8 ability to produce cells or a lower rate of destruction is expected in these patients according to the preservation of normal CD4+ cell counts. However, increased rate of production has not been shown so far, and the ﬁnding of similar levels of IL-7 between LTNP and progressors suggests that a diﬀerent CD4+ production is not the explanation for non-progression in LTNP. Likewise, evidence of reduced turnover of cells in LTNP has not been found, and in general LTNPs appear to have an immune system very much like progressors. However, ﬁndings of elevated levels of Th17 cells have been reported, suggesting that the immune regulation by pro- and anti-inﬂammatory cells is diﬀerent in LTNP compared to progressors. Indeed, it would be interesting to further evaluate immunological parameters, includingTh17 cells, Tregs, and microbial translocation in LTNP, ideally in prospective studies in order to clarify cause and eﬀect. Also, it would be of interest to elucidate immunological param- eters in former LTNP who have lost their non-progressor status. Finally, due to distinct immunologically proﬁles in LTNP and controllers, we suggest that a clear distinction between patients with and without viral replication is made in future studies in order to improve the possibility to understand the diﬀerent mechanisms for non-progression in these fascinating patients. Conﬂict of Interests The authors have no conﬂicts to disclose. Acknowledgments The authors thank the Novo Nordisk Foundation and University of Copenhagen for ﬁnancial support. References [1] M. Mikhail, B. Wang, and N. K. Saksena, “Mechanisms involved in non-progressive HIV disease,” AIDS Reviews, vol. 5, no. 4, pp. 230–244, 2003. [2] Y. Madec, F. Boufassa, K. Porter, and L. Meyer, “Spontaneous control of viral load and CD4 cell count progression among HIV-1 seroconverters,” AIDS, vol. 19, no. 17, pp. 2001–2007, 2005. [3] M. Dean, M. Carrington, C. Winkler et al., “Genetic restric- tion of HIV-1 infection and progression to AIDS by a dele- tion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study,” Science, vol. 273, no. 5283, pp. 1856– 1862, 1996. [4] J. Eugen-Olsen, A. K. N. Iversen, P. Garred et al., “Heterozy- gosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals,” AIDS, vol. 11, no. 3, pp. 305–310, 1997. [5] M. R. Klein, S. H. Van Der Burg, E. Hovenkamp et al., “Characterization of HLA-B57-restricted human immun- odeﬁciency virus type 1 Gag- and RT-speciﬁc cytotoxic T lymphocyte responses,” Journal of General Virology, vol. 79, no. 9, pp. 2191–2201, 1998. AIDS Research and Treatment [6] L. Piacentini, M. Biasin, C. Fenizia, and M. Clerici, “Genetic correlates of protection against HIV infection: the ally within,” Journal of Internal Medicine, vol. 265, no. 1, pp. 110– 124, 2009. [7] J. Fellay, K. V. Shianna, D. Ge et al., “A whole-genome associ- ation study of major determinants for host control of HIV-1,” Science, vol. 317, no. 5840, pp. 944–947, 2007. [8] E. Ruiz-Mateos, S. Ferrando-Martinez, K. Machmach et al., “High levels of CD57+CD28−T-cells, low T-cell proliferation and preferential expansion of terminally diﬀerentiated CD4+ T-cells in HIV-Elite controllers,” Current HIV Research, vol. 8, no. 6, pp. 471–481, 2010. [9] F. Pereyra, X. Jia, P. J. McLaren, A. Telenti, P. I. W. De Bakker, and B. D. Walker, “The major genetic determinants of HIV-1 control aﬀect HLA class I peptide presentation,” Science, vol. 330, no. 6010, pp. 1551–1557, 2010. [10] K. Poropatich and D. J. Sullivan, “Human immunodeﬁciency virus type 1 long-term non-progressors: the viral, genetic and immunological basis for disease non-progression,” Journal of General Virology, vol. 92, no. 2, pp. 247–268, 2011. [11] F. Kirchhoﬀ, T. C. Greenough, D. B. Brettler, J. L. Sullivan, and R. C. Desrosiers, “Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV- 1 infection,” New England Journal of Medicine, vol. 332, no. 4, pp. 228–232, 1995. [12] R. Mariani, F. Kirchhoﬀ, T. C. Greenough, J. L. Sullivan, R. C. Desrosiers, and J. Skowronski, “High frequency of defective nef alleles in a long-term survivor with nonprogressive human immunodeﬁciency virus type 1 infection,” Journal of Virology, vol. 70, no. 11, pp. 7752–7764, 1996. [13] A. K. N. Iversen, E. G. Shpaer, A. G. Rodrigo et al., “Persis- tence of attenuated rev genes in a human immunodeﬁciency virus type 1-infected asymptomatic individual,” Journal of Virology, vol. 69, no. 9, pp. 5743–5753, 1995. [14] N. J. Deacon, A. Tsykin, A. Solomon et al., “Genomic struc- ture of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients,” Science, vol. 270, no. 5238, pp. 988–991, 1995. [15] J. N. Blankson, J. R. Bailey, S. Thayil et al., “Isolation and characterization of replication-competent human immun- odeﬁciency virus type 1 from a subset of elite suppressors,” Journal of Virology, vol. 81, no. 5, pp. 2508–2518, 2007. [16] J. R. Bailey, K. O’Connell, H. C. Yang et al., “Transmission of human immunodeﬁciency virus type 1 from a patient who developed AIDS to an elite suppressor,” Journal of Virology, vol. 82, no. 15, pp. 7395–7410, 2008. [17] B. Julg, F. Pereyra, M. J. Buzo´ n et al., “Infrequent recovery of HIV from but robust exogenous infection of activated CD4+ T Cells in HIV Elite Controllers,” Clinical Infectious Diseases, vol. 51, no. 2, pp. 233–238, 2010. [18] H. Chen, C. Li, J. Huang et al., “CD4+ T cells from elite controllers resist HIV-1 infection by selective upregulation of p21,” Journal of Clinical Investigation, vol. 121, no. 4, pp. 1549–1560, 2011. [19] S. A. Rabi, K. A. O’Connell, D. Nikolaeva et al., “Unstimu- lated primary CD4+ T cells from HIV-1-positive elite sup- pressors are fully susceptible to HIV-1 entry and productive infection,” Journal of Virology, vol. 85, no. 2, pp. 979–986, 2011. [20] E. Ruiz-Mateos, K. MacHmach, M. C. Romero-Sanchez et al., “Hepatitis C virus replication in caucasian HIV controllers,” Journal of Viral Hepatitis, vol. 18, no. 7, pp. e350–e357, 2011.