A6 HIV Subtype in a Pharmacist-Directed Cabotegravir/Rilpivirine Screening Protocol

To the Editor:

Cabotegravir with rilpivirine (CAB/RPV) parenteral monthly/bimonthly injections are recommended in persons living with HIV (PLWH) as an optimization strategy with suppressed viral loads (VLs) or with viremia, if adherence barriers exist with daily oral antiretroviral (ARV) regimens. ^1,2 Real-world CAB/RPV implementation programs demonstrate the necessity of a thorough screening protocol for optimal candidacy and persistence. ³ The report by Nguyen et al. demonstrates that CAP/RPV maintained VL suppression in 61 persons transitioned from oral therapy with VL failures in 3 PLWH with on-time injections. ³ All three developed non-nucleoside reverse transcriptase inhibitor (NNRTI) or integrase strand transfer inhibitor (INSTI) resistance at VL rebound. One PLWH had baseline NNRTI mutations which may be unknown if historic ARV use is incompletely documented. Predictors of CAB/RPV poor response with VL rebound exist in the Phase 3 trials and include body mass index (BMI) >30 kg/m², HIV subtype A1 or A6, baseline NNRTI or INSTI resistance and low CAB/RPV therapeutic drug concentrations. ⁴ Recently presented data demonstrate the A1 subtype may be less concerning with VL suppression maintained at week 48 in PLWH optimized to CAB/RPV in Kenya, Uganda, and South Africa. The A6 HIV subtype was originally demonstrated in persons from Russia as a variable of concern for CAB/RPV failure. ⁴

We describe a recent evaluation for CAB/RPV candidacy in a similar pharmacy-driven screening program at an academic medical center in a perinatally infected 17-year-old PLWH. Based on our clinic protocol, a pre-approval proviral genotype demonstrated an A6 HIV serotype. HIV VL suppression with oral ARVs was maintained for 13 years but upon historical record review, the patient was a Ukraine immigrant. Based on the BMI >30 kg/m² and the A6 subtype, continuation of oral ARV therapy is recommended. ⁴

The HIV proviral assay may assist in determining the HIV subtype and any archived NNRTI/INSTI mutations. Previously reported CAB/RPV screening protocols document using the proviral assay as an additional testing strategy for optimal evaluation of historic resistance. ⁵ Although the proviral assay sensitivity is low and some PLWH with baseline resistance may remain suppressed with archived NNRTI/INSTI mutations on CAB/RPV optimization, the HIV subtype is included in the test results. ⁶ The subtype provides an additional assessment assisting with CAB/RPV treatment transition. In these authors’ 3 years of clinic CAP/RPV screening, baseline NNRTI resistance is common and one of the primary reasons for CAB/RPV exclusion, similar to the Nguyen et al. report. ³ Although non-B HIV subtypes are documented in our clinic experience, this is the first reported A6 result (n = 212 evaluated for parenteral transition with 71 active PLWH since April 2021). As documented by Nguyen et al. and this case report, a thorough screening protocol is necessary with consideration for subtype evaluation before CAB/RPV optimization based on the PLWH country of origin. ^3,5