Prevalence and patterns HIV-1 drug resistance among patients experiencing persistent low-level viremia on first-line antiretroviral therapy in Uganda

Abstract

The emergence of HIV-1 drug resistance during the course of antiretroviral therapy limits the success of treatment programs. Evidence has shown that HIV infected people experiencing periods of persistent low-level viremia (PLLV) have later on developed virological failure. In addition to this, there is limited resistance data available to confirm the existence of drug resistance mutations as the driver of virological failure (Kiweewa et al., 2019). This aim of this study was to describe the prevalence and patterns of HIV drug resistance (HIVDR) among people living with HIV (PLHIV) experiencing PLLV within the Ugandan population. Using a retrospective cross-sectional study design, the second plasma sample from patients with HIV-RNA levels between ≥50 and <1000cp/mL in at least two viral load determinations over a twelve-month period having an adherence score of ≥95% was picked. A total of 444 eligible plasma specimen were selected from patients taking the recommended first line antiretroviral therapy (ART) drug combinations. Of these samples, 202/444 were from patients taking a Dolutegravir (DTG) containing regimen. Sample genotyping was performed in order identify mutations existing within the protease, reverse transcriptase and integrase regions of the polymerase genome. Study results revealed an overall HIVDR prevalence of 62.12% (CI 51.45 - 48.54). The HIVDR prevalence was further classified by ART drug class: the prevalence rate was highest 56.06% (CI 44.6-66.85) among the non-nucleoside reverse transcriptase inhibitors (NNRTIs). This was followed by the nucleoside reverse transcriptase inhibitors (NRTIs) which had an HIVDR prevalence of 42.2 % (CI 32.58-52.90). The integrase strand transfer inhibitors (INSTIs) had an HIVDR prevalence of 3.70% (0.45-24.54) whereas the lowest prevalence of 1.52% (CI 0.02-12.90) was found among the protease inhibitors (PIs). When individual drug resistance associated mutations (DRAMs) were further assessed: the NRTI-M184V/I and K65R mutations were the most prevalent at 40.3% and 14.9% respectively. The NNRTI resistance mutations K103E/N/S and G190A were the most prevalent at 30% and 19.4% respectively. The INSTI-N155H, R263K and PI-M46I drug resistance mutations had the lowest HIVDR prevalence of 1.5%. Mutations were more frequent among patients with HIV-1 subtype A with a duration on ART of 11-120 months. The presence of a high HIVDR towards Efavirenz and Nevirapine justifies the transition to use Dolutegravir in first line ART. The results further confirm the existence of low HIVDR towards Dolutegravir demonstrating emerging resistance to DTG in an era of less than five years of use of this drug.