Losartan to reduce inflammation and fibrosis endpoints in HIV disease (LIFE-HIV): results from a randomized placebo-controlled trial.

Background Persistent inflammation and incomplete immune recovery among persons with HIV are associated with increased disease risk. We hypothesized that the angiotensin receptor blocker (ARB) losartan would reduce inflammation by mitigating NFκB responses and promote T-cell recovery via inhibition of TGFβ mediated fibrosis. Methods Losartan (100 mg) versus placebo over 12 months was investigated in a randomized (1:1) placebo-controlled trial, among persons with HIV (PHIV) age ≥50 years, receiving ART, with HIV RNA Results Among 108 PHIV (n = 52 to losartan; n = 56 to placebo), 97% had a month 12 visit. Median age was 57 years and baseline CD4+ count was 408 cells/mm. Losartan treatment was not associated with an improvement in IL-6 levels, or other blood measures of inflammation, immune activation, fibrosis activity, or myocardial function. CD4+ and CD8+ T-cells also did not differ by treatment group. Losartan reduced systolic and diastolic blood pressure by 6 and 5mmHg, respectively. Conclusions Among older PHIV with viral suppression, losartan did not improve blood measures of inflammation nor T-cell immune recovery. Losartan treatment is unlikely to reduce inflammation associated co-morbidities to a clinically meaningful degree, beyond the benefits from lowering blood pressure. CLINICALTRIALS.GOV:: NCT02049307.