Background:
Long-acting antiretroviral therapy (LA-ART) is novel and has been used for both virologically-suppressed (VS) and viremic patients with adherence challenges. The currently-approved LA-ART combination – cabotegravir (CAB) and rilpivirine (RPV) – is limited by the relatively high prevalence (up to 10%) of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistant virus globally and is not endorsed for low-and-middle-income-countries (LMICs). The combination of LA lenacapavir (LEN) and CAB has not been studied in a clinical trial but poses promise for LMICs.
Methods:
Providers (MDs/pharmacists) at the UCSF Ward 86 Clinic, the UCSD Owen Clinic, MetroHealth in Cleveland, and the UPenn HIV Clinic used LEN subcutaneously every 6 months after oral loading in combination with CAB administered intramuscularly every 4 or 8 weeks in patients with adherence challenges to oral ART. A case series was assembled with the following data points: gender, age, housing insecurity and/or substance use, viral load (VL) prior to starting LEN/CAB, duration between CAB doses (every 4 or 8 weeks), whether RPV was maintained, viral mutations, whether VS (VL <75 copies/ml) was achieved on LEN/CAB, and if so, time to VS.
Results:
The Table shows patients in the case series (n=34; 76% male 24% cis/trans female; 41% Black; 38% Latino/a; median age 47 (range 28-75) years; 71% with CAB every 8 weeks). All patients had difficulty adhering to oral ART, with 56% reporting housing insecurity, substance use, or both. The reason(s) for either adding LA LEN to CAB/RPV (68%) or using LEN/CAB without RPV (32%) were documented/suspected NNRTI mutations (n= 21, 59%), INSTI mutations (n=5, 15%), high VL when switching or starting LA ART (n=6, 18%) or continued viremia on CAB/RPV alone (n=4, 12%). One patient was started on LEN + CAB/RPV due to a high body mass index and another had LA RPV intolerance. Injection sites reactions on LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 suppressed (VL <75) after starting LEN (94%) at a median of 8 weeks (4-16), with only 16 (47%) being suppressed at baseline.
Conclusions:
In this case series of 34 patients started on LEN every 6 months in combination with CAB every 4 or 8 weeks (with or without RPV), high rates of VS (94%) were seen. Reasons for using this combination included adherence challenges, underlying ART resistance (mostly to NNRTIs) or low-level viremia on CAB/RPV. This data supports a clinical trial of LEN/CAB to study this combination for global use.
