Effects of antioxidant supplementation on liver fibrosis in HIV+ individuals on Antiretroviral Therapy (ART) in the Miami Adult Studies in HIV (MASH) cohort
Authors: Hernandez Jacqueline , Mugdal Mukesh , Stewart Tiffanie , Campa Adriana , Martinez Sabrina Sales , Li Qingyun , Baum Marianna K 
Published: November 2023

BackgroundLiver disease is one of the major causes of death in people living with HIV (PLWH), increasing the risk of mortality by 85% (Kitahata, NEJM 2009). While ART minimizes the effect of HIV, PLWH continue to have increased prevalence of liver disease morbidity (Blackard, CID 2011). Studies of pathophysiological mechanisms show that oxidative stress is a key feature of the cytotoxic effect of HIV in many organs, including the liver (Lin, J Biol Chem 2011). The objective of this pilot study was to examine the effects of antioxidant supplementation on liver fibrosis over 12 weeks.MethodsParticipants were selected from the Miami Adult Studies in HIV (MASH) cohort and were randomly assigned into the intervention (N=12) and control groups (N=13) for 12 weeks. All participants were on stable ART with undetectable HIV viral load. The intervention group was supplemented with multivitamins (Centrum®), 500 mg alpha‐lipoic acid, 1,200 mg N‐acetyl‐cysteine, and 1,000 mg acetyl‐L‐carnitine for 12 weeks. The control group received placebo. Non‐invasive markers of liver fibrosis were used: FIB‐4 score (age (years)x AST (U/L)]/[PLT (109 cells/L)xALT1/2 (U/L)] and APRI: [AST(x upper limit of normal range) × 100]/platelet count (109 cells/L). Liver enzymes levels, AST, ALT, and platelets were obtained from the metabolic panel and CD4 count and HIV viral load from the medical charts. Descriptive statistics, T‐tests and linear regression models were used to analyze the data using age and gender as covariates.ResultsThe control group's mean age was 48±5 years and 62% were males. The intervention group's mean age was 50±5 years and 58% were males. As expected, for the period of 12 weeks, the antioxidant supplementation did not improve FIB‐4 and APRI scores in the intervention group. However, from baseline to one year, the intervention group improved FIB‐4 score from 1.31±0.42 at baseline to 1.08±0.42 at one year, while the control group increased FIB‐4 from 1.17±0.36 at baseline to 1.26±0.41 at one year, indicating progression of liver disease. The change over time in FIB‐4 was statistically significant between the intervention and control groups (−0.16±0.28 vs. 0.17±0.21, p=0.014). The change in the APRI score was also significantly different at one year between the intervention and control groups (−0.03±0.05 vs. 0.03±0.05, p=0.019). The groups were not different from each other in liver enzyme levels at 12 weeks or at 1 year.ConclusionAntioxidant supplementation for 12 weeks significantly improved liver fibrosis in one year in PLWH on stable ART and undetectable HIV viral load. Although the antioxidant supplementation study lasted only 12 weeks, there was a residual effect observed for one year on liver fibrosis as measured by FIB‐4 and APRI scores. This pilot study indicated the need for larger longitudinal studies supplementing antioxidants in PLWH on ART to demonstrate the effects of antioxidants as a promising therapy in improving liver fibrosis.Support or Funding InformationNIDA