Prevalence of HIV-1 drug resistance mutations in proviral DNA in the Swiss HIV Cohort Study, a retrospective study from 1995 to 2018. Journal of Antimicrobial Chemotherapy
Jaha and Schenkel et al. developed a protocol to perform proviral DNA genotypic resistance testing and evaluated the prevalence of drug resistance mutations (DRM) among people with HIV in the Swiss HIV Cohort Study.
As standard genotypic resistance testing can only be performed among individuals with replicating HIV infection, resistance testing in proviral DNA has been proposed for individuals with low or undetectable HIV viral loads. In this study, cohort participants with available PBMC samples from Lausanne and Geneva were included. Near full-length HIV-1 DNA amplification was performed and sequenced using next-generation sequencing (NGS). DRMs were systematically assessed using the Los Alamos and the Stanford HIV Drug Resistance Database. As certain mutations induced by the APOBEC enzymes could result in defective non-replicable viruses, a sensitivity analysis without those mutations was performed.
The study included PBMC samples from 962 individuals (mean age 40 years, 33% women, median CD4+ 495 cells/μL). Amplification and NGS was successful in 71%, with samples from individuals with a low CD4 cell count, and samples with a high DNA concentration being more likely to be successfully amplified. At least one DRM was detected in 55% of patients, with DRMs against NRTI being most frequently detected, followed by NNRTI, protease and integrase inhibitors. After excluding mutations potentially induced by APOBEC, 43.8% had at least one DRM.
Taken together, the authors presented a reliable method to perform genotypic resistance testing from HIV proviral DNA in a diverse population of people with HIV. More studies are needed to evaluate the clinical implication of these DRMs and to guide treatment decisions among people with low or undetectable HIV viral loads.