Losartan to reduce inflammation and fibrosis endpoints in HIV disease.
AIDS
; 35(4): 575-583, 2021 03 15.
Article
em En
| MEDLINE
| ID: mdl-33252490
ABSTRACT
BACKGROUND:
Persistent inflammation and incomplete immune recovery among persons with HIV (PHIV) are associated with increased disease risk. We hypothesized that the angiotensin receptor blocker (ARB) losartan would reduce inflammation by mitigating nuclear factor (NF)κB responses and promote T-cell recovery via inhibition of transforming growth factor-beta (TGFß)-mediated fibrosis.METHODS:
Losartan (100âmg) versus placebo over 12 months was investigated in a randomized (1ââ1) placebo-controlled trial, among PHIV age at least 50 years, receiving antiretroviral therapy (ART), with HIV RNA less than 200âcopies/ml and CD4+ cell count 600âcells/µl or less. Inflammation, fibrosis and myocardial biomarkers were measured in blood using ELISA, electrochemiluminescence and immunoturbidimetric methods, and T-cell and monocyte phenotypes were assessed with flow cytometry among a subset of participants. Changes over follow-up in (log-2 transformed) biomarkers and cell phenotypes (untransformed) were compared between losartan and placebo arms using linear mixed models.RESULTS:
Among 108 PHIV (nâ=â52 to losartan; nâ=â56 to placebo), 97% had a month 12 visit. Median age was 57 years and baseline CD4+ cell count was 408âcells/µl. Losartan treatment was not associated with an improvement in interleukin-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 SBP and DBP by 6 and 5âmmHg, respectively.CONCLUSION:
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 comorbidities to a clinically meaningful degree, beyond the benefits from lowering blood pressure. CLINICALTRIALSGOV NCT02049307.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Losartan
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article