Background:
Since 2018, the World Health Organization has recommended dolutegravir- (DTG-) based antiretroviral therapy (ART) as the preferred regimen for most people with HIV. Most African countries have thus shifted from non-nucleoside transcriptase inhibitor- (NNRTI-) to DTG-based ART, often without requiring prior viral suppression and without access to resistance testing in case of viremia. National programs report higher rates of viral suppression since changing to DTG, including among people with unsuppressed viremia before the change. To date, few DTG resistance-associated mutations (RAMs) have been reported from African routine care cohorts.
Methods:
This study aims to assess emerging DTG RAMs among participants of the Viral Load Cohort North-East Lesotho (VICONEL). Eligibility criteria were i) written informed consent, ii) having changed from NNRTI- based to DTG-based ART, and iii) subsequently having ≥2 viral loads ≥50 copies/mL (c/mL), including at least one available sample ≥500 c/mL and taken ≥18 months after changing to DTG (data closure: April 20, 2023). For each participant, the last-available sample with a viral load ≥500 c/mL, as well as previous samples if DTG RAMs were detected, were analysed near full-length HIV sequencing for genotypic resistance testing (GRT). RAMs were interpreted using the Stanford HIVdb (9.5.0).
Results:
Among 14’881 VICONEL participants who had changed to DTG ≥18 months before data closure, 75 (0.5%) fulfilled the inclusion criteria (median age at change 27 years, 57% female). GRT were available for 54/75 (72%). Among these 54 participants (median age at change 24 years, 54% female), high-level and low-level resistance to DTG was detected in five and one, respectively. None of these six had a documented viral load <50 c/mL <6 months before changing to DTG (Figure). DTG RAMs detected were H51Y (participant 6 in Figure), E92Q (6), G118R (1,2,3,5), E138A (3), E138K (1,2,3,5), N155H (4), and R263K (1,4,5). GRT data from before the change to DTG were available for three of these six participants (participants 1, 3, 6 in Figure): in all cases, RAMs against the nucleoside reverse transcriptase inhibitor backbone but no RAMs in the integrase region were recorded before change.
Conclusions:
Among participants who changed from NNRTI- to DTG-based ART with sustained viremia ≥18 months after change, DTG resistance was more frequent than expected, highlighting the need for national programs to ensure close follow-up with access to GRT for this specific subgroup.
