Human Immunodeficiency Virus Persistence and T-Cell Activation in Blood, Rectal, and Lymph Node Tissue in Human Immunodeficiency Virus–Infected Individuals Receiving Suppressive Antiretroviral Therapy

<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background.</div>Immune activation and inflammation remain elevated in human immunodeficiency virus (HIV)–infected individuals receiving antiretroviral therapy (ART) and may contribute to HIV persistence.<div class="boxTitle">Methods.</div>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.<div class="boxTitle">Results.</div>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; <span style="font-style:italic;">P</span> < .001) and LN (2.32 fold-change in DNA; 95% CI = 1.22–4.41; <span style="font-style:italic;">P</span> = .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; <span style="font-style:italic;">P</span> = .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; <span style="font-style:italic;">P</span> = .02). Both associations were independent of current and nadir CD4⁺ T-cell counts.<div class="boxTitle">Conclusions.</div>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.</span>

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