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Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study.

Abstract

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.

Authors+Show Affiliations

Department of Medical Biotechnologies, University of Siena, Viale Bracci, 16, Siena, Italy.Department of Medical Biotechnologies, University of Siena, Viale Bracci, 16, Siena, Italy. Infectious Diseases Unit, AOU Senese, Viale Bracci, 16, Siena, Italy.National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Via Portuense, 292, Rome, Italy.National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Via Portuense, 292, Rome, Italy.InformaPRO, via Guido Guinizelli, 98/100, Rome, Italy.University of Milan, Pediatric Clinical Research Center 'Romeo and Enrica Invernizzi', Via Giovanni Battista Grassi, 74, Milan, Italy.Infectious Diseases Unit, Ospedali Riuniti, Largo Barozzi, 1, Bergamo, Italy.UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, Roma, Italia.UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, Roma, Italia.UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, Roma, Italia.Microbiology and Virology Unit, Bergamo Hospital, Piazza OMS, 1, Bergamo, Italy.Microbiology Unit, Ospedale L. Sacco, Via G.B Grassi, 74, 20157, Milan, Italy.San Gallicano Dermatologic Institute, STI/HIV Unit, IRCCS, via Elio Chianesi, 53, Rome, Italy.Department di Clinical and Experimental Medicine, Clinic of Tropical and Infectious Diseases, University of Florence, Largo Brambilla, 3, 50134, Florence, Italy.Clinical Immunology Unit, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Via Tronto, 10, 60121, Ancona, Italy.Clinic of Infectious Diseases, Azienda ospedaliera-Universitaria Ospedali Riuniti, Viale Luigi Pinto, 1, 71122, Foggia, Italy.Infectious and Tropical Diseases Unit, DIBIC L. Sacco Hospital, University of Milano, Via G.B Grassi, 74, 20157, Milan, Italy.Department of Medical Biotechnologies, University of Siena, Viale Bracci, 16, Siena, Italy.Infectious Diseases Unit, AOU Senese, Viale Bracci, 16, Siena, Italy.Department of Medical Biotechnologies, University of Siena, Viale Bracci, 16, Siena, Italy. Infectious Diseases Unit, AOU Senese, Viale Bracci, 16, Siena, Italy.Infectious Diseases, IRCCS San Raffaele, Via Olgettina 60, Milan, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31605107

Citation

Modica, Sara, et al. "Impact of NRTI Resistance Mutations On Virological Effectiveness of Antiretroviral Regimens Containing Elvitegravir: a Multi-cohort Study." The Journal of Antimicrobial Chemotherapy, 2019.
Modica S, Redi D, Gagliardini R, et al. Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study. J Antimicrob Chemother. 2019.
Modica, S., Redi, D., Gagliardini, R., Giombini, E., Bezenchek, A., Di Carlo, D., ... Gianotti, N. (2019). Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study. The Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkz424.
Modica S, et al. Impact of NRTI Resistance Mutations On Virological Effectiveness of Antiretroviral Regimens Containing Elvitegravir: a Multi-cohort Study. J Antimicrob Chemother. 2019 Oct 11; PubMed PMID: 31605107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study. AU - Modica,Sara, AU - Redi,David, AU - Gagliardini,Roberta, AU - Giombini,Emanuela, AU - Bezenchek,Antonia, AU - Di Carlo,Domenico, AU - Maggiolo,Franco, AU - Lombardi,Francesca, AU - Borghetti,Alberto, AU - Farinacci,Damiano, AU - Callegaro,Annapaola, AU - Gismondo,Maria R, AU - Colafigli,Manuela, AU - Sterrantino,Gaetana, AU - Costantini,Andrea, AU - Ferrara,Sergio M, AU - Rusconi,Stefano, AU - Zazzi,Maurizio, AU - Rossetti,Barbara, AU - De Luca,Andrea, AU - Gianotti,Nicola, Y1 - 2019/10/11/ PY - 2019/05/08/received PY - 2019/09/04/revised PY - 2019/09/10/accepted PY - 2019/10/13/entrez JF - The Journal of antimicrobial chemotherapy JO - J. Antimicrob. Chemother. N2 - 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. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/31605107/Impact_of_NRTI_resistance_mutations_on_virological_effectiveness_of_antiretroviral_regimens_containing_elvitegravir:_a_multi-cohort_study L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkz424 DB - PRIME DP - Unbound Medicine ER -