrations were comparable between adolescents and adults; LEN C trough at Week 26 is shown (Fig). In both adolescents and adults in the LEN group, the most common AEs (excluding injection-site reactions [ISRs]) were headache, genitourinary chlamydia, and urinary tract infection; the most common ISRs were low-grade nodules, pain, and swelling. Laboratory abnormalities were mostly low grade and similar between adolescents and adults. There were no incident HIV infections among adolescents or adults receiving LEN. Conclusions: LEN was safe and well-tolerated, with similar PK in adolescents aged 16 and 17 years versus adults, supporting extrapolation of efficacy in younger people. The intentional efforts to include adolescents resulted in robust enrollment ~2.5 to 5-fold higher than typical adolescent-dedicated studies, potentially accelerating access for adolescents who need or want PrEP.

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CROI 2025