• 1
    Chun, T. W., Justement, J. S., Murray, D., Hallahan, C. W., Maenza, J., Collier, A. C., Sheth, P. M. et al., Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication. AIDS 2010. 24: 28032808.
  • 2
    Palella, F. J., Jr., Delaney, K. M., Moorman, A. C., Loveless, M. O., Fuhrer, J., Satten, G. A., Aschman, D. J. et al., Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV outpatient study investigators. New Engl. J. Med. 1998. 338: 853860.
  • 3
    Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 2008. 372: 293299.
  • 4
    Lewden, C., Chene, G., Morlat, P., Raffi, F., Dupon, M., Dellamonica, P., Pellegrin, J. L. et al., HIV-infected adults with a CD4 cell count greater than 500 cells/mm3 on long-term combination antiretroviral therapy reach same mortality rates as the general population. J. Acquir. Immune Defic. Syndr. 2007. 46: 7277.
  • 5
    Davey, R. T., Jr., Bhat, N., Yoder, C., Chun, T. W., Metcalf, J. A., Dewar, R., Natarajan, V. et al., HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc. Natl. Acad. Sci. USA 1999. 96: 1510915114.
  • 6
    Oxenius, A., Price, D. A., Gunthard, H. F., Dawson, S. J., Fagard, C., Perrin, L., Fischer, M. et al., Stimulation of HIV-specific cellular immunity by structured treatment interruption fails to enhance viral control in chronic HIV infection. Proc. Natl. Acad. Sci. USA 2002. 99: 1374713752.
  • 7
    Ortiz, G. M., Wellons, M., Brancato, J., Vo, H. T., Zinn, R. L., Clarkson, D. E., Van Loon, K. et al., Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects. Proc. Natl. Acad. Sci. USA 2001. 98: 1328813293.
  • 8
    Autran, B. and Carcelain, G., AIDS. Boosting immunity to HIV—can the virus help? Science 2000. 290: 946949.
  • 9
    Wang, H. B., Kondo, A., Yoshida, A., Yoshizaki, S., Abe, S., Bao, L. L., Mizuki, N. et al., Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys. Gene Ther. 2010. 17: 413.
  • 10
    Hel, Z., Venzon, D., Poudyal, M., Tsai, W. P., Giuliani, L., Woodward, R., Chougnet, C. et al., Viremia control following antiretroviral treatment and therapeutic immunization during primary SIV251 infection of macaques. Nat. Med. 2000. 6: 11401146.
  • 11
    Angel, J. B., Routy, J. P., Tremblay, C., Ayers, D., Woods, R., Singer, J., Bernard, N. et al., A randomized controlled trial of HIV therapeutic vaccination using ALVAC with or without Remune. AIDS 2011. 25: 731739.
  • 12
    Autran, B., Carcelain, G., Combadiere, B. and Debre, P., Therapeutic vaccines for chronic infections. Science 2004. 305: 205208.
  • 13
    Levy, Y., Durier, C., Lascaux, A. S., Meiffredy, V., Gahery-Segard, H., Goujard, C., Rouzioux, C. et al., Sustained control of viremia following therapeutic immunization in chronically HIV-1-infected individuals. AIDS 2006. 20: 405413.
  • 14
    Schooley, R. T., Spino, C., Kuritzkes, D., Walker, B. D., Valentine, F. A., Hirsch, M. S., Cooney, E. et al., Two double-blinded, randomized, comparative trials of 4 human immunodeficiency virus type 1 (HIV-1) envelope vaccines in HIV-1-infected individuals across a spectrum of disease severity: AIDS clinical trials groups 209 and 214. J. Infect. Dis. 2000. 182: 13571364.
  • 15
    Kran, A. M., Sommerfelt, M. A., Sorensen, B., Nyhus, J., Baksaas, I., Bruun, J. N. and Kvale, D., Reduced viral burden amongst high responder patients following HIV-1 p24 peptide-based therapeutic immunization. Vaccine 2005. 23: 40114015.
  • 16
    Kinloch-de Loes, S., Hoen, B., Smith, D. E., Autran, B., Lampe, F. C., Phillips, A. N., Goh, L. E. et al., Impact of therapeutic immunization on HIV-1 viremia after discontinuation of antiretroviral therapy initiated during acute infection. J. Infect. Dis. 2005. 192: 607617.
  • 17
    Fernandez-Cruz, E., Moreno, S., Navarro, J., Clotet, B., Bouza, E., Carbone, J., Pena, J. M. et al., Therapeutic immunization with an inactivated HIV-1 immunogen plus antiretrovirals versus antiretroviral therapy alone in asymptomatic HIV-infected subjects. Vaccine 2004. 22: 29662973.
  • 18
    Goujard, C., Marcellin, F., Hendel-Chavez, H., Burgard, M., Meiffredy, V., Venet, A., Rouzioux, C. et al., Interruption of antiretroviral therapy initiated during primary HIV-1 infection: impact of a therapeutic vaccination strategy combined with interleukin (IL)-2 compared with IL-2 alone in the ANRS 095 randomized study. AIDS Res. Hum. Retroviruses 2007. 23: 11051113.
  • 19
    Levy, Y., Gahery-Segard, H., Durier, C., Lascaux, A. S., Goujard, C., Meiffredy, V., Rouzioux, C. et al., Immunological and virological efficacy of a therapeutic immunization combined with interleukin-2 in chronically HIV-1 infected patients. AIDS 2005. 19: 279286.
  • 20
    Casazza, J., Bowman, K., Ambrozak, D., Gordon, I., Roederer, M., Enama, M., Nason, M. et al., Increased HIV-specific immunity in HIV-infected individuals vaccinated with a DNA prime, rAd5 boost regimen CROI 2010.
