Date Published: January 24, 2017
Publisher: Public Library of Science
Author(s): Catherine N. Le, Todd Hulgan, Chi-Hong Tseng, Ginger L. Milne, Jordan E. Lake, Alan Landay.
Arachidonic acid metabolites (eicosanoids) reflect oxidative stress and vascular health and have been associated with anthropometric measures and sex differences in cross-sectional analyses of HIV-infected (HIV+) persons. Telmisartan is an angiotensin receptor blocker and PPAR-γ agonist with potential anti-inflammatory and metabolic benefits. We assessed telmisartan’s effects on urine eicosanoids among HIV+ adults with central adiposity on suppressive antiretroviral therapy enrolled in a prospective clinical trial.
Thirty-five HIV+ adults (15 women; 20 men) completed 24 weeks of open-label oral telmisartan 40mg daily. Lumbar computed tomography quantified visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue. Urine F2-isoprostane (F2-IsoP), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB-M) were quantified at baseline and 24 weeks using gas/liquid chromatography-mass spectroscopy. Mann-Whitney-U tests compared sub-group differences; Spearman’s rho assessed correlations between clinical factors and eicosanoid levels.
Median PGE-M increased on telmisartan (p<0.01), with greater changes in men (+4.1 [p = 0.03] vs. +1.0 ng/mg cr in women; between-group p = 0.25) and participants losing >5% VAT (+3.7 ng/mg cr, p<0.01) and gaining >5% SAT (+1.7 ng/mg cr, p = 0.04). Median baseline F2-IsoP and TxB-M were slightly higher in women (both between-group p = 0.08) and did not change on telmisartan.
Urine PGE-M increased with 24 weeks of telmisartan in virally suppressed, HIV+ adults with central adiposity. Associations with favorable fat redistribution suggest increased PGE-M may reflect a beneficial response.
With advances in antiretroviral therapy (ART), the management of comorbid conditions in persons with well-controlled HIV has become increasingly important. We now recognize the intricate interplay between traditional risk factors, ART-associated metabolic disturbances, and the inflammatory milieu created by chronic HIV infection that leads to cardiovascular disease, disorders of glucose-insulin homeostasis, and adipose tissue dysfunction.[1–8] Traditional clinical tools used to risk-stratify these diseases in HIV-uninfected persons may underestimate risk in patients with well-controlled HIV, while biomarkers such as high-sensitivity C-reactive protein (hs-CRP) may be better surrogate markers for cardiovascular disease.[10,11]
This study prospectively assessed the effects of telmisartan therapy on urine eicosanoid measurements in treated HIV infection; to our knowledge the first to do so. In this group of HIV-infected adults with central adiposity on suppressive ART, 24 weeks of telmisartan resulted in a significant increase in PGE-M but not F2-IsoP, PGI-M, or TxB-M. Subgroup analysis revealed baseline differences by sex, with females having higher F2-IsoP and lower PGE-M. When adjusting for race in multivariate regression models, the relationship between F2-IsoP and sex remained robust while PGE-M was not associated with sex, with or without adjusting for race.
Urine PGE-M increased after 24 weeks of telmisartan therapy in HIV-infected adults on suppressive ART with central adiposity, with men and persons losing VAT and gaining SAT having the greatest increases. Associations with favorable adipose tissue redistribution suggest that increased PGE-M reflects a beneficial response. These pilot data suggest the utility of urine eicosanoids as potential biological mediators and/or biomarkers for inclusion in future studies in HIV-infected populations.