Borghetti, A., Ciccullo, A., Lombardi, F., Baldin, G., Belmonti, S., Prosperi, M., Incardona, F., Heger, E., Borghi, V, Sonnerborg, A., Zazzi, M., De Luca, A. and Di Giambenedetto, S. (2021). Transmitted drug resistance to NRTIs and risk of virological failure in naive patients treated with integrase inhibitors. HIV Med., 22 (1). S. 22 - 28. HOBOKEN: WILEY. ISSN 1468-1293

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Abstract

Objectives Nucleoside reverse transcriptase inhibitor (NRTI) transmitted drug resistance mutations (TDRMs) could increase the risk of virological failure (VF) of first-line integrase strand transfer inhibitor (InSTI)-based regimens. Methods Patients starting two NRTIs (lamivudine/emtricitabine plus abacavir/tenofovir) plus raltegravir or dolutegravir were selected from the EuResist cohort. The role of NRTI genotypic susceptibility score and of specific TDRMs in VF (i.e. two consecutive viral loads > 50 HIV-1 RNA copies/mL or a single viral load >= 200 copies/mL after 3 months from antiretroviral therapy start) was evaluated in the overall population and according to the InSTI employed. Results From 2008 to 2017, 1095 patients were eligible for the analysis (55.5% men, median age 39 years). In all, 207 VFs occurred over 1023 patient-years of follow-up. The genotypic susceptibility score (GSS) had no effect on the risk of VF in the overall population. However, the presence of M184V/I independently predicted VF of raltegravir- but not dolutegravir-based therapy when compared with a fully-active backbone [adjusted hazard ratio (aHR) = 3.09,P = 0.035], particularly when associated with other non-thymidine analogue mutations (aHR = 27.62,P = 0.004). Higher-zenith HIV-RNA and lower nadir CD4 counts independently predicted VF. Conclusions NRTI backbone TDRMs increased the risk of VF with raltegravir-based but not dolutegravir-based regimens.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Borghetti, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ciccullo, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lombardi, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baldin, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belmonti, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prosperi, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Incardona, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heger, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borghi, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sonnerborg, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zazzi, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Luca, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Di Giambenedetto, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-318510
DOI: 10.1111/hiv.12956
Journal or Publication Title: HIV Med.
Volume: 22
Number: 1
Page Range: S. 22 - 28
Date: 2021
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1468-1293
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Infectious DiseasesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31851

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