Persistent Virologic Failure and Dynamic Genotypic Resistance Shifts in a Perinatally HIV-Infected Adolescent.

Abstract

A 16-year-old female with perinatally acquired HIV had persistent virology failure despite documented adherence and multiple regimen changes. Sequential genotypic testing over 13 months showed an unusual shift: April 2024—HIV-1 subtype C with non-nucleoside reverse transcriptase inhibitors (NNRTI) mutation K103N (high-level EFV/NVP resistance) and no integrase strand transfer inhibitor (INSTI) resistance; May 2025—loss of K103N (NNRTI susceptibility restored) but emergence of major INSTI mutations G118R and E138K (± accessory P142T), conferring high-level resistance to all INSTIs (bictegravir, cabotegravir, dolutegravir, elvitegravir, raltegravir). NRTI and PI susceptibility persisted. This rare reversal–emergence sequence highlights viral evolution under selective pressure and the need for repeat resistance testing before regimen switches in resource-limited settings. The patient remains clinically stable. Viral load 197,000 copies/mL in May 2025, pending regimen optimization.