Drug resistance and optimizing dolutegravir regimens for adolescents and young adults failing antiretroviral therapy. (1st September 2019)

• Record Type: Journal Article
• Authors: Kouamou, Vinie; Manasa, Justen; Katzenstein, David; McGregor, Alan M.; Ndhlovu, Chiratidzo E.; Makadzange, Azure T.
• Is Part Of: AIDS. Volume 33:Number 11(2019)
• Publication Date: 2019-09-01
• Subjects: adherence -- adolescents and young adults -- genotyping -- HIV drug resistance -- HIV-1 -- Zimbabwe; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000002284
• Languages: English
• ISSNs: 0269-9370

Abstract

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.