Tesamorelin mitigates cART-induced metabolic syndrome and preserves growth hormone in rats on obesogenic diets

Combined antiretroviral therapy (cART) has transformed HIV treatment, but it's increasingly linked to metabolic syndrome, including dyslipidemia, insulin resistance, and increased adiposity. This significantly raises the risk of cardiovascular disease in people living with HIV. Poor nutritional status at cART initiation is a known predictor of mortality, independent of immune status. Current cART regimens, particularly integrase inhibitor-containing regimens (INI-CR), can exacerbate these metabolic issues, highlighting a critical need for adjunctive therapies that can counteract these adverse effects and improve long-term patient outcomes.

Researchers investigated the interplay of dietary regimens and cART on metabolic syndrome development in 120 freshly weaned Sprague Dawley rats. Animals were initially randomized into standard, low protein high calorie (LPHC), and normal protein high calorie (NPHC) diet groups (n = 40/group) for 15 weeks. Subsequently, each diet group was subdivided into four treatment arms (n = 10/group) for 9 weeks: Control (normal saline), Group 1 (TDF+3TC+DTG + Tesamorelin), Group 2 (TDF+3TC+DTG), and Positive Control (AZT+3TC+ATV/r). Primary endpoints included weekly body weights, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), lipid profiles, liver weights, hepatic triglycerides, and adiposity, all assessed at week 24.

At week 15, significant body weight increases were observed across diet groups (standard: 146 ± 1.64g to 273.1 ± 1.56g; NPHC: 143.5 ± 2.40g to 390.2 ± 4.94g; LPHC: 145.5 ± 2.28g to 398.3 ± 4.89g), all with p<0.0001. Similar increases were noted in FBG and OGTT (p<0.0001). In the subsequent 9-week treatment phase, the cART-only Group 2 and the Positive Control group, across both NPHC and LPHC diets, showed significant increases in FBG, OGTT, body weights, lipid profiles, liver weights, hepatic triglycerides, adiposity, and insulin levels (p<0.0001 for all). This indicates a strong obesogenic and diabetogenic effect of cART combined with high-calorie diets. Importantly, growth hormone levels were significantly decreased in the Tesamorelin-free Group 2 and Positive Control groups under both NPHC and LPHC diets (p<0.0001). The obesogenic activities of the low protein high calorie (LPHC) diet exceeded that of the normal protein high calorie (NPHC) diet, and these effects interacted synergistically with both integrase inhibitor-containing and protease inhibitor-containing cART regimens.