Dietary regimens appear to possess significant effects on the development of combined antiretroviral therapy (cART)-associated metabolic syndrome

Abstract

Introduction This study investigated the interactions between a low protein high calorie (LPHC) diet and

an integrase inhibitor-containing antiretroviral drug regimen (INI-CR)in light of evidence sug- gesting that the initiation of cART in patients with poor nutritional status is a predictor of mor- tality independent of immune status.

Methods Freshly weaned Sprague Dawley rats (120) were randomized into the standard, LPHC and

normal protein high calorie (NPHC) diet groups (n = 40/group) initially for 15 weeks. Thereaf- ter, experimental animals in each diet group were further randomized into four treatment

sub-groups (n = 10/group) Control (normal saline), group 1(TDF+3TC+DTG and Tesamore- lin), group 2 (TDF+3TC+DTG), and Positive control (AZT+3TC+ATV/r) with treatment and

diets combined for 9 weeks. Weekly body weights, fasting blood glucose (FBG), oral glu- cose tolerance test (OGTT); lipid profiles, liver weights, hepatic triglycerides and adiposity

were assessed at week 24.

Results At week 15, body weights increased between the diet group in phase 1(standard 146 ± 1.64 vs. 273.1 ± 1.56 g), (NPHC, 143.5 ± 2.40 vs. 390.2 ± 4.94 g) and (LPHC, 145.5 ± 2.28 g vs. 398.3 ± 4.89 g) (p< 0.0001). A similar increase was noted in the FBG and OGTT (p< 0.0001). In phase 2, there was an increase in FBG, OGTT, body weights, lipid profile, liver weights, hepatic triglycerides, adiposity and insulin levels in group 2 and positive control in both NPHC and LPHC diet groups (p<0.0001). Growth hormone levels were decreased in Tesamorelin-free group 2 and positive control in both NPHC and LPHC (p< 0.0001).

Conclusions The obesogenic activities of the LPHC diet exceeded that of the NPHC diet and interacted

with both integrase-containing and classical cART drug regimens to reproduce cART asso- ciated metabolic dysregulation. The effects were however reversed by co-administration

with tesamorelin, a synthetic growth hormone releasing hormone analogue.