HIV-1 drug resistance among pregnant and breastfeeding mothers and its association with paediatric HIV infections in the Dolutegravir era in Uganda

OBJECTIVES: To determine the prevalence and patterns of HIV drug resistance mutations among pregnant and breastfeeding women in Uganda following the rollout of dolutegravir, characterize circulating HIV-1 subtypes and their association with resistance, and identify factors associated with vertical HIV transmission. MATERIALS AND METHODS: This study involved 46 pregnant and 154 breastfeeding mothers in Uganda with viral loads (VLs) >1000 copies/mL. Residual plasma underwent genotypic resistance testing on the Illumina MiSeq platform, and HIVDRMs and subtypes were interpreted using the Stanford HIVdb algorithm. Participant characteristics were summarized descriptively, and associations between subtypes, HIVDRMs, and vertical transmission were assessed using chi-square tests, t-tests, and logistic regression. RESULTS: Among 200 participants, 53.0% (95% CI: 46.0-59.9) had resistance to at least one antiretroviral therapy (ART) class. HIVDRM prevalence was 41.5% (CI: 34.8-48.5) for NNRTIs, 20.5% (CI: 15.4-26.7) for NRTIs, 4.0% (CI: 2.0-7.8) for PIs and 3.5% (CI: 1.7-7.2) for INSTIs. Notably, 13.5% had accessory mutations, including T97A, which can contribute to DTG resistance. HIV-1 subtypes A (57.0%) and D (30.5%) were most common, with few subtype C (6.5%) and recombinant forms (6.0%). Subtype D and routine/repeat VL monitoring following intensive adherence counselling were associated with HIVDRMs (P = 0.01 and P = 0.04 respectively). Seven infants tested HIV-1 positive, with poor maternal adherence and repeat VL significantly associated with seropositivity (P = 0.004 and P = 0.027, respectively). CONCLUSION: This high HIVDRM burden highlights the urgent need for routine resistance testing, subtype-specific treatment strategies and improved ART adherence support to reduce mother-to-child-transmission, particularly in women with subtype D infections.