Telmisartan did not affect biomarkers of central nervous system (CNS) inflammation or injury when used as an adjunct to antiretroviral therapy (ART) for acute HIV infection, but a possible trend was detected, according to a poster presented at the virtual Conference on Retroviruses and Opportunistic Infections, held March 8 to 11, 2020.
The effects of HIV infection on the CNS may be established early in the course of infection and thus intervention during the acute phase of HIV infection. Telmisartan is an angiotensin II receptor antagonist that inhibits inflammatory cytokines and macrophage activity. The researchers evaluated the hypothesis that initiation of ART with adjunctive telmisartan in acute HIV could potentially decrease immune activation and inflammation and amend CNS HIV pathogenesis.
In this pilot study, 21 participants were randomly assigned in a 2:1 ratio to receive either the intervention with telmisartan or no intervention for 48 weeks, and thereafter all individuals received only ART treatment until the study endpoint at 72 weeks. Neuropsychologic testing was performed using a summarization of 16 distinct tests.
Furthermore, samples of blood and cerebrospinal fluid (CSF), biomarkers of HIV infection, inflammation, and neuronal injury, as well as spectroscopy and magnetic resonance imaging of the brain were collected to investigate brain function and inflammation. Nonparametric tests were used for statistical analyses.
The analysis of all neuropsycholigic tests revealed that the patients in the telmisartan treatment group demonstrated significant improvement between week 0 and 48 (P =.013) and week 0 and 72 (P =.04). In comparison, the control group demonstrated no change during the same period. Univariate analysis of variance of the data showed consistency with this trend, however it was not able to detect a difference due to the study being underpowered. Treatment with telmisartan did not reveal any significant impacts on neurological inflammation or injury measured by CSF markers or modified Rankin Scale.
A limitation of the study is the small sample size, leading to several analyses being underpowered. The study authors stressed that further work is needed to clarify the association with improved neuropsychological testing performance.
Peluso MJ, Kroon E, Chan P, Tipsuk S, Sacdalan C, Belden A, et al. A randomized trial of adjunctive telmisartan to reduce CNS inflammation in acute HIV. Poster presented at: CROI 2020. March 8-11, 2020. http://www.croiconference.org/sites/default/files/uploads/croi2020-boston-abstract-ebook.pdf. Accessed March 18, 2020.