HIV-1 drug resistance among adults on integrase inhibitors with virologic failure at Medical Research Council, Uganda: Prevalence, associated factors and diagnostic accuracy of next generation sequencing

Abstract

Emerging evidence suggests a high rate of drug resistance (DR) associated with integrase strand transfer inhibitors (INSTIs) in developed countries, though there is limited information on DR during INSTI treatment in Uganda. With the increased use of INSTIs as first-line treatment, monitoring for DR using next-generation sequencing (NGS) has become essential. NGS can detect lower-frequency variants that may be missed by traditional Sanger sequencing (SS). This study assessed the diagnostic accuracy of NGS, prevalence and factors associated to DR among 175 adults living with HIV in Uganda who experienced virologic failure (VF) on INSTIs. Utilized the Illumina MiSeq platform in comparison to sanger, data were analyzed using stata v.18 and used logistic regression model at 5% level of significance. The study demonstrated that NGS achieved an overall accuracy of 100% in detecting major mutations. NGS identified INSTI DRMs in 4% (95% CI: 1.6– 8.0%) of adults at a ≥20% threshold and was able to detect both high and low-abundance variants. However, no variable was significantly associated to presence of DRMs. The study emphasizes the need for DR testing before antiretroviral therapy (ART) initiation due to the increasing use of INSTIs. It advocates for healthcare providers to adopt more sensitive diagnostic methods like NGS, and tailor antiretroviral therapies based on detailed resistance profiles to effectively manage and prevent drug-resistant HIV strains.