10 [50] H. He, P. N. Nehete, B. Nehete et al., “Functional impairment of central memory CD4 T cells is a potential early prognostic marker for changing viral load in SHIV-infected rhesus macaques,” PLoS ONE, vol. 6, no. 5, Article ID e19607, 2011. [51] M. Goicoechea, D. Smith, S. May, C. Mathews, and C. Spina, “Prevalence and T-cell phenotype of slow HIV disease progressors with robust HIV replication,” Journal of Acquired Immune Deﬁciency Syndromes, vol. 52, no. 2, pp. 299–301, 2009. [52] S. Resino, R. Correa, J. M. Bellon, and M. A. Munoz- Fernandez, “Preserved immune system in long-term asymp- tomatic vertically HIV-1 infected children,” Clinical & Exper- imental Immunology, vol. 132, no. 1, pp. 105–112, 2003. [53] G. Khoury, R. Rajasuriar, P. U. Cameron, and S. R. Lewin, “The role of naive T-cells in HIV-1 pathogenesis: an emerging key playerc,” Clinical Immunology, vol. 141, no. 3, pp. 253– 267, 2011. [54] S. Kimmig, G. K. Przybylski, C. A. Schmidt et al., “Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood,” Journal of Experimental Medicine, vol. 195, no. 6, pp. 789– 794, 2002. [55] S. Junge, B. Kloeckener-Gruissem, R. Zuﬀerey et al., “Cor- relation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children,” European Journal of Immunol- ogy, vol. 37, no. 11, pp. 3270–3280, 2007. [56] F. N. Engsig, J. Gerstoft, G. Kronborg et al., “Long-term mortality in hiv patients virally suppressed for more than three years with incomplete CD4 recovery: a cohort study,” BMC Infectious Diseases, vol. 10, article 318, 2010. [57] L. S. Park, D. J. Friend, A. E. Schmierer, S. K. Dower, and A. E. Namen, “Murine interleukin 7 (IL-7) receptor. Char- acterization on an IL-7-dependent cell line,” Journal of Experimental Medicine, vol. 171, no. 4, pp. 1073–1089, 1990. [58] A. Llano, J. Barretina, A. Gutie´rrez et al., “Interleukin-7 in plasma correlates with CD4 T-cell depletion and may be associated with emergence of syncytium-inducing variants in human immunodeﬁciency virus type 1-positive individuals,” Journal of Virology, vol. 75, no. 21, pp. 10319–10325, 2001. [59] B. Rethi, C. Fluur, A. Atlas et al., “Loss of IL-7Rα is associated with CD4 T-cell depletion, high interleukin-7 levels and CD28 down-regulation in HIV infected patients,” AIDS, vol. 19, no. 18, pp. 2077–2086, 2005. [60] C. Fluur, B. Rethi, P. H. Thang et al., “Relationship between serum IL-7 concentrations and lymphopenia upon diﬀerent levels of HIV immune control,” AIDS, vol. 21, no. 8, pp. 1048–1050, 2007. [61] J. V. Giorgi, L. E. Hultin, J. A. McKeating et al., “Shorter survival in advanced human immunodeﬁciency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage,” Journal of Infectious Diseases, vol. 179, no. 4, pp. 859–870, 1999. [62] A. E. Sousa, J. Carneiro, M. Meier-Schellersheim, Z. Gross- man, and R. M. M. Victorino, “CD4 T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2 but only indirectly to the viral load,” Journal of Immunology, vol. 169, no. 6, pp. 3400–3406, 2002. [63] Z. Grossman, M. Meier-Schellersheim, A. E. Sousa, R. M. M. Victorino, and W. E. Paul, “CD4+ T-cell depletion in HIV infection: are we closer to understanding the cause?” Nature Medicine, vol. 8, no. 4, pp. 319–323, 2002. AIDS Research and Treatment [64] M. D. Hazenberg, S. A. Otto, B. H. B. Van Benthem et al., “Persistent immune