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Moraka NO, Garcia-Broncano P, Hu Z, et al. Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana. AIDS. 2021;35(15):2413-2421doi: 10.1097/QAD.0000000000003041.
Moraka, N. O., Garcia-Broncano, P., Hu, Z., Ajibola, G., Bareng, O. T., Pretorius-Holme, M., Maswabi, K., Maphorisa, C., Mohammed, T., Gaseitsiwe, S., VanZyl, G. U., Kuritzkes, D. R., Lichterfeld, M., Moyo, S., & Shapiro, R. L. (2021). Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana. AIDS (London, England), 35(15), 2413-2421. https://doi.org/10.1097/QAD.0000000000003041
Moraka, Natasha Onalenna, et al. "Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana." AIDS (London, England) vol. 35,15 (2021): 2413-2421. doi: https://doi.org/10.1097/QAD.0000000000003041
Moraka NO, Garcia-Broncano P, Hu Z, Ajibola G, Bareng OT, Pretorius-Holme M, Maswabi K, Maphorisa C, Mohammed T, Gaseitsiwe S, VanZyl GU, Kuritzkes DR, Lichterfeld M, Moyo S, Shapiro RL. Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana. AIDS. 2021 Dec 01;35(15):2413-2421. doi: 10.1097/QAD.0000000000003041. PMID: 34324451; PMCID: PMC8631156.
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AIDS. 2021 Dec 01;35(15):2413-2421. doi: 10.1097/QAD.0000000000003041.

Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana.

AIDS (London, England)

Natasha Onalenna Moraka, Pilar Garcia-Broncano, Zixin Hu, Gbolahan Ajibola, Ontlametse T Bareng, Molly Pretorius-Holme, Kenneth Maswabi, Comfort Maphorisa, Terence Mohammed, Simani Gaseitsiwe, Gert U VanZyl, Daniel R Kuritzkes, Mathias Lichterfeld, Sikhulile Moyo, Roger L Shapiro

Affiliations

  1. Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
  2. Division of Medical Virology, Stellenbosch University Tygerberg, Cape Town, South Africa.
  3. Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts.
  4. Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School.
  5. Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health.
  6. Harvard Medical School, Boston, Massachusetts, USA.

PMID: 34324451 PMCID: PMC8631156 DOI: 10.1097/QAD.0000000000003041

Abstract

OBJECTIVE: To describe the occurrence of HIV drug resistance mutations (DRMs) in both intact and defective HIV-1 cell-associated DNA (HIV-1 CAD) among early-treated infants.

DESIGN: The Botswana EIT Study (ClinicalTrials.gov NCT02369406) initiated antiretroviral therapy (ART) in the first week of life and evaluated HIV-1 in plasma and peripheral blood mononuclear cells (PBMCs).

METHODOLOGY: We analyzed 257 near-HIV-1 full-length sequences (nFLS) obtained by Illumina next-generation sequencing from infants near birth. Sanger sequencing of pol was performed for mothers at delivery and children with clinical failure through 96 weeks. DRMs were identified using the Stanford HIV Drug Resistance Database.

RESULTS: In 27 infants, median PBMC HIV-1 proviral load was 492 copies/ml [IQR: 78-1246 copies/ml] at a median of 2 days (range 1-32); 18 (66.7%) had no DRMs detected; six (22.2%) had DRMs detected in defective DNA only, and three (11.1%) had DRMs in both defective and intact DNA (P = 0.09). A total of 60 of 151 (37.7%) defective sequences had at least one DRM: 31.8% NNRTI, 15.2% NRTI, 5.3% protease inhibitor, and 15.5% INSTI-associated mutations. In intact sequences, 33 of 106 (31.1%) had at least 1 DRM: 29.2% NNRTI, 7.5% NRTI, 0.9% protease inhibitor, and no INSTI-associated mutations. For all three infants with intact sequence DRMs, corresponding DRMs occurred in maternal plasma at delivery. Archived DRMs were detectable at a later clinical rebound on only one occasion.

CONCLUSION: Defective HIV-1 cell-associated DNA sequences may overestimate the prevalence of drug resistance among early-treated children. The impact of DRMs from intact proviruses on long-term treatment outcomes warrants further investigation.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

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