The CD38+ HLA-DR+ PD-1+ CD4 T cell population represents a short-lived part of the viral reservoir and predicts poor immunologic recovery upon initiation of ART

• Published in: The Journal of immunology (1950) Vol. 198; no. 1_Supplement; pp. 78 - 78.28
• Main Authors: Eller, Michael A., Creegan, Matthew, Hong, Ting, Nau, Marty, Slike, Bonnie M., Krebs, Shelly J., McElrath, M. Juliana, Katabira, Elly T, Michael, Nelson L., Robb, Merlin L., Tovanabutra, Sodsai, Baeten, Jared M., Sandberg, Johan K.
• Format: Journal Article
• Language: English
• Published: 01.05.2017
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.198.Supp.78.28

Abstract The activated PD-1+ CD4 T cell population is associated with disease progression in untreated HIV-1 infection, and with residual viral replication in individuals on ART. Few studies have examined cell associated viral load (CAVL) in phenotypically different activated CD4 T cell populations to define the HIV reservoir. We followed 32 HIV-1 chronically infected individuals, from Kampala, Uganda, and determined their CD4 T cell counts, and viral load at baseline, 6, and 12 months after the initiation of ART. Peripheral blood T cell populations were sorted based on activation profiles and gag DNA was measured to determine CAVL within these populations. Soluble inflammatory factors were measured in plasma using a multiplexed platform. The median HIV-1 viral load declined from 95,315 copies/ml at baseline to below detection for all patients after 12 months of ART, whereas CD4 T cells counts averaged 204 cells/μl at baseline and increased to 373 cells/μl by month 12. Median levels of the activated PD-1+ CD4 T cell population contracted from 4.5% of CD4 T cells at baseline to 2.3% of CD4 T cells after 12 months of ART. Baseline levels of activated PD-1+ CD4 T cells positively correlated with plasma levels of IP-10 (R2=0.362, P<0.001) and TNFRII (R2=0.237, P=0.006). Higher baseline level of activated PD-1 positive CD4 T cells was associated with poorer CD4 T cell recovery after 12 months of ART (R2=0.240, P=0.039). CAVL was similar within the activated PD-1+ CD4 T cell population as other CD4 populations at baseline, but significantly lower after 12 months of ART compared to baseline. Taken together, the activated PD-1+ CD4 T cell population is a short-lived component of the viral reservoir and high levels of these cells predict poor immunologic recovery on ART.