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HIV ‐1 drug resistance testing at second‐line regimen failure in Arua, Uganda: avoiding unnecessary switch to an empiric third‐line
Author(s) -
Fily F.,
Ayikobua E.,
Ssemwanga D.,
Nicholas S.,
Kaleebu P.,
Delaugerre C.,
Pasquier E.,
Amoros Quiles I.,
Balkan S.,
Schramm B.
Publication year - 2018
Publication title -
tropical medicine and international health
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.056
H-Index - 114
eISSN - 1365-3156
pISSN - 1360-2276
DOI - 10.1111/tmi.13131
Subject(s) - medicine , darunavir , drug resistance , regimen , viral load , hiv drug resistance , protease inhibitor (pharmacology) , integrase inhibitor , resistance mutation , telaprevir , virology , antiretroviral therapy , human immunodeficiency virus (hiv) , reverse transcriptase , biology , virus , microbiology and biotechnology , rna , biochemistry , hepatitis c virus , ribavirin , gene
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/mm 3 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 CD 4 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 CD 4 count might be an indicator of third‐line drug requirement for patients failing second‐line therapy.