Chronic Liver Enzyme Elevation and Use of Contemporary ARVs Among People With HIV
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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | ofae308 |
| Tidsskrift | Open Forum Infectious Diseases |
| Vol/bind | 11 |
| Udgave nummer | 6 |
| Antal sider | 14 |
| ISSN | 2328-8957 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
Previous observational data from the D:A:D and Swiss HIV Cohort Studies have also shown an association between TDF and elevated ALT levels in those with and without viral hepatitis coinfection [, ], consistent with our findings. We found a trend for slightly reduced risk of cLEE with TAF, although this did not reach statistical significance. This is supported by data from the Swiss HIV Cohort Study and the Canadian Hepatitis B Network showing that among those with elevated ALT, switching from TDF to TAF significantly reduces ALT elevations [, ]. It is worth noting that in RESPOND there is likely confounding by indication with TAF utilization given that it has a more favorable safety profile compared with TDF.
Funding Information:
The International Cohort Consortium of Infectious Disease (RESPOND) has received funding from ViiV Healthcare LLC, Gilead Sciences, and Merck Sharp & Dohme. Additional support has been provided by participating cohorts contributing data in-kind and/or statistical support: Austrian HIV Cohort Study (AHIVCOS), The Australian HIV Observational Database (AHOD), CHU Saint-Pierre, University Hospital Cologne, EuroSIDA, Frankfurt HIV Cohort Study, Georgian National AIDS Health Information System (AIDS HIS), Modena HIV Cohort, San Raffaele Scientific Institute, Swiss HIV Cohort Study (SHCS), AIDS Therapy Evaluation in the Netherlands Cohort (ATHENA), Royal Free HIV Cohort Study. A.H.O.D. is further supported by grant No. U01-AI069907 from the US National Institutes of Health and GNT1050874 from the National Health and Medical Research Council, Australia.
Funding Information:
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.
Funding Information:
Financial support. The International Cohort Consortium of Infectious Disease (RESPOND) has received funding from ViiV Healthcare LLC, Gilead Sciences, and Merck Sharp & Dohme. Additional support has been provided by participating cohorts contributing data in-kind and/or statistical support: Austrian HIV Cohort Study (AHIVCOS), The Australian HIV Observational Database (AHOD), CHU Saint-Pierre, University Hospital Cologne, EuroSIDA, Frankfurt HIV Cohort Study, Georgian National AIDS Health Information System (AIDS HIS), Modena HIV Cohort, San Raffaele Scientific Institute, Swiss HIV Cohort Study (SHCS), AIDS Therapy Evaluation in the Netherlands Cohort (ATHENA), Royal Free HIV Cohort Study. A.H.O.D. is further supported by grant No. U01-AI069907 from the US National Institutes of Health and GNT1050874 from the National Health and Medical Research Council, Australia.
Publisher Copyright:
© The Author(s) 2024.
ID: 399159820