High prevalence of NRTI and NNRTI drug resistance among ART-experienced, hospitalized inpatients.

BACKGROUND Patients hospitalized with advanced HIV have a high mortality risk. We assessed viremia and drug resistance amongst differentiated care services and explored whether expediting the switching of failing treatments may be justified. SETTING Hospitals in the Democratic Republic of Congo (HIV hospital), and Kenya (general hospital including HIV care). METHODS Viral Load (VL) testing and drug resistance (DR) genotyping were conducted for HIV-inpatients ≥15 years, on first-line ART for ≥6 months, and CD4≤350 cells/µL. Dual-class DR was defined as low, intermediate, or high-level DR to at least one NRTI and one NNRTI. ART-regimens were considered ineffective if dual-class DR was detected at viral failure (VL ≥1000 copies/ml). RESULTS Among 305 inpatients, 36.7% (Kenya) and 71.2% (DRC) had VL ≥1,000copies/mL, of which 72.9% and 73.7% had dual-class DR. Among viral failures on TDF-based regimens, 56.1% had TDF-DR and 29.8% AZT-DR, on AZT-regimens 71.4% had AZT-DR and 61.9% TDF-DR, respectively. Treatment-interruptions (≥48 hours during past 6 months) were reported by 41.7% (Kenya) and 56.7% (DRC). 56.2% (Kenya) and 47.4% (DRC) on TDF-regimens had TFV-DP concentrations <1250fmol/punch (suboptimal adherence). Among viral failures with CD4<100 cells/µL, 76.0% (Kenya) and 84.6% (DRC) were on ineffective regimens. CONCLUSIONS Many hospitalized, ART-experienced patients with advanced HIV were on an ineffective first-line regimen. Addressing ART-failure promptly should be integrated into advanced disease care packages for this group. Switching to effective second-line medications should be considered after a single high VL on NNRTI-based first-line if CD4≤350 cells/µL or, when VL is unavailable, among patients with CD4≤100 cells/µL.