activation in HIV-1 infection is associ- ated with progression to AIDS,” AIDS, vol. 17, no. 13, pp. 1881–1888, 2003. [65] Z. Liu, W. G. Cumberland, L. E. Hultin, A. H. Kaplan, R. Detels, and J. V. Giorgi, “CD8+ T-lymphocyte activation in HIV-1 disease reﬂects an aspect of pathogenesis distinct from viral burden and immunodeﬁciency,” Journal of Acquired Immune Deﬁciency Syndromes & Human Retrovirology, vol. 18, no. 4, pp. 332–340, 1998. [66] Z. Liu, W. G. Cumberland, L. E. Hultin, H. E. Prince, R. Detels, and J. V. Giorgi, “Elevated CD38 antigen expression on CD8+ T cells is a stronger marker for the risk of chronic HIV disease progression to AIDS and death in the Multi- center AIDS Cohort Study than CD4+ cell count, soluble immune activation markers, or combinations of HLA-DR and CD38 expression,” Journal of Acquired Immune Deﬁ- ciency Syndromes & Human Retrovirology, vol. 16, no. 2, pp. 83–92, 1997. [67] Z. Liu, L. E. Hultin, W. G. Cumberland et al., “Elevated relative ﬂuorescence intensity of CD38 antigen expression on CD8+ T cells is a marker of poor prognosis in HIV infection: results of 6 years of follow-up,” Cytometry, vol. 26, no. 1, pp. 1–7, 1996. [68] J. V. Giorgi, Z. Liu, L. E. Hultin, W. G. Cumberland, K. Hen- nessey, and R. Detels, “Elevated levels of CD38+ CD8+ T cells in HIV infection add to the prognostic value of low CD4+ T cell levels: results of 6 years of follow-up. The Los Angeles Center, Multicenter AIDS Cohort Study,” Journal of Acquired Immune Deﬁciency Syndromes, vol. 6, no. 8, pp. 904–912, 1993. [69] E. L. Pesanti, “Eﬀects of bacterial pneumonitis on devel- opment of pneumocystosis in rats,” American Review of Respiratory Disease, vol. 125, no. 6, pp. 723–726, 1982. [70] R. E. Owen, J. W. Heitman, D. F. Hirschkorn et al., “HIV+ elite controllers have low HIV-speciﬁc T-cell activation yet maintain strong, polyfunctional T-cell responses,” AIDS, vol. 24, no. 8, pp. 1095–1105, 2010. [71] P. Kamya, C. M. Tsoukas, S. Boulet et al., “T cell Activation does not drive CD4 decline in longitudinally followed HIV- infected Elite Controllers,” AIDS Research and Therapy, vol. 8, no. 1, article 20, 2011. [72] G. Bello, C. A. Velasco-de-Castro, V. Bongertz et al., “Im- mune activation and antibody responses in non-progressing elite controller individuals infected with HIV-1,” Journal of Medical Virology, vol. 81, no. 10, pp. 1681–1690, 2009. [73] P. W. Hunt, J. Brenchley, E. Sinclair et al., “Relationship between T cell activation and CD4+ T cell count in HIV- seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy,” Journal of Infectious Diseases, vol. 197, no. 1, pp. 126–133, 2008. [74] J. Carbone, J. Gil, J. M. Benito, and E. Fernandez-Cruz, “Decreased expression of activation markers on CD4 T lym- phocytes of HIV-infected long-term non-progressors,” AIDS, vol. 17, no. 1, pp. 133–134, 2003. [75] S. R. Broussard, S. I. Staprans, R. White, E. M. Whitehead, M. B. Feinberg, and J. S. Allan, “Simian immunodeﬁciency virus replicates to high levels in naturally infected African green monkeys without inducing immunologic or neurologic disease,” Journal of Virology, vol. 75, no. 5, pp. 2262–2275, 2001. [76] A. Kaur, R. M. Grant, R. E. Means, H. Mcclure, M. Feinberg, and R. P. Johnson, “Diverse host responses and outcomes fol- lowing simian immunodeﬁciency virus SIVmac239 infection