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Losartan Does Not Improve Inflammation or Fibrosis Markers in Older People on ART
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CROI 2020, March 8-11, 2020, Boston
Mark Mascolini
Losartan, an antihypertensive angiotensin receptor blocker, did not improve markers of inflammation, fibrosis, or T-cell recovery in older antiretroviral-treated adults enrolled in a placebo-controlled trial [1]. Losartan's failure as an antiinflammatory or antifibrotic underscores the difficulty in addressing these HIV-related complications with medication.
Researchers from the University of Minnesota and other US centers hypothesized that losartan may curb the risk of diseases associated with inflammation and lymph node fibrosis, besides lowering blood pressure. The LIFE HIV Study recruited 108 people 50 and older with antiretroviral-induced HIV control and a CD4 count below 600. Researchers randomized 52 to 100 mg of losartan daily and 56 to placebo. The primary study outcome was change in the inflammation marker IL-6.
Fifty of 52 people randomized to losartan and 55 of 56 randomized to placebo completed the 12-month trial. The group had a median age of 56 (interquartile range [IQR] 53 to 61), 96% were men, and 56% were white. A median body mass index of 26.8 kg/m2 put the group in the overweight range, but only 20% currently smoked, 22% had hypertension, and 26% took lipid-lowering drugs. Median nadir CD4 count stood at a low 120, and a stunted CD4/CD8 ratio 0.57 confirmed the perilous immunologic history of this group. Current median CD4 count stood at 408 (IQR 310 to 498). Half of these people were taking an integrase inhibitor. At study entry median IL-6 measured 1.1 pg/mL (IQR 0.70 to 1.39).
Compared with placebo, 1 year of daily losartan had little impact on IL-6 (effect estimate 0.6%, 95% confidence interval [CI] -14.7% to 18.7%). Nor did losartan significantly affect other inflammation markers (TNF R1, sCD163, sCD14, neopterin), the coagulation marker D-dimer, or the fibrosis markers hyaluronic acid or beta-crosslaps. These analyses controlled for baseline biomarker levels. Losartan did have a greater impact in lowering IL-6 in the one third of participants over 60 years old, but this effect fell short of statistical significance.
Changes in CD4 count, CD8 count, and CD4/CD8 ratio did not differ significantly between the losartan and placebo groups. Nor did losartan improve levels of any T-cell memory subset, lymph node CD4 count, or lymph node collagen.
Compared with placebo, losartan did significantly improve systolic blood pressure, diastolic blood pressure, and the kidney function signal estimated glomerular filtration rate (eGFR).
The LIFE-HIV team concluded that "losartan treatment given in addition to antiretroviral therapy is unlikely to reduce inflammation and associated co-morbidities, beyond the benefits from lowering blood pressure."
Reference
1. Baker JV, Wolfson J, Collins G, et al. Losartan to reduce inflammation and fibrosis endpoints in HIV disease (LIFE-HIV). Conference on Retroviruses and Opportunistic Infections (CROI). March 8-11, 2020. Boston. Abstract 84.
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