HIV-1 pretreatment drug resistance negatively impacts outcomes of first-line antiretroviral treatment.

Autor:	Hermans LE; Virology, Department of Medical Microbiology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.; Ezintsha, University of the Witwatersrand, Johannesburg.; Ndlovu Research Consortium, Elandsdoorn, South Africa., Hofstra LM; Virology, Department of Medical Microbiology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands., Schuurman R; Virology, Department of Medical Microbiology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands., Ter Heine R; Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Burger DM; Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Talboom SAJ; Radboud University Medical Center, Nijmegen, The Netherlands., De Jong D; Virology, Department of Medical Microbiology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands., Tempelman HA; Ezintsha, University of the Witwatersrand, Johannesburg.; Ndlovu Research Consortium, Elandsdoorn, South Africa., Venter WDF; Ezintsha, University of the Witwatersrand, Johannesburg.; Ndlovu Research Consortium, Elandsdoorn, South Africa., Nijhuis M; Virology, Department of Medical Microbiology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.; Ndlovu Research Consortium, Elandsdoorn, South Africa.; HIV Pathogenesis Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa., Wensing AMJ; Virology, Department of Medical Microbiology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.; Ezintsha, University of the Witwatersrand, Johannesburg.; Ndlovu Research Consortium, Elandsdoorn, South Africa.
Jazyk:	angličtina
Zdroj:	AIDS (London, England) [AIDS] 2022 Jun 01; Vol. 36 (7), pp. 923-931. Date of Electronic Publication: 2022 Feb 01.
DOI:	10.1097/QAD.0000000000003182
Abstrakt:	Introduction: Pretreatment drug resistance (PDR) prevalence in sub-Saharan Africa is rising, but evidence of its impact on efavirenz (EFV)-based antiretroviral treatment (ART) is inconclusive. We determined the impact of PDR on outcomes of EFV-based ART in a subanalysis of a randomized clinical trial comparing different ART monitoring strategies implemented at a rural treatment facility in Limpopo, South Africa. Methods: Participants initiating EFV-based first-line ART (2015-2017) were enrolled and received 96 weeks follow-up. Resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and non-NRTI's (NNRTIs) was retrospectively assessed by population-based sequencing. Virological failure was defined as a viral load of at least 1000 copies/ml after at least 24 weeks of ART. Results: A total of 207 participants were included, 60.4% (125/207) of whom were female. Median age was 38.8 (interquartile range: 31.4-46.7) years. Median CD4+ cell count was 191 (interquartile range: 70-355) cells/μl. PDR was detected in 12.9% (25/194) of participants with available sequencing results; 19 had NNRTI-resistance, and six had NRTI- and NNRTI-resistance. 26.0% of participants (40/154) with sequencing results and virological follow-up developed virological failure. PDR was independently associated with failure (adjusted hazard ratio: 3.7 [95% confidence interval: 1.68.5], P = 0.002). At failure, 87.5% (7/8) of participants with PDR harboured dual-class resistant virus, versus 16.7% (4/24) of participants without PDR (P = 0.0007). Virological resuppression after failure on first-line ART occurred in 57.7% (15/26) of participants without PDR versus 14.3% (1/7) of participants with PDR (P = 0.09). Conclusion: PDR was detected in 13% of study participants. PDR significantly increased the risk of virological failure of EFV-based ART. Accumulation of resistance at failure and inability to achieve virological resuppression illustrates the profound impact of PDR on treatment outcomes. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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