Multiclass HIV drug resistance: Case series of treatment-experienced PLHIV with resistance to all antiretroviral classes in Northern Uganda

Abstract

Introduction Multiclass HIV drug resistance (HIVDR) is an emerging public health challenge in Uganda, especially among treatment-experienced individuals with long antiretroviral therapy (ART) histories. Resistance across nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) limits treatment options and threatens program sustainability. This study describes three cases of multiclass HIVDR in West-Nile region of Uganda. Methods A descriptive case series was conducted among people living with HIV (PLHIV) with documented virological failure and confirmed resistance to all four ART classes between January 2023 and December 2024. HIVDR testing used next-generation sequencing, and resistance mutations were interpreted with Stanford HIVDR database. Clinical data were abstracted and analyzed descriptively. Results Three cases were identified: two females (20 and 42 years) and one male (14 years), after approximately 10 years on ART. Shared factors included delayed viral load (VL) monitoring, prolonged exposure to failing regimens, delayed resistance testing and adherence challenges related to stigma and psychosocial barriers. All had been exposed to dolutegravir (DTG)-based regimens and developed intermediate-to-high level resistance to DTG alongside mutations in the other classes. Two cases achieved viral suppression < 1000 copies/ml on salvage therapy. Conclusion These cases demonstrate that high-barrier drugs like DTG and Darunavir remain vulnerable when virological failure persists and adherence is suboptimal. Strengthening VL monitoring, access to genotypic testing and adherence support is essential to prevent Multiclass HIVDR.