Evaluation of HIV-1 drug resistance among patients failing first-line antiretroviral therapy in Ethiopia.

OBJECTIVE: The aim of this study was to evaluate HIV-1 drug resistance among patients failing first-line antiretroviral therapy in Ethiopia.

METHOD: A total of 699 HIV-infected adults (≥15 years) who failed first-line ART were recruited between 2017 and 2019 from 63 ART-providing sites in Ethiopia. Treatment failure was defined as patients with two consecutive viral loads ≥1000 copies/ml within 6 months of follow-up. The pol gene region of HIV-1 was amplified and sequenced using in-house assay of China CDC. The Stanford HIVDB v9.0 algorithm was used for identification of resistance mutations. Resistance mutations were characterized according to the 2019 International AIDS Society-USA mutation list. P-value of <0.05 were considered statistically significant during multivariate analysis which was done using SPSS v26.0.

RESULTS: Overall HIVDR among patients failing first-line therapy in Ethiopia was 77.8%. NNRTI and NRTI resistance was 75.7% and 71.2%, respectively. NVP and EFV accounted for 74.2% and 60.8% HIVDR, respectively. About half (48.1%) of NRTI associated mutations were responsible for Abacavir while 34% were for multi-NRTI resistance. Mutations responsible for the commonly used EFV and NVP accounted 62.9% while resistance to Etravirine, Doravirine and Rilivirine, which were not part of the country's ART program, were 37.1% and could be explained by cross-resistance within the drug class. PI associated resistance was detected only in 1.6% of the study participants. The most common mutations identified were M184V (30.1%), K103N (18.7%), Y181C (13.6%) and K65R (12.1%). In a multivariate logistic regression analysis, predictors of HIVDR were prior ART exposure (AOR=2.3; 95%CI=1.8, 3.6), absence of HIV status disclosure (AOR=2.05; 95%CI=1.26, 3.35), CD4 count of ≤200 cells/mm3 (AOR= 1.94; 1.213, 3.125) and bedridden status (AOR=4.16; 95%CI=3.21, 5.16).

CONCLUSIONS: The high-levels of HIVDR among patients with failure of first-line ART in Ethiopia calls for individualized HIVDR testing. Mutations associated with multi-NRTI and NNRTI cross-resistance may alert the program for considering drugs of higher genetic barrier targeting protease and other regions. Patients with low CD4 count and bedridden should be given attention for the potential HIVDR during the clinical management.

KEY WORDS: ART; Cross-resistance; Drug resistance mutations; HIV-1.