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  • Bonfanti, P  (2)
  • Pharmacy  (2)
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  • Pharmacy  (2)
  • 1
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 74, No. 11 ( 2019-11-01), p. 3295-3304
    Abstract: To evaluate the incidence and risk factors for liver enzyme elevations (LEE) in patients initiating first-line ART in the ICONA prospective observational cohort, between June 2009 and December 2017. Patients and methods In total, 6575 ART-naive patients were selected, initiating two NRTIs with the third drug being a boosted PI (n=2436; 37.0%), an NNRTI (n=2384; 36.3%) or an integrase strand transfer inhibitor (INSTI) (n=1755; 26.7%). HBV surface antigen and HCV RNA were detected in 3.9% and 5.8% of the study population. Inverse probability weighted Cox regression analysis was used to calculate the HRs, according to first-line regimen, for LEE, defined as ALT or AST increases of ≥2.5× upper limit of normal (ULN) for patients with normal baseline values or ≥2.5× baseline for patients with higher baseline values. Results One hundred and eighty-three LEE occurred over 20722 patient-years of follow-up. After adjusting for the main confounders, the risk of LEE halved with INSTIs compared with NNRTIs (HR 0.46, 95% CI 0.25–0.86), with a significant reduction in the raltegravir group (HR 0.11, 95% CI 0.02–0.84 using the NNRTI class as reference). HRs for LEE were significantly higher in subjects with HBV or HCV coinfection, in patients with poorly controlled HIV infection and in those who acquired HIV through homosexual transmission. Conclusions In our study, INSTI use almost halved the risk of LEE compared with other regimens. This finding could be particularly important for choosing ART in patients with risk factors for liver toxicity such as HCV and HBV coinfections.
    Type of Medium: Online Resource
    ISSN: 0305-7453 , 1460-2091
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1467478-6
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 2
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 78, No. 4 ( 2023-04-03), p. 933-945
    Abstract: To compare the long-term risk of treatment failure of dolutegravir-based ART in men and women in a real-life setting. Patients and methods Persons living with HIV (PLWH) from the ICONA cohort were included if they had started dolutegravir in a two- or three-drug regimen as ART-naive or as virologically controlled ART-experienced. The primary endpoint was time to treatment failure (virological/clinical failure or dolutegravir discontinuation). Secondary endpoints were: time to dolutegravir discontinuation due to toxicity and to neuropsychiatric adverse events; and time to virological failure. Cox regression analyses focused on differences in outcomes by sex. Results A total of 2304 PLWH (15% women) initiated dolutegravir-based therapy from ART-naive, and 1916 (19.8% women) while experienced. After a median follow-up of 2.2 (IQR: 0.9–3.9) years in ART-naive and 2.4 (IQR: 1.1–4.3) years in experienced, the 4-year cumulative probability of treatment failure was 33% (95% CI 30.5–35.1) and 20% (95% CI 17.8–22.3), respectively. In the multivariable analyses, in ART-naive the risk of treatment failure was higher for women, but not different after excluding women discontinuing dolutegravir for pregnancy concerns. We also observed a higher risk of discontinuation for toxicity in women (ART-naives: Adjusted Hazard Ratio (AHR): 1.56%; 95% CI: 1.03–2.37; ART-experienced: AHR: 1.53%; 95% CI: 1.01–2.32), although the absolute 4-year probability was low: 7.7% (95% CI 6.5–9.2) in ART-naive and 8.3% (95% CI 6.9–9.9) in experienced. Conclusions In our cohort of PLWH treated with dolutegravir-based regimens and followed up for up to 4 years, we observed a low risk of treatment failure and no evidence for a difference by sex, after excluding discontinuation due to pregnancy concerns. However, we observed a higher risk of dolutegravir discontinuation for toxicity in women.
    Type of Medium: Online Resource
    ISSN: 0305-7453 , 1460-2091
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1467478-6
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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