HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy: a collaborative cohort analysis. Lancet HIV
Loosli et al. assessed risk factors for dolutegravir (DTG) resistance and patterns of drug resistance mutations (DRM) among people with HIV (PWH) and replicating HIV infection on DTG-containing antiretroviral therapy (ART). For this international collaboration, the authors combined data from the ART Cohort Collaboration (ART-CC) and the International epidemiology Databases to Evaluate AIDS (IeDEA), thereby including PWH from Europe, North America and South Africa.
Participants who underwent genotypic resistance testing while receiving DTG-based ART were included in the study. The authors calculated adjusted odds ratios (aOR) with multivariable logistic regression to identify risk factors for DTG resistance according to the Stanford HIV Database algorithm.
The study included 599 individuals with available drug resistance testing. The majority of individuals were male (69%), the median age was 44 years (interquartile range [IQR] 36-52), and the median CD4 cell count at resistance testing was 412 cells/μL (IQR 213-674). Most individuals (68%) did not have prior exposure to first-generation integrase inhibitors (e.g. raltegravir, elvitegravir). Drug resistance mutations against integrase inhibitors were present in 86 (14%) of all individuals, and 36 individuals (6%) had DRMs affecting DTG: 13 individuals acquired low-level DTG resistance, 17 had intermediate DTG resistance, and 6 showed high-level DTG resistance. Dolutegravir resistance was more likely to occur among individuals who received DTG monotherapy (aOR 34.1, 95% CI 9.9 – 117.0), among persons on dual therapy (DTG/lamivudine: aOR 9.2, 2.2 – 38.6), and among PWH and NRTI resistance mutations (low-level: aOR 5.2, 1.3 – 20.7; intermediate/high: aOR 13.4, 4.6 – 39.7).
In summary, individuals on DTG monotherapy or DTG/lamivudine dual therapy, and individuals with NRTI resistance are at increased risk to develop DTG resistance in the event of a virological failure. Although still rare, the present study highlights that DTG resistance does occur. Improved access to drug resistance testing for all PWH will be critical to monitor DTG resistance rates after its global roll-out.