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Drug resistance and optimizing dolutegravir regimens for adolescents and young adults failing antiretroviral therapy

Kouamou, Viniea; Manasa, Justenb; Katzenstein, Davidc; McGregor, Alan M.a; Ndhlovu, Chiratidzo E.a; Makadzange, Azure T.a

doi: 10.1097/QAD.0000000000002284

Objectives: The integrase strand inhibitor dolutegravir (DTG) combined with tenofovir and lamivudine (TLD) is a single tablet regimen recommended for 1st, 2nd and 3rd-line public health antiretroviral therapy (ART). We determined drug resistance mutations (DRMs) and evaluated the predictive efficacy of a TLD containing regimen for viremic adolescents and young adults in Harare, Zimbabwe.

Methods: We sequenced plasma viral RNA from HIV-1-infected adolescents and young adults on 1st and 2nd-line ART with confirmed virologic failure (viral load >1000 copies/ml) and calculated total genotypic susceptibility scores to current 2nd, 3rd line and DTG regimens.

Results: A total of 160 participants were genotyped; 112 (70%) on 1st line and 48 (30%) on 2nd line, median (interquartile range) age 18 (15–19) and duration of ART (interquartile range) was 6 (4–8) years. Major DRMs were present in 94 and 67% of 1st and 2nd-line failures, respectively (P < 0.001). Dual class resistance to nucleotide reverse transcriptase inhibitors and nonnucleotide reverse transcriptase inhibitors was detected in 96 (60%) of 1st-line failures; protease inhibitor DRMs were detected in a minority (10%) of 2nd-line failures. A total genotypic susceptibility score of 2 or less may risk protease inhibitor or DTG monotherapy in 11 and 42% of 1st-line failures switching to 2nd-line protease inhibitor and TLD respectively.

Conclusion: Among adolescents and young adults, current protease inhibitor-based 2nd-line therapies are poorly tolerated, more expensive and adherence is poor. In 1st-line failure, implementation of TLD for many adolescents and young adults on long-term ART may require additional active drug(s). Drug resistance surveillance and susceptibility scores may inform strategies for the implementation of TLD.

aDepartment of Medicine

bDepartment of Medical Microbiology, College of Health Sciences, University of Zimbabwe

cDepartment of Molecular Biology, Biomedical, Research and Training Institute, Harare, Zimbabwe.

Correspondence to Vinie Kouamou, Department of Medicine, College of Health Sciences, University of Zimbabwe, PO Box A178, Avondale, Harare, Zimbabwe. E-mail:

Received 3 February, 2019

Revised 27 May, 2019

Accepted 29 May, 2019

Copyright © 2019 Wolters Kluwer Health, Inc.