Objectives: Treatment failures to modern antiretroviral therapy (ART) raise concerns, as they could re-duce future options. Evaluations of occurrence of multiple failures to modern ART are missing and their significance in the long run is unclear.Methods: People with HIV (PWH) in the ICONA cohort who started a modern first-line ART were defined as 'difficult to treat' (DTT) if they experienced >= 1 among: i)>= 2 VF (2 viral loads, VL > 200 copies/mL or 1 VL > 10 0 0 copies/mL) with or without ART change; ii) >= 2 treatment discontinuations (TD) due to toxic-ity/intolerance/failure; iii) >= 1 VF followed by ART change plus >= 1 TD due to toxicity/intolerance/failure. A subgroup of the DTT participants were matched to PWH that, after the same time, were non-DTT. Treat-ment response, analysing VF, TD, treatment failure, AIDS/death, and SNAE (Serious non-AIDS event)/death, were compared. Survival analysis by KM curves and Cox regression models were employed.Results: Among 8061 PWH, 320 (4%) became DTT. Estimates of becoming DTT was 6.5% (95% CI: 5.8- 7.4%) by 6 years. DTT PWH were significantly older, with a higher prevalence of AIDS and lower CD4 + at nadir than the non-DTT. In the prospective analysis, DTT demonstrated a higher unadjusted risk for all the outcomes. Once controlled for confounders, significant associations were confirmed for VF (aHR 2.23, 1.33-3.73), treatment failure (aHR 1.70, 1.03-2.78), and SNAE/death (aHR 2.79, 1.18-6.61). Conclusion: A total of 6.5% of PWH satisfied our definition of DTT by 6 years from ART starting. This appears to be a more fragile group who may have higher risk of failure.(c) 2023 The Author(s). Published by Elsevier Ltd.

Characterization and outcomes of difficult-to-treat patients starting modern first-line ART regimens: Data from the ICONA cohort / Gagliardini, Roberta; Tavelli, Alessandro; Rusconi, Stefano; Lo Caputo, Sergio; Spagnuolo, Vincenzo; Santoro, Maria Mercedes; Costantini, Andrea; Vergori, Alessandra; Maggiolo, Franco; Giacomelli, Andrea; Burastero, Giulia; Madeddu, Giordano; Quiros Roldan, Eugenia; d'Arminio Monforte, Antonella; Antinori, Andrea; Cozzi-Lepri, Alessandro. - In: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS. - ISSN 0924-8579. - 63:1(2024), p. 107018. [10.1016/j.ijantimicag.2023.107018]

Characterization and outcomes of difficult-to-treat patients starting modern first-line ART regimens: Data from the ICONA cohort

Madeddu, Giordano;
2024-01-01

Abstract

Objectives: Treatment failures to modern antiretroviral therapy (ART) raise concerns, as they could re-duce future options. Evaluations of occurrence of multiple failures to modern ART are missing and their significance in the long run is unclear.Methods: People with HIV (PWH) in the ICONA cohort who started a modern first-line ART were defined as 'difficult to treat' (DTT) if they experienced >= 1 among: i)>= 2 VF (2 viral loads, VL > 200 copies/mL or 1 VL > 10 0 0 copies/mL) with or without ART change; ii) >= 2 treatment discontinuations (TD) due to toxic-ity/intolerance/failure; iii) >= 1 VF followed by ART change plus >= 1 TD due to toxicity/intolerance/failure. A subgroup of the DTT participants were matched to PWH that, after the same time, were non-DTT. Treat-ment response, analysing VF, TD, treatment failure, AIDS/death, and SNAE (Serious non-AIDS event)/death, were compared. Survival analysis by KM curves and Cox regression models were employed.Results: Among 8061 PWH, 320 (4%) became DTT. Estimates of becoming DTT was 6.5% (95% CI: 5.8- 7.4%) by 6 years. DTT PWH were significantly older, with a higher prevalence of AIDS and lower CD4 + at nadir than the non-DTT. In the prospective analysis, DTT demonstrated a higher unadjusted risk for all the outcomes. Once controlled for confounders, significant associations were confirmed for VF (aHR 2.23, 1.33-3.73), treatment failure (aHR 1.70, 1.03-2.78), and SNAE/death (aHR 2.79, 1.18-6.61). Conclusion: A total of 6.5% of PWH satisfied our definition of DTT by 6 years from ART starting. This appears to be a more fragile group who may have higher risk of failure.(c) 2023 The Author(s). Published by Elsevier Ltd.
2024
Characterization and outcomes of difficult-to-treat patients starting modern first-line ART regimens: Data from the ICONA cohort / Gagliardini, Roberta; Tavelli, Alessandro; Rusconi, Stefano; Lo Caputo, Sergio; Spagnuolo, Vincenzo; Santoro, Maria Mercedes; Costantini, Andrea; Vergori, Alessandra; Maggiolo, Franco; Giacomelli, Andrea; Burastero, Giulia; Madeddu, Giordano; Quiros Roldan, Eugenia; d'Arminio Monforte, Antonella; Antinori, Andrea; Cozzi-Lepri, Alessandro. - In: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS. - ISSN 0924-8579. - 63:1(2024), p. 107018. [10.1016/j.ijantimicag.2023.107018]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/324389
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