title: A correlate of HIV-1 control consisting of both innate and adaptive immune parameters best predicts viral load by multivariable analysis in HIV-1 infected viremic controllers and chronically-infected non-controllers.
abstract: HIV-1 infected viremic controllers maintain durable viral suppression below 2000 copies viral RNA/ml without anti-retroviral therapy (ART), and the immunological factor(s) associated with host control in presence of low but detectable viral replication are of considerable interest. Here, we utilized a multivariable analysis to identify which innate and adaptive immune parameters best correlated with viral control utilizing a cohort of viremic controllers (median 704 viral RNA/ml) and non-controllers (median 21,932 viral RNA/ml) that were matched for similar CD4+ T cell counts in the absence of ART. We observed that HIV-1 Gag-specific CD8+ T cell responses were preferentially targeted over Pol-specific responses in viremic controllers (p = 0.0137), while Pol-specific responses were positively associated with viral load (rho = 0.7753, p = 0.0001, n = 23). Viremic controllers exhibited significantly higher NK and plasmacytoid dendritic cells (pDC) frequency as well as retained expression of the NK CD16 receptor and strong target cell-induced NK cell IFN-gamma production compared to non-controllers (p<0.05). Despite differences in innate and adaptive immune function however, both viremic controllers (p<0.05) and non-controller subjects (p<0.001) exhibited significantly increased CD8+ T cell activation and spontaneous NK cell degranulation compared to uninfected donors. Overall, we identified that a combination of innate (pDC frequency) and adaptive (Pol-specific CD8+ T cell responses) immune parameters best predicted viral load (R2 = 0.5864, p = 0.0021, n = 17) by a multivariable analysis. Together, this data indicates that preferential Gag-specific over Pol-specific CD8+ T cell responses along with a retention of functional innate subsets best predict host control over viral replication in HIV-1 infected viremic controllers compared to chronically-infected non-controllers.
authors: The Wistar Institute, HIV Immunopathogenesis Laboratory, Philadelphia, Pennsylvania, United States of America.
authors: Costin
authors: C
authors: Tomescu
authors: The Wistar Institute, Biostatistics Laboratory, Philadelphia, Pennsylvania, United States of America.
authors: Qin
authors: Q
authors: Liu
authors: The Wistar Institute, HIV Immunopathogenesis Laboratory, Philadelphia, Pennsylvania, United States of America.
authors: Brian N
authors: BN
authors: Ross
authors: The Wistar Institute, Biostatistics Laboratory, Philadelphia, Pennsylvania, United States of America.
authors: Xiangfan
authors: X
authors: Yin
authors: UPENN-Presbyterian Medical Center, Philadelphia, Pennsylvania, United States of America.
authors: Kenneth
authors: K
authors: Lynn
authors: Philadelphia FIGHT, The Jonathan Lax Treatment Center, Philadelphia, Pennsylvania, United States of America.
authors: Karam C
authors: KC
authors: Mounzer
authors: UPENN-Presbyterian Medical Center, Philadelphia, Pennsylvania, United States of America.
authors: Jay R
authors: JR
authors: Kostman
authors: The Wistar Institute, HIV Immunopathogenesis Laboratory, Philadelphia, Pennsylvania, United States of America.
authors: Luis J
authors: LJ
authors: Montaner
mesh_terms: D056704:Adaptive Immunity; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007113:Immunity, Innate; D015999:Multivariate Analysis; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014766:Viremia
chemical_list: D012367:RNA, Viral