TY - JOUR
T1 - Overall Tolerability of Integrase Inhibitors in Clinical Practice: Results from a Multicenter Italian Cohort
AU - Ciccullo, Arturo
AU - Baldin, Gianmaria
AU - Borghi, Vanni
AU - Sterrantino, Gaetana
AU - Madeddu, Giordano
AU - Latini, Alessandra
AU - D'Ettorre, Gabriella
AU - Lanari, Alessandro
AU - Mazzitelli, Maria
AU - Colafigli, Manuela
AU - Capetti, Amedeo Ferdinando
AU - Oreni, Letizia
AU - Lagi, Filippo
AU - Rusconi, Stefano
AU - Di Giambenedetto, Simona
PY - 2021
Y1 - 2021
N2 - International guidelines recommend the use of integrase strand transfer inhibitor (INI)-based regimens as first-line antiretroviral (ARV) in both naive and experienced HIV-infected patients. We analyzed a multicenter cohort of HIV-infected patients, both naive and experienced, starting an ARV, including an INI. Chi-square test and nonparametric tests were used to assess differences in categorical and continuous variables, respectively. Kaplan-Meier survival analysis was performed to estimate the probability of maintaining the study drug and Cox-regression analysis to evaluate predictors of discontinuation. We enrolled 4,343 patients: 3,143 (72.4%) were males, with a median age of 49 years (interquartile range 41-55). Naive patients were 733 (16.9%), of whom 168 (22.9%) were AIDS presenters. Overall, 2,282 patients (52.5%) started dolutegravir (DTG), 1,426 (32.8%) raltegravir (RAL), and 635 (14.7%) elvitegravir (EVG). During 10,032 patient years of follow-up (PYFU), we observed 1,278 discontinuations (13 per 100 PYFU); 448 of them (35%) due to simplification and 355 (28%) to toxicities (98 for central nervous system toxicity). Reasons of discontinuation were different between INIs. Estimated probability of maintaining DTG at 3 and 4 years were 81.5% [95% confidence interval (CI): 80.5-82.5] and 76.3% (95% CI: 73.9-78.7), respectively; RAL 61.6% (95% CI: 60.2-63.0) and 54.1% (95% CI: 52.7-55.5); EVG 71.6% (95% CI: 69.2-74.0) and 68.3% (95% CI: 65.3-71.3) (p < .001). At a multivariable analysis, being on a RAL-based ARV [vs. DTG, adjusted hazard ratio (aHR) 2.9, 95% CI: 2.3-3.6, p < .001], a EVG-based ARV (vs. DTG, aHR 1.3 95% CI: 1.1-1.7, p = .049), and a peak HIV-RNA >500k cp/mL (aHR 1.3, 95% CI: 1.1-1.6, p = .006) predicted INI discontinuation. Our data confirm the good tolerability of INIs in clinical practice. Differences emerge between the three drugs in reasons for discontinuation.
AB - International guidelines recommend the use of integrase strand transfer inhibitor (INI)-based regimens as first-line antiretroviral (ARV) in both naive and experienced HIV-infected patients. We analyzed a multicenter cohort of HIV-infected patients, both naive and experienced, starting an ARV, including an INI. Chi-square test and nonparametric tests were used to assess differences in categorical and continuous variables, respectively. Kaplan-Meier survival analysis was performed to estimate the probability of maintaining the study drug and Cox-regression analysis to evaluate predictors of discontinuation. We enrolled 4,343 patients: 3,143 (72.4%) were males, with a median age of 49 years (interquartile range 41-55). Naive patients were 733 (16.9%), of whom 168 (22.9%) were AIDS presenters. Overall, 2,282 patients (52.5%) started dolutegravir (DTG), 1,426 (32.8%) raltegravir (RAL), and 635 (14.7%) elvitegravir (EVG). During 10,032 patient years of follow-up (PYFU), we observed 1,278 discontinuations (13 per 100 PYFU); 448 of them (35%) due to simplification and 355 (28%) to toxicities (98 for central nervous system toxicity). Reasons of discontinuation were different between INIs. Estimated probability of maintaining DTG at 3 and 4 years were 81.5% [95% confidence interval (CI): 80.5-82.5] and 76.3% (95% CI: 73.9-78.7), respectively; RAL 61.6% (95% CI: 60.2-63.0) and 54.1% (95% CI: 52.7-55.5); EVG 71.6% (95% CI: 69.2-74.0) and 68.3% (95% CI: 65.3-71.3) (p < .001). At a multivariable analysis, being on a RAL-based ARV [vs. DTG, adjusted hazard ratio (aHR) 2.9, 95% CI: 2.3-3.6, p < .001], a EVG-based ARV (vs. DTG, aHR 1.3 95% CI: 1.1-1.7, p = .049), and a peak HIV-RNA >500k cp/mL (aHR 1.3, 95% CI: 1.1-1.6, p = .006) predicted INI discontinuation. Our data confirm the good tolerability of INIs in clinical practice. Differences emerge between the three drugs in reasons for discontinuation.
KW - HIV
KW - HIV Infections
KW - HIV Integrase Inhibitors
KW - Heterocyclic Compounds, 3-Ring
KW - Humans
KW - Italy
KW - Male
KW - Middle Aged
KW - Oxazines
KW - Piperazines
KW - Raltegravir Potassium
KW - dolutegravir
KW - durability
KW - elvitegravir
KW - integrase inhibitors
KW - raltegravir
KW - HIV
KW - HIV Infections
KW - HIV Integrase Inhibitors
KW - Heterocyclic Compounds, 3-Ring
KW - Humans
KW - Italy
KW - Male
KW - Middle Aged
KW - Oxazines
KW - Piperazines
KW - Raltegravir Potassium
KW - dolutegravir
KW - durability
KW - elvitegravir
KW - integrase inhibitors
KW - raltegravir
UR - http://hdl.handle.net/10807/193242
U2 - 10.1089/aid.2020.0078
DO - 10.1089/aid.2020.0078
M3 - Article
SN - 0889-2229
VL - 37
SP - 4
EP - 10
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
ER -