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. 2019 Sep 1;33(11):1729-1737.
doi: 10.1097/QAD.0000000000002284.

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

Vinie Kouamou  1 , Justen Manasa  2 , David Katzenstein  3 , Alan M McGregor  1 , Chiratidzo E Ndhlovu  1 , Azure T Makadzange  1
Affiliations

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

Vinie Kouamou et al. AIDS. .

Abstract

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.

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Conflict of interest statement

Potential conflicts of interest. At the time of conception and the initial conduct of the study ATM had no reported conflicts of interest and was funded through an NIH K-grant. However, ATM is now an employee of Gilead Sciences. All other authors have no reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

References

    1. Ministry of health. MOHCCZimbabweOSDM2017.pdf. 2017.
    1. ZIMPHIA. ZIMPHIA Preliminary Findings_Nov 2016 DOC-20161202-WA0004.pdf. 2016.
    1. World Health Organization. Treat All: policy adoption and implementation status in countries. 2017.
    1. Ferrand RA, Briggs D, Ferguson J, Penazzato M, Armstrong A, MacPherson P, et al. Viral suppression in adolescents on antiretroviral treatment: review of the literature and critical appraisal of methodological challenges. Trop Med Int Health [Internet]. 2016. March 1 [cited 2018 Nov 28];21(3):325–33. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/tmi.12656 - DOI - PMC - PubMed
    1. Makadzange AT, Higgins-Biddle M, Chimukangara B, Birri R, Gordon M, Mahlanza T, et al. Clinical, Virologic, Immunologic Outcomes and Emerging HIV Drug Resistance Patterns in Children and Adolescents in Public ART Care in Zimbabwe Sluis-Cremer N, editor. PLOS ONE [Internet]. 2015. December 14 [cited 2018 Feb 12];10(12):e0144057 Available from: http://dx.plos.org/10.1371/journal.pone.0144057 - DOI - PMC - PubMed

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