Durability and tolerability of first-line regimens including two nucleoside reverse transcriptase inhibitors and raltegravir or ritonavir boosted-atazanavir or -darunavir: data from the ICONA Cohort*

A d’Arminio Monforte, P Lorenzini, A Cozzi-Lepri, C Mussini, A Castagna, F Baldelli, M Puoti, F Vichi, A Maddaloni, S Lo Caputo, N Gianotti, A Antinori, on behalf of the Icona foundation study group

Research output: Contribution to journalArticle

Abstract

Background: We aimed to mimic the ACTG 5257 trial, comparing raltegravir (RAL), ritonavir-boosted atazavavir (ATV/r) and ritonavir-booste d darunavir (DRV/r) in the observational setting. Methods: All the ICONA patients starting a first cART with 2NRTI + ATV/r, DRV/r or RAL were included. Primary end-point was treatment failure, i.e. virological failure (confirmed HIV-RNA  >  200copies/mL  >  6 months therapy) or discontinuation for any reason of the third drug. Secondary end-points: virological failure50 (50 copies/mL threshold), and discontinuation of the third drug due to intolerance/toxicity. Cox regression analyses were run to compare the risk of outcomes between the three regimens. Results: 2249 patients were included, 985 (44%) initiated ATV/r, 1023 (45%) DRV/r and 241 (11%) RAL; median follow-up of 3.6 years (IQR: 2.3–5.2). After controlling for baseline confounding factors, patients given ATV/r showed a 26% higher risk of treatment failure (TF) vs. DRV/r (AHR 1.26, 95%CI 1.11–1.43); patients on RAL had a lower risk of TF vs. ATV/r (AHR 0.81, 95%CI 0.66–0.99). The probability of virological failure50 was significantly lower for people initiating RAL vs. DRV/r (AHR 0.46, 95%CI 0.24–0.87) or ATV/r (AHR 0.52, 95%CI 0.27–0.99). In addition, RAL was associated to a lower risk of discontinuation for toxicity vs. both DRV/r (AHR: 0.37, 95%CI: 0.19–0.72) and ATV/r (AHR: 0.18, 95%CI: 0.09–0.34). ATV/r was associated with a higher risk of discontinuing due to toxicity (AHR 2.09, 95%CI 1.63–2.67) vs. DRV/r. Conclusions: In our observational study, we confirmed higher risk of treatment failure and lower tolerability of ATV/r-based regimens as compared to those including DRV/r or RAL. © 2018 Informa UK Limited, trading as Taylor & Francis Group
Original languageEnglish
Pages (from-to)52-60
Number of pages9
JournalHIV Clinical Trials
Volume19
Issue number2
DOIs
Publication statusPublished - 2018

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Ritonavir
Reverse Transcriptase Inhibitors
Nucleosides
Treatment Failure
Atazanavir Sulfate
Raltegravir Potassium
Darunavir
Pharmaceutical Preparations
Observational Studies
Regression Analysis
HIV
RNA

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Durability and tolerability of first-line regimens including two nucleoside reverse transcriptase inhibitors and raltegravir or ritonavir boosted-atazanavir or -darunavir: data from the ICONA Cohort*. / d’Arminio Monforte, A; Lorenzini, P; Cozzi-Lepri, A; Mussini, C; Castagna, A; Baldelli, F; Puoti, M; Vichi, F; Maddaloni, A; Lo Caputo, S; Gianotti, N; Antinori, A; group, on behalf of the Icona foundation study.

In: HIV Clinical Trials, Vol. 19, No. 2, 2018, p. 52-60.

