The cumulative prevalence of HIV-1 drug resistance in perinatal HIV

Objective: To describe acquired drug resistance mutations (DRMs) amongst children and adults with perinatal HIV stratified by age. Design: Retrospective observational cohort study. Methods: Data on demographics, antiretroviral therapy (ART), viral load (VL), CD4 count and lifetime cumulative acquired DRMs was collected and disaggregated by birth era; pre and post 2000; 0–24 and ≥ 25 years (n 113 vs 167). Results: 280 individuals (median age 26 years, interquartile range 21,30), 235 (84%) Black ethnicity, 160 (57%) female, with median ART exposure 17 years. 99.6% currently on ART, 205 (73%) integrase strand transfer inhibitor (INSTI) regimens, with 252 (90%) VL<200 copies/ml. 121/280 (43%) acquired resistance to ≥ one ART class (37% 0–24 versus 47% ≥ 25 years), 69/280 (25%) ≥ two (14% v 32%), and 13/280 (4.6%) ≥ three class; 11/13 (85%) aged ≥ 25 years. DRMs by ART class; 104/280 (37%), non-nucleoside reverse transcriptase inhibitor (NNRTI), 78 (28%) nucleoside reverse transcriptase inhibitor (NRTI), 15 (5%) protease inhibitor and 4 (1%) INSTI. Uni/multivariate analysis; DRM acquisition was significantly associated with >2 anchor class exposure (p = 0.000), prior AIDS diagnosis (p = 0.001, 0.085) and early mono/dual NRTI exposure (p = 0.000, 0.029). Conclusion: Despite improved ART efficacy, DRMs limit treatment options, including to long-acting injectable therapies with one third having NNRTI-DRMs. Outcomes for second-generation INSTIs are promising with low rates of resistance but require continued monitoring. Whilst multi-drug resistance rates are lower in those born post-2000, over a third already have DRMs, highlighting the ongoing need for patient-centred approaches addressing adherence and novel ART class development.