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

To describe acquired drug resistance mutations (DRMs) among children and adults with perinatal HIV stratified by age.

A retrospective observational cohort study.

Data on demographics, antiretroviral therapy (ART), viral load, CD4 + cell count, and lifetime cumulative acquired DRMs was collected and disaggregated by birth era; pre and post 2000; 0-24 and at least 25 years ( n  = 113 vs. 167).

Two hundred eighty individuals (median age 26 years, interquartile range 21-30), 235 (84%) Black ethnicity, 160 (57%) female, with median ART exposure 17 years. About 99.6% currently on ART, 205 (73%) integrase strand transfer inhibitor (INSTI) regimens, with 252 (90%) viral load less than 200 copies/ml. One hundred twenty-one of 280 (43%) acquired resistance to at least one ART class (37% 0-24 vs. 47% ≥ 25 years), 69/280 (25%) at least two (14 vs. 32%), and 13/280 (4.6%) at least three class; 11/13 (85%) aged at least 25 years. DRMs by ART class; 104/280 (37%), nonnucleoside 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 more than two 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).

Despite improved ART efficacy, DRMs limit treatment options, including 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. While multidrug resistance rates are lower in those born post2000, over one-third already have DRMs, highlighting the ongoing need for patient-centered approaches addressing adherence and novel ART class development.