Research output: Contribution to journalArticle

d’Arminio Monforte, A, Lorenzini, P, Cozzi-Lepri, A, Mussini, C, Castagna, A, Baldelli, F, Puoti, M, Vichi, F, Maddaloni, A, Lo Caputo, S, Gianotti, N, Antinori, A & group, OBOTIFS 2018, 'Durability and tolerability of first-line regimens including two nucleoside reverse transcriptase inhibitors and raltegravir or ritonavir boosted-atazanavir or -darunavir: data from the ICONA Cohort*', HIV Clinical Trials, vol. 19, no. 2, pp. 52-60. https://doi.org/10.1080/15284336.2018.1440691
d’Arminio Monforte, A ; Lorenzini, P ; Cozzi-Lepri, A ; Mussini, C ; Castagna, A ; Baldelli, F ; Puoti, M ; Vichi, F ; Maddaloni, A ; Lo Caputo, S ; Gianotti, N ; Antinori, A ; group, on behalf of the Icona foundation study. / Durability and tolerability of first-line regimens including two nucleoside reverse transcriptase inhibitors and raltegravir or ritonavir boosted-atazanavir or -darunavir: data from the ICONA Cohort*. In: HIV Clinical Trials. 2018 ; Vol. 19, No. 2. pp. 52-60.
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abstract = "Background: We aimed to mimic the ACTG 5257 trial, comparing raltegravir (RAL), ritonavir-boosted atazavavir (ATV/r) and ritonavir-booste d darunavir (DRV/r) in the observational setting. Methods: All the ICONA patients starting a first cART with 2NRTI + ATV/r, DRV/r or RAL were included. Primary end-point was treatment failure, i.e. virological failure (confirmed HIV-RNA  >  200copies/mL  >  6 months therapy) or discontinuation for any reason of the third drug. Secondary end-points: virological failure50 (50 copies/mL threshold), and discontinuation of the third drug due to intolerance/toxicity. Cox regression analyses were run to compare the risk of outcomes between the three regimens. Results: 2249 patients were included, 985 (44{\%}) initiated ATV/r, 1023 (45{\%}) DRV/r and 241 (11{\%}) RAL; median follow-up of 3.6 years (IQR: 2.3–5.2). After controlling for baseline confounding factors, patients given ATV/r showed a 26{\%} higher risk of treatment failure (TF) vs. DRV/r (AHR 1.26, 95{\%}CI 1.11–1.43); patients on RAL had a lower risk of TF vs. ATV/r (AHR 0.81, 95{\%}CI 0.66–0.99). The probability of virological failure50 was significantly lower for people initiating RAL vs. DRV/r (AHR 0.46, 95{\%}CI 0.24–0.87) or ATV/r (AHR 0.52, 95{\%}CI 0.27–0.99). In addition, RAL was associated to a lower risk of discontinuation for toxicity vs. both DRV/r (AHR: 0.37, 95{\%}CI: 0.19–0.72) and ATV/r (AHR: 0.18, 95{\%}CI: 0.09–0.34). ATV/r was associated with a higher risk of discontinuing due to toxicity (AHR 2.09, 95{\%}CI 1.63–2.67) vs. DRV/r. Conclusions: In our observational study, we confirmed higher risk of treatment failure and lower tolerability of ATV/r-based regimens as compared to those including DRV/r or RAL. {\circledC} 2018 Informa UK Limited, trading as Taylor & Francis Group",
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T1 - Durability and tolerability of first-line regimens including two nucleoside reverse transcriptase inhibitors and raltegravir or ritonavir boosted-atazanavir or -darunavir: data from the ICONA Cohort*

