Objectives: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons are due to hepatic complications. Hepatitis coinfection, antiretroviral treatment and co-occurrence of metabolic risk factors contribute to hepatic mitochondrial damage manifesting in hepatic steatosis and steatohepatitis. The aim was to assess disease- and treatment-related predictors on hepatic mitochondrial dysfunction in HIV infection by means of a new (13)C-methionine breath test (MeBT).
Patients and methods: 148 HIV positive individuals with and without antiretroviral treatment (ART) [44 therapy-naives; 89 patients on combination ART and 15 patients on structured treatment interruption (STI)] and 20 HIV-negative controls were studied prospectively by MeBT.
Results: A decay of (13)C-methionine metabolism, expressed as cumulated percentage dose recovered over 1.5h (cPDR(1.5h)), in the subgroups of treatment-naives and patients on STI compared to controls was detected (cPDR(1.5h): 3.4 +/- 1.3% and 4.0 +/- 2.4% vs. 6.3 +/- 1.2%; p<0.01). Multivariate analyses including metabolic, treatment- and disease-related variables showed that antiretroviral treatment with stavudine, didanosine or zalcitabine and treatment-naivety were best predictors of a reduced MeBT result (cPDR(1.5h)) (beta = -0.56 and -0.50, p<0.05). CD4 count had only a minor association (beta = 0.15, p<0.05). No other variable including disease and treatment duration was associated with MeBT outcome. These factors explained 39% of the variance of MeBT results (p<0.05).
Conclusions: Therapy naivety and treatment with d-drugs were the best predictors of poor MeBT outcome. MeBT may be proposed as a feasible, noninvasive diagnostic instrument for clinical assessment of hepatic mitochondrial function and early detection of drug-induced mitochondriotoxity in chronic HIV infection.