Visceral fat reduction with tesamorelin is associated with improved liver enzymes in HIV

Abstract

Objective: Tesamorelin reduces visceral adipose tissue (VAT) in HIV. We investigated whether reductions in VAT with tesamorelin are associated with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Design and methods: We utilized data from two multicenter Phase III trials of tesamorelin among 806 HIV-infected patients with abdominal obesity. These studies showed that the majority of patients treated with tesamorelin are 'responders', defined a priori by the Food and Drug Administration as achieving at least 8% reduction in VAT. In the current analysis, we sought to examine the impact of VAT reduction on ALT and AST among patients participating in the Phase III trials with baseline elevated ALT or AST. Within this group, we compared changes in ALT and AST in VAT responders vs. nonresponders after 26 weeks of treatment, and then assessed the effects of drug discontinuation on these endpoints over a subsequent 26-week period.

Results: At baseline, VAT was positively associated with ALT (P = 0.01). In study participants assigned to tesamorelin with baseline ALT or AST more than 30 U/l, VAT responders experienced greater reductions in ALT (-8.9 ± 22.6 vs. 1.4 ± 34.7 U/l, P = 0.004) and AST (-3.8 ± 12.9 vs. 0.4 ± 22.4 U/l, P = 0.04) compared with nonresponders over 26 weeks. This improvement among VAT responders persisted over 52 weeks even in those switched to placebo despite a partial reaccumulation of VAT.

Conclusion: A clinically significant VAT reduction with tesamorelin was associated with improved liver enzymes among HIV-infected patients with abdominal obesity and elevated baseline transaminases.

Trial registration: ClinicalTrials.gov NCT00123253 NCT00435136 NCT00608023.

Conflict of interest statement

Conflicts of Interest: L.T.F., N.C., M.N.F., and J.W. have nothing to disclose.

Figures

Figure 1. Analysis schema

T-T, tesamorelin responders at week 26 assigned to continue tesamorelin for an additional 26 weeks. T-P, tesamorelin responders at week 26 switched to placebo for 26 weeks.

Figure 2. Changes in ALT and AST among tesamorelin VAT responders and nonresponders with baseline ALT or AST > 30 U/L at week 26

P-values are based on comparisons of responders and nonresponders adjusting for baseline ALT or AST, clinical trial, and viral hepatitis status. Responder × hepatitis and responder × trial interactions were not significant. Error bars represent the standard error of the mean.

Figure 3. Changes among initial tesamorelin VAT responders with baseline ALT or AST > 30 U/L following re-randomization to tesamorelin (T-T) or placebo (T-P) at week 52

P-values shown reflect comparisons of T-T and T-P groups controlling for baseline value, change from baseline to week 26, and clinical trial. Results of within-group comparisons of liver enzymes between week 52 and baseline are designated as * P < 0.001, § P < 0.05. Error bars represent the standard error of the mean.