AU - d’Arminio Monforte, A

AU - Lorenzini, P

AU - Cozzi-Lepri, A

AU - Mussini, C

AU - Castagna, A

AU - Baldelli, F

AU - Puoti, M

AU - Vichi, F

AU - Maddaloni, A

AU - Lo Caputo, S

AU - Gianotti, N

AU - Antinori, A

AU - group, on behalf of the Icona foundation study

PY - 2018

Y1 - 2018

N2 - Background: We aimed to mimic the ACTG 5257 trial, comparing raltegravir (RAL), ritonavir-boosted atazavavir (ATV/r) and ritonavir-booste d darunavir (DRV/r) in the observational setting. Methods: All the ICONA patients starting a first cART with 2NRTI + ATV/r, DRV/r or RAL were included. Primary end-point was treatment failure, i.e. virological failure (confirmed HIV-RNA  >  200copies/mL  >  6 months therapy) or discontinuation for any reason of the third drug. Secondary end-points: virological failure50 (50 copies/mL threshold), and discontinuation of the third drug due to intolerance/toxicity. Cox regression analyses were run to compare the risk of outcomes between the three regimens. Results: 2249 patients were included, 985 (44%) initiated ATV/r, 1023 (45%) DRV/r and 241 (11%) RAL; median follow-up of 3.6 years (IQR: 2.3–5.2). After controlling for baseline confounding factors, patients given ATV/r showed a 26% higher risk of treatment failure (TF) vs. DRV/r (AHR 1.26, 95%CI 1.11–1.43); patients on RAL had a lower risk of TF vs. ATV/r (AHR 0.81, 95%CI 0.66–0.99). The probability of virological failure50 was significantly lower for people initiating RAL vs. DRV/r (AHR 0.46, 95%CI 0.24–0.87) or ATV/r (AHR 0.52, 95%CI 0.27–0.99). In addition, RAL was associated to a lower risk of discontinuation for toxicity vs. both DRV/r (AHR: 0.37, 95%CI: 0.19–0.72) and ATV/r (AHR: 0.18, 95%CI: 0.09–0.34). ATV/r was associated with a higher risk of discontinuing due to toxicity (AHR 2.09, 95%CI 1.63–2.67) vs. DRV/r. Conclusions: In our observational study, we confirmed higher risk of treatment failure and lower tolerability of ATV/r-based regimens as compared to those including DRV/r or RAL. © 2018 Informa UK Limited, trading as Taylor & Francis Group

AB - Background: We aimed to mimic the ACTG 5257 trial, comparing raltegravir (RAL), ritonavir-boosted atazavavir (ATV/r) and ritonavir-booste d darunavir (DRV/r) in the observational setting. Methods: All the ICONA patients starting a first cART with 2NRTI + ATV/r, DRV/r or RAL were included. Primary end-point was treatment failure, i.e. virological failure (confirmed HIV-RNA  >  200copies/mL  >  6 months therapy) or discontinuation for any reason of the third drug. Secondary end-points: virological failure50 (50 copies/mL threshold), and discontinuation of the third drug due to intolerance/toxicity. Cox regression analyses were run to compare the risk of outcomes between the three regimens. Results: 2249 patients were included, 985 (44%) initiated ATV/r, 1023 (45%) DRV/r and 241 (11%) RAL; median follow-up of 3.6 years (IQR: 2.3–5.2). After controlling for baseline confounding factors, patients given ATV/r showed a 26% higher risk of treatment failure (TF) vs. DRV/r (AHR 1.26, 95%CI 1.11–1.43); patients on RAL had a lower risk of TF vs. ATV/r (AHR 0.81, 95%CI 0.66–0.99). The probability of virological failure50 was significantly lower for people initiating RAL vs. DRV/r (AHR 0.46, 95%CI 0.24–0.87) or ATV/r (AHR 0.52, 95%CI 0.27–0.99). In addition, RAL was associated to a lower risk of discontinuation for toxicity vs. both DRV/r (AHR: 0.37, 95%CI: 0.19–0.72) and ATV/r (AHR: 0.18, 95%CI: 0.09–0.34). ATV/r was associated with a higher risk of discontinuing due to toxicity (AHR 2.09, 95%CI 1.63–2.67) vs. DRV/r. Conclusions: In our observational study, we confirmed higher risk of treatment failure and lower tolerability of ATV/r-based regimens as compared to those including DRV/r or RAL. © 2018 Informa UK Limited, trading as Taylor & Francis Group

U2 - 10.1080/15284336.2018.1440691

DO - 10.1080/15284336.2018.1440691

M3 - Article

VL - 19

SP - 52

EP - 60

JO - HIV Clinical Trials

JF - HIV Clinical Trials

SN - 1528-4336

IS - 2

ER -