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Published on: April 9, 2014
Chronic Liver Enzyme Elevation and Use of Contemporary ARVs Among People With HIV
Ashley O Roen1, Lars Peters2, Gilles Wandeler3
1Institute for Global Health, University College London, London, UK.
Insights
Newer antiretroviral drugs (ARVs) show varied liver enzyme elevation risks. Non-nucleoside reverse transcriptase inhibitors and tenofovir disoproxil fumarate increase risk, while darunavir lowers it, with no cumulative effect observed.
Area of Science:
- Hepatology
- Infectious Diseases
- Pharmacology
Background:
- Chronic liver enzyme elevation (cLEE) is a known complication of older antiretroviral drugs (ARVs).
- The liver safety profile of newer ARVs, particularly regarding cLEE, remains largely uncharacterized.
Purpose of the Study:
- To investigate the incidence of cLEE associated with various newer ARVs.
- To determine if ARV exposure duration influences the risk of cLEE.
- To identify specific ARVs or ARV classes linked to increased or decreased cLEE risk.
Main Methods:
- Analysis of data from the RESPOND cohort, including individuals initiating ARVs after January 1, 2012.
- Calculation of incidence rates (IRs) for cLEE per 1000 person-years for each ARV and exposure duration.
- Utilizing Poisson regression to estimate incidence rate ratios (IRRs) and assess associations between ARVs and cLEE.
Main Results:
- A total of 1932 out of 17,106 individuals (11.3%) experienced cLEE, with an overall IR of 22.0 per 1000 person-years.
- No cumulative effect of ARV exposure duration on cLEE incidence was observed.
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs) and tenofovir disoproxil fumarate (TDF) were independently associated with increased cLEE risk, whereas darunavir (DRV) use was associated with a decreased risk.
Conclusions:
- cLEE is common, particularly within the first year of initiating new ARVs.
- No short-term liver safety concerns were identified with integrase strand transfer inhibitors (INSTIs).
- NNRTIs and TDF are associated with higher cLEE risk, while DRV is associated with a lower risk.
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.
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