HIV drug resistant mutations associated with virological failure among HIV-1 zero positive infants in Uganda after intensified adherence counseling

Abstract

Paediatric HIV treatment is setback by poor adherence and emerging drug resistance. This longitudinal cohort study assessed the impact of intensified adherence counselling (IAC) on viral suppression and the development of HIV drug resistance mutations in HIV-positive infants receiving antiretroviral therapy (ART). 100 HIV-positive infants (aged 4–12 months) with unsuppressed viral loads (>1000 copies/mL) were enrolled at the Joint Clinical Research Centre (JCRC), Uganda. Mother-infant pairs received IAC for a period of three months. After three months, re-evaluation was conducted, during which HIV viral load was measured using the Abbott assay and adherence was assessed using the pill-count method. Infants with persistent viremia were subjected to drug resistance testing using next-generation sequencing using a MiSeq from which the resulting FASTA files were downloaded from Hydra and submitted to the Stanford University HIV Drug Resistance Database (Version 9.8). The output, provided as a Comma-Separated Values (CSV) file, included classified mutations, mixtures, corresponding scores, susceptibility status, and other relevant parameters. A tabular summary of these findings was then generated to facilitate interpretation and further analysis. Intensified Adherence Counselling (IAC) in mother–infant pairs prompted better results in viral suppression despite changes in adherence, with viral loads continually decreasing after IAC compared to before IAC. HIV drug resistance mutations showed changes in both NRTI and NNRTI profiles. The common NRTI mutation M184V/I reduced slightly post-IAC (43.5% to 40.2%), while increase in TAM-associated mutations (K219, K70, D67) suggested ongoing selective pressure from thymidine-based regimens. NNRTI resistance showed an overall decline, with major mutations such as K103N and Y181C decreasing significantly after IAC, with the disappearance of variants like E138Q and G190S, confirming improved viral suppression and reduced propagation of resistant quasispecies. Mixture mutation analysis showed reductions in NRTI (M184, K219) and NNRTI (V179, V108, Y181, V106) variants, further indicating suppression of resistant viral populations. Emergence and persistence of mutations such as E138A, K238, P225H reflects ongoing viral suppression under treatment pressure. Overall, IAC contributed to improved viral control and reductions in several resistance-associated variants, though there is a continued need for vigilant resistance monitoring and optimized ART regimens.