BACKGROUND: Antiretroviral drug resistance mutations remain a major cause of treatment failure. OBJECTIVES: To evaluate the impact of NRTI resistance mutations on virological effectiveness of elvitegravir-containing regimens. MATERIALS AND METHODS: We selected treatment-experienced HIV-1-infected patients starting elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), with at least one protease/reverse transcriptase genotype available before switching and at least one HIV-1 RNA viral load (VL) measurement during follow-up. The primary endpoint was virological failure (VF), defined as one VL value of ≥1000 copies/mL or two consecutive VL values of >50 copies/mL. RESULTS: We included 264 ART regimens: 75.6% male, median (IQR) age 47 years (39-53), 7 years (3-16) of HIV infection, nadir CD4+ 247 cells/mm3 (105-361), 81.5% with VL ≤50 copies/mL and 11.7% with at least one NRTI mutation at baseline. Eleven (5.2%) VFs occurred in virologically suppressed patients versus eight (15.1%) in viraemic patients. The estimated probability of VF at 48 weeks with versus without any NRTI mutation was 7.4% (95% CI 2.3-12.5) versus 3.8% (2.1-5.5) in virologically suppressed patients and 66.7% (39.5-93.9) versus 11.2% (6.5-15.9) (P<0.001) in viraemic patients. The only predictor of VF was time on therapy (per 1 year more, adjusted HR 1.14, 95% CI 1.02-1.27, P=0.024) in viraemic patients. CONCLUSIONS: A switch to E/C/F/TDF or E/C/F/TAF is safe for virologically suppressed patients without documented NRTI resistance, but not recommended in viraemic patients with a history of NRTI resistance. Although we did not detect a detrimental effect of past NRTI resistance in virologically suppressed patients, a fully active regimen remains preferred in this setting due to possible rebound of drug-resistant virus in the long term.
Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir : a multi-cohort study / S. Modica, D. Redi, R. Gagliardini, E. Giombini, A. Bezenchek, D. Di Carlo, F. Maggiolo, F. Lombardi, A. Borghetti, D. Farinacci, A. Callegaro, M.R. Gismondo, M. Colafigli, G. Sterrantino, A. Costantini, S.M. Ferrara, S. Rusconi, M. Zazzi, B. Rossetti, A. De Luca, N. Gianotti. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 0305-7453. - 75:1(2020 Jan 01), pp. 194-199.
|Titolo:||Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir : a multi-cohort study|
|Settore Scientifico Disciplinare:||Settore MED/17 - Malattie Infettive|
|Data di pubblicazione:||1-gen-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/jac/dkz424|
|Appare nelle tipologie:||01 - Articolo su periodico|
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