Virological Failure, HIV-1 Drug Resistance and Early Mortality in Adults Admitted to Hospital in Malawi: A Nested Observational Cohort Study

Abstract

Background: Antiretroviral therapy (ART) scale-up in sub-Saharan Africa (SSA) combined with weak routine virological monitoring has driven increasing HIV drug resistance. We investigated ART failure, drug resistance and early mortality among hospital inpatients in Malawi. Methods: An observational cohort study nested in a trial of urine-based TB screening in unselected HIV-positive adults followed up for 56-days. Patients taking ART for ≥6 months at hospital admission had frozen plasma samples tested for HIV-1 viral load. Those with HIV-1 RNA ≥1000 copies per mL had drug resistance testing by ultra-deep sequencing, with drug resistance defined as intermediate or high-level resistance using the Stanford HIVDR Algorithm Findings: Of 1316 patients recruited in the Malawi trial site between October 2015 and September 2017, 786 had taken ART for ≥6 months of whom 252/786 (32.1%) patients had viral load ≥1000 copies per mL (virological failure). Mean age was 38 years, 61.5% were female and median CD4 count was 60 cells/µL. Of 237 (94.0%) patients with HIV drug resistance results available, 195 (82.3%) had resistance to lamivudine, 128 (54.0%) to tenofovir and 219 (92.4%) to efavirenz. Resistance to at least 2 drugs was common (196/237, 82.7%) and this was associated with increased 2-month mortality (adjusted hazard ratio 1.7, 95% CI 1.2-2.4, p=0.004). Interpretation: Interventions are urgently needed and should target ART clinic, hospital and posthospital care, including differentiated care focusing on patients with advanced HIV, rapid viral load testing and routine access to drug resistance testing. Prompt diagnosis and switching to alternative ART could reduce early mortality among HIV-positive inpatients.