HIV‐1 drug resistance testing at second‐line regimen failure in Arua, Uganda: avoiding unnecessary switch to an empiric third‐line

Objectives The number of patients on second‐line antiretroviral therapy is growing, but data on HIV drug resistance patterns at failure in resource‐constrained settings are scarce. We aimed to describe drug resistance and investigate the factors associated with extensive resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), in patients failing second‐line therapy in the HIV outpatient clinic at Arua Regional Referral Hospital, Uganda. Methods We included patients who failed on second‐line therapy (two consecutive viral loads ≥1000 copies/mm3 by SAMBA‐1 point‐of‐care test) and who had a drug resistance test performed between September 2014 and March 2017. Logistic regression was used to investigate factors associated with NRTI genotypic sensitivity score (GSS) ≤1. Results Seventy‐eight patients were included: 42% female, median age 31 years and median time of 29 months on second‐line therapy. Among 70 cases with drug resistance test results, predominant subtypes were A (47%) and D (40%); 18.5% had ≥1 major protease inhibitor mutation; 82.8% had ≥1 NRTI mutation and 38.5% had extensive NRTI resistance (NRTI GSS ≤1). A nadir CD4 count ≤100/ml was associated with NRTI GSS ≤1 (OR 4.2, 95% CI [1.3–15.1]). Thirty (42.8%) patients were switched to third‐line therapy, composed of integrase inhibitor and protease inhibitor (60% darunavir/r) +/− NRTI. A follow‐up viral load was available for 19 third‐line patients at 12 months: 84.2% were undetectable. Conclusions Our study highlights the need for access to drug resistance tests to avoid unnecessary switches to third‐line therapy, but also for access to third‐line drugs, in particular integrase inhibitors. Low nadir CD4 count might be an indicator of third‐line drug requirement for patients failing second‐line therapy. Objectifs Le nombre de patients sous traitement antirétroviral de seconde ligne est en augmentation, mais les données sur les profils de résistance du VIH aux médicaments en cas d’échec sont rares dans les pays à ressources limitées. Nous avons voulu décrire la résistance aux médicaments et investiguer les facteurs associés à une résistance étendue aux inhibiteurs nucléosidiques/nucléotidiques de la transcriptase inverse (INTI) chez les patients en échec de traitement de seconde ligne dans la clinique ambulatoire des patients VIH à l'Hôpital Régional de Référence d'Arua, en Ouganda. Méthodes Nous avons inclus des patients avec un échec de traitement de seconde ligne (deux charges