2025
| 8th January | Roen et al., cLEE and use of contemporary ARVs among PWH |  |
Roen et al. on behalf of the RESPOND consortium aimed to identify risk factors associated with chronic liver enzyme (transaminase) elevation (cLEE), focusing on commonly prescribed antiretrovirals (ARVs) in RESPOND, namely INSTIs (dolutegravir [DTG], raltegravir [RAL], cobicistat boosted elvitegravir [EVG/c], and bictegravir [BIC]), protease inhibitors (PIs; boosted darunavir [DRV/b] and atazanavir [ATV/b]), non-nucleoside reverse transcriptase inhibitors (NNRTIs; rilpivirine [RPV] and efavirenz [EFV]), and backbone nucleoside reverse transcriptase inhibitors (NRTIs) that have been associated with liver impairment (tenofovir disoproxil fumarate [TDF]) and ALT normalization (tenofovir alafenamide [TAF]). People with HIV enrolled in the RESPOND cohort who started an ARV after January 1, 2012 were included (baseline). 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). Of 17’106 individuals included contributing 87’924 person-years of follow-up, 1’932 (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. In conclusion, the author team analyzed a large observational study and systematically examined the relationship between commonly used ARVs and chronic liver injury, assessed using liver enzymes, and found no short-term safety concerns with the use of INSTIs. The study found an elevated risk of cLEE with use of NNRTIs (driven by EFV, RPV) and TDF, a decreased risk of cLEE with DRV/b use, and a nonsignificant trend toward decreased risk of cLEE with TAF. Further research is needed to monitor longer-term associations with cLEE, particularly for INSTIs, associations with other liver end points including markers of fibrosis, and the impact of cLEE on mortality for newer ARVs in different settings. | ||