Abstract
This case report describes the first documented use of lenacapavir in the setting of Y188L NNRTI resistance mutation during pregnancy, resulting in successful maternal viral suppression and prevention of vertical transmission of HIV. A 24-year-old woman with prior poor adherence, socioeconomic instability, and NNRTI resistance (Y188 L mutation) presented with uncontrolled viremia during her second pregnancy. After consultation with perinatal HIV experts, she initiated a long-acting injectable regimen combining lenacapavir (927 mg subcutaneous every 6 months) and cabotegravir/rilpivirine (600/900 mg intramuscular every 2 months). Rapid viral load reduction was achieved, declining from 147,351 to 67 copies/mL within weeks. Despite transient hepatotoxicity, the patient delivered an HIV-negative infant at term. Maternal HIV RNA remained <50 copies/mL postpartum and became undetectable by January 2025. The infant remained HIV-negative at 18-months follow-up. This case demonstrates the potential role of long-acting antiretroviral therapy (ART) in achieving sustained virologic control among pregnant patients with adherence challenges and drug resistance. While lenacapavir shows promise as a biannual agent addressing barriers to adherence, its pharmacokinetics and safety during pregnancy remain uncharacterized. These findings underscore the urgent need for systematic studies and pregnancy registries evaluating long-acting ART agents in maternal populations to optimize outcomes and eliminate vertical transmission in hard-to-treat cases.
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