Abstract
BackgroundIdentifying where human immunodeficiency virus (HIV) persists in people living with HIV and receiving antiretroviral therapy is critical to develop cure strategies. We assessed the relationship of HIV persistence to expression of chemokine receptors and their chemokines in blood (n = 48) and in rectal (n = 20) and lymph node (LN; n = 8) tissue collected from people living with HIV who were receiving suppressive antiretroviral therapy.MethodsCell-associated integrated HIV DNA, unspliced HIV RNA, and chemokine messenger RNA were quantified by quantitative polymerase chain reaction. Chemokine receptor expression on CD4+ T cells was determined using flow cytometry.ResultsIntegrated HIV DNA levels in CD4+ T cells, CCR6+CXCR3+ memory CD4+ T-cell frequency, and CCL20 expression (ligand for CCR6) were highest in rectal tissue, where HIV-infected CCR6+ T cells accounted for nearly all infected cells (median, 89.7%). Conversely in LN tissue, CCR6+ T cells were infrequent, and there was a statistically significant association of cell-associated HIV DNA and RNA with CCL19, CCL21, and CXCL13 chemokines.ConclusionsHIV-infected CCR6+ CD4+ T cells accounted for the majority of infected cells in rectal tissue. The different relationships between HIV persistence and T-cell subsets and chemokines in rectal and LN tissue suggest that different tissue-specific strategies may be required to eliminate HIV persistence and that assessment of biomarkers for HIV persistence may not be generalizable between blood and other tissues.
Highlights
Identifying where human immunodeficiency virus (HIV) persists in people living with HIV and receiving antiretroviral therapy is critical to develop cure strategies
The different relationships between HIV persistence and T-cell subsets and chemokines in rectal and lymph node (LN) tissue suggest that different tissue-specific strategies may be required to eliminate HIV persistence and that assessment of biomarkers for HIV persistence may not be generalizable between blood and other tissues
Human immunodeficiency virus (HIV) persists among people living with HIV (PLWH) and receiving suppressive antiretroviral therapy (ART) in resting and proliferating memory CD4+ T cells in blood and tissue [1,2,3,4]
Summary
Cell-associated integrated HIV DNA, unspliced HIV RNA, and chemokine messenger RNA were quantified by quantitative polymerase chain reaction. Chemokine receptor expression on CD4+ T cells was determined using flow cytometry. PLWH taking suppressive ART (HIV RNA, 350/μL were recruited at the University of California, San Francisco, and are described elsewhere [10, 28, 34]. The study was approved by the University of California, San Francisco Participant blood, LN, and rectal tissue samples were assessed for HIV DNA and RNA in sorted total CD4+ or CCR6+/CXCR3+ T-cell subsets, CKR immunophenotyping, or chemokine or transcription factor RNA (Supplementary Material). P values < .05 were considered statistically significant, and nominal P values were reported without adjustment for multiple comparisons, as outlined elsewhere [34] (Supplementary Material)
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