Evaluation of two bioinformatic algorithms for the interpretation of HIV-1 drug resistance and subtyping in Cameroon: Translational application for ART optimization in low-and middle-income countries

Background: Efficient monitoring of HIV drug resistance (HIVDR) relies on standardized bioinformatics tools for accurate identification of drug resistance mutations (DRMs). Thus, we sought to compare the concordance of HIV-1 genotypic profiling from sequences analyzed with two commonly-used editing algorithms in low- and middle-income countries (LMICs). Methods: A laboratory-based comparative study was conducted among treatment-experienced people living with HIV attending the Chantal BIYA International Reference Centre in Yaoundé-Cameroon from October-2022 through July-2023. For each individual, raw data of HIV-1 sequences were analyzed simultaneously using RECall (semi-automated) vs. Exatype (automated) algorithms. Outputs were compared for DRMs, polymorphisms and subtyping between the two algorithms, with significance at p<0.05. Results: Overall, 221 participants were included (mean-age 32±15 years, 52.5% female). Validation of sequence quality was 70.1% (155/221) by RECall vs. 60.2% (133/221) by Exatype, Ka=0.78 (p<0.0001), indicating a good agreement between both algorithms. Importantly, a perfect concordance (100%) was found in HIV-1 clade inference (CRF02_AG [82/82], A1 [29/29], G [5/5], F2 [5/5] and others [12/12]). Similarly, high concordances were found for the identification of DRMs to protease-inhibitors (99.0%), nucleoside reverse-transcriptase inhibitors (98.0%), non-nucleoside reverse-transcriptase inhibitors (98.6%) and integrase-inhibitors (100.0%). The average turn-around-time was two-folds longer with RECall (5.5±1.7 min) vs. Exatype (2.5±1.1 min); giving a lower efficiency (i.e. validation rate/time) with RECall (12.7) vs. Exatype (24.1). Conclusions: Semi-automated (RECall) and automated (Exatype) tools showed excellent agreement in detecting HIV-1 clades and DRMs, supporting their interoperability in clinical practice. Following efficiency, Exatype can be considered preferential, while RECall remains a quite suitable alternative for LMICs.