Patterns of HIV-1 Drug Resistance After First-Line Antiretroviral Therapy (ART) Failure in 6 Sub-Saharan African Countries: Implications for Second-Line ART Strategies

TLDR: After stavudine failure in African populations, zidovudine rather than tenofovir may be preferred in second-line ART, and early failure detection limited the accumulation of resistance.

Abstract: was used to score major DRMs. The Stanford algorithm was used to predict drug susceptibility. Results. HIV-1 sequences were generated for 142 participants who virologically failed ART, of whom 70% carried $1 DRM and 49% had dual-class resistance, with an average of 2.4 DRMs per sequence (range, 1‐8). The most common DRMs were M184V (53.5%), K103N (28.9%), Y181C (15.5%), and G190A (14.1%). Thymidine analogue mutations were present in 8.5%. K65R was frequently selected by stavudine (15.0%) or tenofovir (27.7%). Among participants with $1 DRM, HIV-1 susceptibility was reduced in 93% for efavirenz/nevirapine, in 81% for lamivudine/emtricitabine, in 59% for etravirine/rilpivirine, in 27% for tenofovir, in 18% for stavudine, and in 10% for zidovudine. Conclusions. Early failure detection limited the accumulation of resistance. After stavudine failure in African populations, zidovudine rather than tenofovir may be preferred in second-line ART. Strategies to prevent HIV-1 resistance are a global priority.