P-299. No Clinically Significant Drug-Drug Interactions Between Lenacapavir and Hormonal Contraceptives in PURPOSE 1

TL;DR

A study found that lenacapavir, an HIV prevention drug, does not significantly interact with hormonal contraceptives, meaning no dose adjustments are needed.

Contribution

The study provides new evidence that lenacapavir does not cause clinically significant drug interactions with common hormonal contraceptives.

Findings

LEN coadministration did not significantly alter the pharmacokinetics of progestin-type hormonal contraceptives.

Contraceptive levels remained stable over 26 weeks of follow-up in participants using LEN.

No significant impact of hormonal contraceptives on LEN pharmacokinetics was observed.

Abstract

Twice-yearly subcutaneous (SC) lenacapavir (LEN) demonstrated efficacy and safety for HIV pre-exposure prophylaxis (PrEP) in the Phase 3 randomized PURPOSE 1 (NCT04994509) trial in cisgender women. LEN is a CYP3A inhibitor and thus has the potential to increase concentrations of hormonal contraceptives metabolized by the CY3PA pathway. Therefore, we assessed drug–drug interactions between LEN and commonly used progestin-type long-acting (LA) hormonal contraceptives in PURPOSE 1 participants.

PURPOSE 1 participants were randomized 2:2:1 to SC LEN or oral F/TAF or F/TDF. Free contraception was provided but not required. We evaluated etonogestrel (ENG), medroxyprogesterone acetate (DMPA), and norethindrone enanthate (NET-EN) concentrations based on observed levels in a selected subset of participants in the LEN group taking these contraceptives at baseline (prior to dosing) through 26 weeks (Ws) of follow-up. Using a population pharmacokinetics (popPK) model, we assessed the impact of hormonal contraceptives on LEN concentrations. Adverse events (AEs) for relevant groups were assessed.

Of 2140 participants receiving LEN, 226 had uninterrupted LA hormonal contraceptive exposure through W26 (50 ENG, 121 DMPA, 55 NET-EN). Plasma concentrations of DMPA and NET-EN at W13 and W26 were comparable with baseline levels, irrespective of dose, frequency, or dosing changes across visits (Figure). Median ENG concentrations showed an upward trend at W13, before decreasing towards baseline levels at W26. Incidence of common ENG-related AEs was similar in the LEN and combined oral PrEP groups (headache, 11% vs 16%; heavy menstrual bleeding, 4% vs 5%). In the popPK analysis, no statistically significant impact of LA hormonal contraceptive use was observed on LEN PK.

LEN coadministration did not result in clinically significant changes in the PK of ENG, DMPA, and NET-EN progestin-type LA hormonal contraceptives, nor did these contraceptives impact LEN PK. Similar findings for LEN were observed with feminizing gender affirming hormonal therapy (Blumenthal et al, abstract submitted to IDWeek 2025). Taken together, these data suggest that no dose adjustments are needed when administering LEN with commonly used LA or oral hormonal contraceptives.

Disebo Potloane, MB, ChB, Dip. HIV Man, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Medical writing support Cheryl E. Louw, MB, ChB, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Medical writing support Godfrey Kigozi, MB, ChB, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Medical writing support Moelo Malahleha, MB, ChB, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Medical writing support William Brumskine, MB, ChB, Dip. HIV Man (SA), Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Grant/Research Support|Gilead Sciences, Inc.: Medical writing support Amy Ward, MBBCh, Dip. HIV Man, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Grant/Research Support|Gilead Sciences, Inc.: Medical writing support Dhayendre Moodley, PhD, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Medical writing support Alexander Kintu, MB, ChB, ScD, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Medical writing support and Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Marjorie Z. Imperial, PhD, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Medical writing support and Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Priyanka Arora, PhD, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Medical writing support and Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Renu Singh, PhD, MS, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: 1475-US-PSP, 1475-WO-PCT, 1474-US-PSP, 1515-US-PSP, 1515-WO-PCT|Gilead Sciences, Inc.: Medical writing support and Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Lillian B. Brown, MD, PhD, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Medical writing support and Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Christoph C. Carter, MD, PhD, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Medical writing support and Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Flavia Matovu Kiweewa, MB, ChB, MSc, PhD, Aspire Scientific: Medical writing support|Gilead Sciences, Inc.: Medical writing support

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