Chronic HIV infection is characterized by persistent inflammation and immune activation that can lead to tissue injury and fibrosis. Lymph node (LN) fibrosis may limit CD4+ T-cell recovery; LN and adipose tissue (AT) fibrosis may contribute to systemic inflammation and comorbidities. Telmisartan is an angiotensin receptor blocker and PPAR-γ agonist with anti-inflammatory and anti-fibrotic properties. We hypothesized that telmisartan would decrease LN or AT fibrosis in HIV-1 infected adults on suppressive antiretroviral therapy (ART).
In this completed, randomized-controlled trial, HIV-infected participants age ≥18 years with HIV-1 RNA <50 copies/mL on ART for ≥48 weeks received telmisartan 40mg daily for 4 weeks then 80mg daily for 44 weeks or no drug while continuing ART. Primary endpoints were changes in % collagen I deposition by immunohistochemistry (IHC) in inguinal LN and subcutaneous lower abdominal AT after 48 weeks. IHC was performed and interpreted by a blinded central reader. 36 participants would power the study to detect a 4% difference in change in collagen. Statistical testing used two-sided rank-sum and signed-rank tests (α=0.05).
Of 44 randomized participants, 93% were male and 50% white non-Hispanic. Median age was 48 years, body mass index 25 kg/m², and CD4+ T-cell count 588 cells/mm³. Paired AT samples were available from 34 participants and LN from 29 due to participant consent and sample quality. Baseline median (interquartile range) tissue area with collagen I deposition was 13.7% (7.5%, 21.4%) for LN and 1.9% (0.4%, 3.4%) for AT. No statistically significant between-group differences in LN or AT collagen I deposition change were observed (Table), although a larger than expected variability in LN collagen likely reduced power to see a significant LN effect. In both arms, collagen I deposition tended to decrease in LN and significantly decreased in AT over 48 weeks.
In HIV-1-infected adults on suppressive ART, angiotensin receptor blockade and PPAR-γ agonism with telmisartan for 48 weeks did not improve LN or AT fibrosis more than continued ART alone. Notably, continued ART decreased both LN and AT fibrosis over 48 weeks. This trial is the first longitudinal study of LN and AT fibrosis in treated HIV infection and will inform design of future studies with tissue endpoints. Analyses of tissue HIV expression and circulating and tissue-level inflammatory and fibrotic signatures are ongoing.