Chronic inflammation in HIV infection can lead to lymph node (LN) fibrosis and limit CD4+ T-cell recovery. Telmisartan, an angiotensin receptor blocker and PPAR-γ agonist, is anti-inflammatory and anti-fibrotic. We previously reported telmisartan did not decrease LN fibrosis (i.e. collagen I by immunohistochemistry (IHC)) more than ART alone. We hypothesized telmisartan would decrease macrophage infiltration and HIV-1 RNA+ cells and increase CD4+ T-cells in LN.
In this completed, randomized-controlled trial, adults with HIV-1 RNA <50 copies/mL on ART for ≥48 weeks received telmisartan plus ART for 48 weeks or ART alone. The number of LN HIV-1 RNA+ (vRNA+) cells was measured by RNAscope and % CD4+ T cells and CD68+CD163+ macrophages by IHC at weeks 0 and 48. Statistical testing used two-sided rank-sum, signed-rank tests and Spearman correlations (α=0.05).
Of 44 participants, 93% were male, 50% white non-Hispanic, median age 48 years, CD4+ T-cell count 588 cells/mm…3…. Week 0 median (IQR) number of vRNA+ cells/10…6… cells was 106 (67, 130; n=17) in the telmisartan arm and 75 (0, 118; n=13) for ART alone. By morphology, vRNA+ cells were lymphocytes. After 48 weeks, the number of vRNA+ cells/10…6… cells changed by -48 (-88, 0; P=0.004) in the telmisartan arm and +18 (-91, 45; P=0.70) with ART alone, with P=0.28 for the between-arm comparison. Median abundance of CD4+ T cells and macrophages in the B cell follicle (BCF) and T cell zone (TCZ) did not change significantly in either arm. With pooled treatment arms at Week 0, having less LN collagen I was associated with more CD4+ T cells in TCZ (r=-0.47, P=0.004). Having more vRNA+ cells was associated with fewer CD4+ T cells in BCF (r=-0.40, P=0.03) and fewer macrophages in BCF (r=-0.38, P=0.04) and TCZ (r=-0.35, P=0.04). While not associated at Week 0, 48-week increases in CD4+ T cells in TCZ were associated with decreases in macrophages in BCF (r=-0.60, P=0.0009) and TCZ (r=-0.60, P=0.0005) in a pooled analysis.
The number of LN HIV-1 RNA+ cells declined 45% with telmisartan added to suppressive ART. At Week 0, people with less LN fibrosis and fewer vRNA+ cells had more LN CD4+ T cells. Decreases in macrophages were accompanied by better LN CD4+ T cell recovery. Further characterization of these macrophages and the reservoir will clarify the interactions between HIV-1, LN immune cells, and their effects on fibrosis and the HIV reservoir.