RESUMO
Background: While use of some older antiretroviral drugs (ARVs) is associated with chronic liver enzyme elevation (cLEE), the impact of newer ARVs remains unknown. Methods: People with HIV enrolled in the RESPOND cohort who started an ARV after January 1, 2012 were included (baseline). The primary outcome was first cLEE individuals were censored at first of cLEE, last visit, death, or December 31, 2021. Incidence rates (IRs; events/1000 person-years) were calculated for each ARV overall and by ARV exposure (6-12 months, 1-2 years, and 2+ years). Poisson regression was used to estimate the incidence rate ratio (IRR) of cLEE and its association with individual ARVs and ARV class. Results: Of 17 106 individuals included contributing 87 924 person-years of follow-up, 1932 (11.3%) experienced cLEE (incidence rate [IR], 22.0; 95% CI, 21.0-23.0). There was no evidence of a cumulative ARV effect on cLEE incidence, (6-12 months: IR, 45.8; 95% CI, 41.4-50.19; 1-2 years: IR, 34.3; 95% CI, 31.5-37.4; and 2+ years: IR, 18.5; 95% CI, 17.4-19.7). Any use (vs no prior use) of non-nucleoside reverse transcriptase inhibitors (NNRTIs) as a class and tenofovir disoproxil fumarate (TDF) was independently associated with an increased IRR of cLEE, and any use of darunavir (DRV) was associated with a decreased risk of cLEE. Conclusions: cLEE is common and more frequent during the first year after initiating new ARVs. With a >5-year median follow-up, we found no short-term liver safety concerns with the use of INSTIs. Use of NNRTIs and TDF was associated with an increased cLEE risk, while DRV was associated with lower risk.
RESUMO
AIM: Remdesivir (RDV) causes liver enzyme elevation in adults; however, the frequency of this elevation in children and the associated risk factors are largely unknown. Therefore, we aimed to examine risk factors for liver enzyme elevation in hospitalised paediatric patients who received RDV. METHODS: This was a retrospective case-control study of all patients aged <18 years who were diagnosed with coronavirus disease 2019 and received RDV at a tertiary care hospital between February 2022 and September 2023. Demographic and clinical data were retrieved from the medical records and analysed. Patients with liver enzyme elevation were defined as cases, while those with no liver enzyme elevation were defined as controls. The two groups were compared and analysed for possible risk factors for liver enzyme elevation with RDV use. RESULTS: Sixty-six patients were treated with RDV, 12 (18.2%) of whom developed liver enzyme elevation. Liver enzyme elevation was associated with the median duration of RDV administration (7.5 days vs. 3 days, P = 0.012), median total RDV dose (17.7 mg/kg vs. 10.3 mg/kg, P = 0.017) and acetaminophen use (67% vs. 22%) (odds ratio = 4.34; 95% confidence interval, 1.05-19.97, P = 0.023). All patients showed improvement, except three who had no liver enzyme measurements after having the highest aspartate aminotransferase and alanine aminotransferase values during the observation period. CONCLUSION: Liver enzyme elevation was reversible after discontinuing RDV use. Overall, RDV can be considered safe in children with careful monitoring.