Chronic Liver Enzyme Elevation and Use of Contemporary ARVs Among People With HIV.

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.

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Déclaration de conflit d'intérêts

Potential conflict of interest. M.v.d.V. has received fees for participation in advisory boards and research grants from Gilead, MSD, and ViiV all paid to his institution. H.F.G. has received honoraria for DSMB or advisory board membership from ViiV, GSK, Merck, Gilead, Janssen, Johnson and Johnson, and Novartis. Furthermore, he has received a travel grant from Gilead. Outside of this work, he has received research grants paid to his institution from the Swiss National Science Foundation, Swiss HIV Cohort Study, NIH, Yvonne Jacob Foundation, Gilead, and ViiV. A.M. has received travel support, honoraria, and speaker fees from Gilead, ViiV, and Eiland and Bonnin, all outside the submitted work.