Background
Baseline rilpivirine drug resistance mutations (DRMs) are a risk factor for virological failure in patients treated with long-acting cabotegravir and rilpivirine (CAB/RPV LA). We investigated rilpivirine cross-resistance in experienced patients in Mexico, where Efavirenz (EFV) was the preferred initial ARV drug for more than 10 years.
Methods
Genotypic sequence data from 2442 patients experiencing at least two treatment failures were included for analysis. Pol sequences were submitted to Stanford HIVdb v9.6 to identify rilpivirine DRMs. The following mutations were included as rilpivirine DRMs (Stanford HIVdb penalty score ≥10): A98G, V100IV, K101EPH, V106I, E138AGKQR, V179DEFL, Y181CFGISV, Y188FL, G190ACEQSTV, H221Y, F227C, and 230IL. Resistance profiles were categorized as susceptible (including potential low-level resistance), intermediate (including low-level resistance), or high-level resistance.
Results
Patients failing two or more ART combinations (n = 2442) were included, all belonging to subtype B virus. All patients have experienced one treatment failure to NNRTIs, mostly to EFV. Of those, 1644 (67.3%) presented with at least one NNRTI DRM, including 619 (25.3%) with at least one rilpivirine DRM and 361 (21.9%) with at least two rilpivirine DRMs. Rilpivirne DRMs or combinations with more than 5% frequency are presented in Figure. DRMs related to EFV failure were the most frequent found. More than three quarters of patients with NNTRI-DRMs, showed intermediate (25.3%; n = 416) and high-level rilpivirine resistance (44.2%; n = 727). Considering all the genotypes studied (n=2442), we found intermediate rilpivirine resistance in 415 cases (17.0%) and high-level resistance in 728 (29.8%).
Conclusions
This retrospective analysis indicates that rilpivirine DRMs are common in a setting wherein NNRTI-based treatment was widely implemented, and has implications for operational implementation of CAB/RPV LA. Screening for existing DRMs is logistically and technically challenging in Mexico and could be a barrier to use of CAB/RPV LA.