Effects of Telmisartan on Markers of Monocyte Activation in HIV+ Patients on ART
Jordan Lake*1, J Currier1, C-H Tseng1, D Douek2, and N Sandler2
1Univ of California, Los Angeles, US and 2NIAID, NIH, Bethesda, MD, US
Background: Soluble markers of monocyte activation CD14 and CD163 (sCD14 and sCD163) are elevated in inflammatory disorders and have been associated with fat mass in HIV– subjects and mortality and coronary plaque in HIV+ patients. Telmisartan (TEL), an angiotensin receptor blocker, improves visceral fat (VAT) volume and inflammation in HIV– subjects. In this single-arm, open-label, pilot study of standard-dose TEL on adipose tissue volumes in HIV+ patients with lipohypertrophy, we performed an exploratory analysis of changes in sCD14 and sCD163 during treatment with TEL.
Methods: HIV+ men and women with lipohypertrophy and HIV-1 RNA <48 copies/mL on ART received TEL 40 mg daily for 24 weeks. Adipose tissue volumes were quantified by L4-L5 single-slice CT at weeks 0 and 24. Plasma sCD14 and sCD163 levels were measured by ELISA. Categorical and continuous variables were compared using Fisher’s exact and Wilcoxon tests. Correlations were assessed using Spearman coefficients. For this exploratory analysis, statistical significance was set at a = 0.10.
Results: We enrolled 20 men and 15 women who completed the 24-week protocol. Characteristics at entry were: age 49, 77% non-white, 91% non-smokers, CD4 635 cells/mm3, and body mass index 34.6 kg/m2. Mean sCD163 decreased –219±853ng/mL at week 12 (p = 0.13), but rebounded to a net increase of 493±1870 ng/mL (p = 0.12) at week 24. Greater sCD163 increases occurred in women (861±1851 vs 218±883ng/mL in men, p = 0.093) and in subjects gaining VAT (1058±2033 vs 124±1743 ng/mL, p = 0.44). sCD163 increases correlated with less robust systolic (r = 0.36, p = 0.03) and diastolic (r = 0.32, p = 0.07) blood pressure responses to TEL. sCD14 increased 0.18±0.47x106 pg/mL over 24 weeks (p = 0.023) without gender- or fat-related differences. Changes in sCD14 correlated positively with changes in fasting glucose (r = 0.40, p = 0.01) and waist-to-hip ratio (r = 0.29, p = 0.10), and negatively with HDL cholesterol (r = –0.30, p = 0.06).
Conclusions: sCD14 and sCD163 increased over 24 weeks of TEL therapy, suggesting persistent monocyte activation in these HIV+ subjects well controlled on ART. Increases in sCD14 and sCD163 were associated with underlying metabolic dysregulation. Further studies are needed to understand the interplay between monocyte activation and metabolic disorders, and the HIV+ patient population(s) most likely to benefit from renin angiotensin system blockade.