Article ; Online: T cells with high PD-1 expression are associated with lower HIV-specific immune responses despite long-term antiretroviral therapy.
2020 Volume 34, Issue 1, Page(s) 15–24
Abstract: Objective: We evaluated frequencies of T cells with high PD-1 expression (PD-1) before and after long-term effective antiretroviral therapy (ART), and determined if frequencies on-ART correlated positively with measures of HIV persistence and negatively ...
| Abstract | Objective: We evaluated frequencies of T cells with high PD-1 expression (PD-1) before and after long-term effective antiretroviral therapy (ART), and determined if frequencies on-ART correlated positively with measures of HIV persistence and negatively with HIV-specific responses. Methods: We enrolled individuals who started ART during chronic infection and had durable suppression of viremia for at least 4 years (N = 99). We assessed PD-1 T-cell frequencies at timepoints pre-ART and on-ART using flow cytometry, and evaluated how frequencies on-ART are associated with measures of HIV persistence, HIV-specific immune responses, and immune activation levels. Results: Pre-ART, PD-1 CD4 T cells correlated positively with viremia and negatively with CD4 T-cell count. At year 1 on-ART, %PD-1 CD4 T cells decreased but then remained stable at 4 and 6-15 years on-ART, whereas %PD-1 CD8 T cells on-ART remained similar to pre-ART. PD-1 CD4 T cells correlated positively with HIV DNA pre-ART and on-ART, and with CD4 T-cell activation on-ART. PD-1 CD4 T cells negatively correlated with HIV Gag-specific and Env-specific T-cell responses but not with CMV-specific or EBV-specific responses. PD-1 CD8 T cells trended towards a negative correlation with responses to Gag and Env, but not to CMV and EBV. Conclusion: PD-1 T cells persist in blood despite prolonged suppression on ART, correlate with HIV DNA levels, and are associated with lower HIV-specific T-cell responses but not CMV-specific or EBV-specific responses, suggesting that these cells are HIV-specific. The findings support evaluating PD-1 blockade strategies for their effect on HIV persistence and HIV-specific immunity. |
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| MeSH term(s) | Adult ; Anti-HIV Agents/therapeutic use ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Female ; HIV Infections/drug therapy ; HIV Infections/immunology ; Humans ; Lymphocyte Activation ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor/metabolism ; Viral Load ; gag Gene Products, Human Immunodeficiency Virus/immunology |
| Chemical Substances | Anti-HIV Agents ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; gag Gene Products, Human Immunodeficiency Virus |
| Language | English |
| Publishing date | 2020-02-12 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 639076-6 |
| ISSN | 1473-5571 ; 0269-9370 ; 1350-2840 |
| ISSN (online) | 1473-5571 |
| ISSN | 0269-9370 ; 1350-2840 |
| DOI | 10.1097/QAD.0000000000002406 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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