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

Publication Date: 
Sunday, July 29, 2018
Fily F, Ayikobua E, Ssemwanga D, Nicholas S, Kaleebu P, Delaugerre C, Pasquier E, Amoros Quiles I, Balkan S, Schramm B

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:
78 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.

Publisher: 
Trop Med Int Health