Immune correlates of cardiovascular co-morbidity in HIV infected participants from South India.

BACKGROUND: Understanding the immune correlates of cardiovascular disease (CVD) risk in HIV infection is an important area of investigation in the current era of aging with HIV infection. Less is known about CVD risk and HIV infection in developing nations where additional risk factors may be playing a role in the CVD development. In this study, we assessed the effects of systemic inflammation, microbial translocation (MT), T cell immune activation (IA), and nadir CD4 counts on cardiac function and arterial stiffness as markers of subclinical atherosclerosis in HIV-infected individuals. METHODS: People with HIV (PWH) who were ART naïve (n = 102) or virally suppressed on ART (n = 172) were stratified on nadir CD4 counts and compared to HIV-uninfected controls (n = 64). Determination was made of cardiac function via radial pulse wave and carotid intima thickness (C-IMT) measurements. Plasma biomarkers of inflammation and MT by ELISA or multiplex assays, and immune activation (IA) of T cells based HLA-DR and CD38 expression were investigated by flow cytometry. T-test, Mann-Whitney U test, and Spearman correlation were used to analyze study parameters. RESULTS: Reduction in cardiac function with lower cardiac ejection time (p < 0.001), stroke volume (p < 0.001), cardiac output (p = 0.007), higher arterial stiffness (p < 0.05) were identified in ART-naïve participants, compared to PWH on ART (p < 0.05). No significant difference in C-IMT values were noted. Higher inflammatory and MT markers were found in the ART-naïve group compared to treated group who were comparable to uninfected participants, except for having higher TNF-α (p < 0.001) and sCD14 (p < 0.001). Immune activation of CD4 and CD8 T-cells was greater in ART-naïve participants compared to ART-treated and uninfected controls (p < 0.05). Lower nadir CD4 counts, higher inflammation, and higher MT predicted poor cardiac measures in the ART-naïve with nadir CD4 < 200cells/mm3 manifesting the highest arterial stiffness, and lowest cardiac function, whereas ART-treated, even with nadir < 200 cells/mm3 were similar to uninfected in these measures. CONCLUSIONS: In HIV-infected individuals, initiation of ART even at nadir of < 200 cells/mm3 may prevent or reverse cardiovascular disease outcomes that are easily measurable in low income countries.

Impact of Early Antiretroviral Therapy Initiation on HIV-Specific CD4 and CD8 T Cell Function in Perinatally Infected Children.

Early initiation of antiretroviral therapy (ART) in vertically HIV-infected children limits the size of the virus reservoir, but whether the time of treatment initiation (TI) can durably impact host immune responses associated with HIV infection is still unknown. This study was conducted in PBMC of 20 HIV-infected virally suppressed children on ART (mean age 9.4 y), classified as early treated (ET; age at ART initiation ≤0.5 y, n = 14) or late treated (LT; age at ART initiation 1-10 y, n = 6). Frequencies and functions of Ag-specific CD4 (CD40L+) and CD8 (CD69+) T cells were evaluated by intracellular IL-2, IFN-γ, and TNF-α production with IL-21 in CD4 or CD107a, granzyme B and perforin in CD8 T cells following stimulation with HIV gp140 protein (ENV) or GAG peptides by multiparameter flow cytometry. ET showed a higher proportion of cytokine-producing ENV- and GAG-specific CD4 and CD8 T cells compared with LT. In particular, ET were enriched in polyfunctional T cells. RNA sequencing analysis showed upregulation of immune activation pathways in LT compared with ET. Our results suggest that timing of TI in HIV-infected children has a long-term and measurable impact on the quality of the HIV-specific T cell immune responses and transcriptional profiles of PBMC, reinforcing the importance of early TI.