Background
In 2021, the first long-acting (LA) ART regimen cabotegravir/rilpivirine (CAB/RPV) was approved for people with HIV (PWH) with virologic suppression (VS). Demonstration projects show high rates of achieving VS among PWH with viremia at initiation, leading to US guidelines permitting this approach in 2024. Pre-existing resistance to either CAB or RPV reduces the effectiveness of the regimen. Lenacapavir (LEN) was approved for multidrug-resistant (MDR) HIV in late 2022. Here, we present outcomes from the largest real-world cohort to date of PWH receiving LEN at a single center.
Methods
Using electronic medical record data verified through clinician review, we assembled a case series from the Ward 86 Clinic in San Francisco to evaluate outcomes among PWH who initiated LA LEN for treatment. We recorded NNRTI or INSTI resistance, the reason for LEN initiation when not resistance-driven, and the backbone ART components with LEN. For PWH with baseline viremia (viral load >200 cp/ml), the time to VS (<50 cp/ml) was calculated using Kaplan–Meier.
Results
Overall, 50 participants starting LA LEN from March 2023-May 2025 were included in the analyses: 92% were on LA ART (31 on LEN/CAB and 15 on LEN + CAB/RPV) and 8% (4/50) were on LEN with an oral backbone. For the 62% on LEN/CAB only, the CAB was administered every 8 weeks. Mean age was 48 (SD 12.4); 70% men; 22% women, 8% gender diverse; 34% Black, 34% Hispanic, 24% White, 7% multiracial/other; 40% housing instability; 40% with substance use. The most common ART regimen prior to LEN was INSTI-based (54%). Documented baseline NNRTI resistance was high (70%), and baseline INSTI resistance low (10%). Beyond resistance, reasons for initiating LEN included slow viral decay (8%), persistent low-level viremia (6%) or injection site reactions on CAB/RPV (2%). Roughly half (44%) of the PWH in this series had VS when initiating LEN. Among those with a viral load >50 prior to initiating LEN (56%), all achieved VS with a median time to VS of 29 days (SE 6 days; Figure).
Conclusions
In a cohort of 50 PWH in San Francisco with high rates of NNRTI resistance, VS rates increased from 44% to 100% with the addition of LEN, with all patients with a baseline VL >200 cp/ml achieving VS by week 15. The majority of PWH on LA LEN in our center were on an exclusively LA regimen (62% LEN/CAB; 30% LEN + CAB/RPV). These finding contribute to the growing body of evidence supporting LA LEN as a treatment option for PWH with underlying resistance to other LA agents.
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