Abstract
BackgroundVisceral adiposity in the setting of HIV infection and antiretroviral therapy (ART) is not fully understood, and treatment options remain limited. Telmisartan, an angiotensin receptor blocker and partial PPAR-γ agonist, has been shown to decrease visceral fat and improve metabolic and inflammatory parameters in HIV-uninfected subjects.MethodsHIV-infected subjects with HIV-1 RNA <50 copies/mL on ART and (women/men) waist circumference >94/95 cm or waist: hip ratio >0.88/0.94 received open-label telmisartan 40 mg po daily for 24 weeks. Adipose tissue (AT) volumes were quantified by L4–L5 single slice computed tomography. Metabolic and inflammatory markers were obtained fasting. Thirty-five subjects provided 80% power to detect a 10% 24-week decrease in visceral AT (VAT, two-sided α = 0.05).ResultsThirty-five subjects enrolled and completed the protocol. At entry (median or %): age 49 years, 43% female, 77% non-white, 91% non-smokers, CD4+ T cell count 590 cells/mm3, BMI 31 kg/m2. AT responses were heterogeneous, with statistically significant losses of median (IQR) total (TAT, 2.9% (−9.8, 0.7), p = 0.03) and subcutaneous (SAT, −2.7% (−9.8, 1.1), p = 0.03) AT, but not VAT (−2.7% (−20.5, 14.2), p = 0.53). Significant decreases in waist circumference and waist:hip ratio occurred (both p<0.001) without BMI or weight changes. In an exploratory analysis, significant increases in TNF-α occurred among female subjects without changes in other inflammatory or metabolic markers. No related adverse events occurred.ConclusionsTelmisartan was well tolerated. Small losses of AT from all depots were observed after 24 weeks of telmisartan therapy. Further study is needed to determine whether HIV-infected patients can receive metabolic benefits from telmisartan.Trial RegistrationClinicalTrials.gov NCT01088295
Highlights
In the setting of HIV infection, lipohypertrophy is characterized by truncal subcutaneous (SAT) and visceral (VAT) fat accumulation that is often associated with metabolic abnormalities such as hyperlipidemia, insulin resistance, and increased cardiovascular risk [1,2,3,4,5]
Sixteen subjects were unable to have their Weeks 0 and 24 computed tomography (CT) scans performed on the same scanner; phantom scan comparison revealed no significant scanner discrepancies requiring calculation of a correction factor, and sensitivity analysis revealed Adipose tissue (AT) volumes were precise to 61 cm2
No subject reported a change from baseline in initiation or dosing of lipid- (n = 19) or glucose-lowering agents (n = 5) or androgen supplementation (n = 6) during the 24-week study period
Summary
In the setting of HIV infection, lipohypertrophy is characterized by truncal subcutaneous (SAT) and visceral (VAT) fat accumulation that is often associated with metabolic abnormalities such as hyperlipidemia, insulin resistance, and increased cardiovascular risk [1,2,3,4,5]. Metformin, which improves insulin sensitivity in patients with diabetes and polycystic ovarian syndrome, has been shown in HIV infection to improve VAT accumulation but exacerbate peripheral lipoatrophy, [6,7] which may be an independent risk factor for cardiovascular disease. Both HIV and antiretroviral therapy (ART, the protease inhibitor and nucleoside reverse transcriptase inhibitor classes of agents) may modulate lipodystrophy via down-regulation of partial peroxisome proliferatoractivated receptor-gamma (PPAR-c) [8,9]. Telmisartan, an angiotensin receptor blocker and partial PPAR-c agonist, has been shown to decrease visceral fat and improve metabolic and inflammatory parameters in HIV-uninfected subjects
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