Immune activation and inflammation remain elevated in human immunodeficiency virus (HIV)–infected individuals receiving antiretroviral therapy (ART) and may contribute to HIV persistence.

Using flow cytometry expression of CD38, HLA-DR and PD-1 were measured in blood (n = 48), lymph node (LN; n = 9), and rectal tissue (n = 17) from virally suppressed individuals. Total and integrated HIV DNA, 2-LTR circles, and cell-associated unspliced HIV RNA were quantified.

CD4⁺ T cells from rectal tissue had a higher frequency of integrated HIV DNA compared with blood (4.26 fold-change in DNA; 95% confidence interval [CI] = 2.61–7.00; P < .001) and LN (2.32 fold-change in DNA; 95% CI = 1.22–4.41; P = .01). In rectal tissue, there were positive associations between integrated HIV DNA with PD-1⁺ CD4⁺ T-cells (1.44 fold-change in integrated HIV DNA per 10-unit increase in PD-1⁺ CD4⁺ T cells; 95% CI = 1.01–2.05; P = .045) and CD38⁺HLA-DR⁺ CD8⁺ T cells (1.40 fold-change in integrated HIV DNA per 1-unit increase in CD38⁺HLA-DR⁺ CD8⁺ T cells; 95% CI = 1.05–1.86; P = .02). Both associations were independent of current and nadir CD4⁺ T-cell counts.

During ART, rectal tissue is an important reservoir for HIV persistence with a high frequency of activated CD4⁺ and CD8⁺ T cells. PD-1 may represent a marker of HIV persistence in rectal tissue.