  • 21
    Li, J. Z., Brumme, Z. L., Brumme, C. J., Wang, H., Spritzler, J., Robertson, M. N., Lederman, M. M. et al., Factors associated with viral rebound in HIV-1-infected individuals enrolled in a therapeutic HIV-1 gag vaccine trial. J. Infect. Dis. 2011. 203: 976983.
  • 22
    Autran, B., Murphy, R. L., Costagliola, D., Tubiana, R., Clotet, B., Gatell, J., Staszewski, S. et al., Greater viral rebound and reduced time to resume antiretroviral therapy after therapeutic immunization with the ALVAC-HIV vaccine (vCP1452). AIDS 2008. 22: 13131322.
  • 23
    Papagno, L., Alter, G., Assoumou, L., Murphy, R. L., Garcia, F., Clotet, B., Larsen, M. et al., Comprehensive analysis of virus-specific T-cells provides clues for the failure of therapeutic immunization with ALVAC-HIV vaccine. AIDS 2011. 25: 2736.
  • 24
    Zimmerli, S. C., Harari, A., Cellerai, C., Vallelian, F., Bart, P. A. and Pantaleo, G., HIV-1-specific IFN-gamma/IL-2-secreting CD8 T cells support CD4-independent proliferation of HIV-1-specific CD8 T cells. Proc. Natl. Acad. Sci. USA 2005. 102: 72397244.
  • 25
    Betts, M. R., Nason, M. C., West, S. M., De Rosa, S. C., Migueles, S. A., Abraham, J., Lederman, M. M. et al., HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 2006. 107: 47814789.
  • 26
    Seder, R. A., Darrah, P. A. and Roederer, M., T-cell quality in memory and protection: implications for vaccine design. Nat. Rev. Immunol. 2008. 8: 247258.
  • 27
    Kiepiela, P., Ngumbela, K., Thobakgale, C., Ramduth, D., Honeyborne, I., Moodley, E., Reddy, S. et al., CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat. Med. 2007. 13: 4653.
  • 28
    Puissant-Lubrano, B., Combadiere, B., Duffy, D., Wincker, N., Frachette, M. J., Ait-Mohand, H., Verrier, B. et al., Influence of antigen exposure on the loss of long-term memory to childhood vaccines in HIV-infected patients. Vaccine 2009. 27: 35763583.
  • 29
    Harari, A., Enders, F. B., Cellerai, C., Bart, P. A. and Pantaleo, G., Distinct profiles of cytotoxic granules in memory CD8 T cells correlate with function, differentiation stage, and antigen exposure. Journal Virol. 2009. 83: 28622871.
  • 30
    Bart, P. A., Harari, A. and Pantaleo, G., Clinical studies of experimental vaccines. Curr. Opin. HIV AIDS 2006. 1: 286293.
  • 31
    Betts, M. R. and Harari, A., Phenotype and function of protective T cell immune responses in HIV. Curr. Opin. HIV AIDS 2008. 3: 349355.
  • 32
    Migueles, S. A., Laborico, A. C., Shupert, W. L., Sabbaghian, M. S., Rabin, R., Hallahan, C. W., Van Baarle, D. et al., HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat. Immun. 2002. 3: 10611068.
  • 33
    Iyasere, C., Tilton, J. C., Johnson, A. J., Younes, S., Yassine-Diab, B., Sekaly, R. P., Kwok, W. W. et al., Diminished proliferation of human immunodeficiency virus-specific CD4+ T cells is associated with diminished interleukin-2 (IL-2) production and is recovered by exogenous IL-2. J. Virol. 2003. 77: 1090010909.
  • 34
    Younes, S. A., Yassine-Diab, B., Dumont, A. R., Boulassel, M. R., Grossman, Z., Routy, J. P. and Sekaly, R. P., HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific memory CD4+ T cells endowed with proliferative capacity. J. Exp. Med. 2003. 198: 19091922.
  • 35
    Spentzou, A., Bergin, P., Gill, D., Cheeseman, H., Ashraf, A., Kaltsidis, H., Cashin-Cox, M. et al., Viral inhibition assay: a CD8 T cell neutralization assay for use in clinical trials of HIV-1 vaccine candidates. J. Infect. Dis. 2010. 201: 720729.
  • 36
    Yang, H., Wu, H., Hancock, G., Clutton, G., Sande, N., Xu, X., Yan, H., Huang, X., Angus, B., Kuldanek, K., Fidler, S., Denny, TN., Birks, J., McMichael, A., Dorrell, L., Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection. J Infect Dis 2012. 206: 552561.
  • 37
    Freel, S. A., Picking, R. A., Ferrari, G., Ding, H., Ochsenbauer, C., Kappes, J. C., Kirchherr, J. L. et al., Initial HIV-1 antigen-specific CD8 +T cells in acute HIV-1 infection inhibit transmitted/founder virus replication. J. Virol. 2012. 86: 68356846.
  • 38
    Freel, S. A., Lamoreaux, L., Chattopadhyay, P. K., Saunders, K., Zarkowsky, D., Overman, R. G., Ochsenbauer, C. et al., Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination. J. Virol. 2010. 84: 49985006.
  • 39
    Persaud, D., Luzuriaga, K., Ziemniak, C., Muresan, P., Greenough, T., Fenton, T., Blackford, A. et al., Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir. AIDS 2011. 25: 22272234.
  • 40
    El-Sadr, W. M., Lundgren, J. D., Neaton, J. D., Gordin, F., Abrams, D., Arduino, R. C., Babiker, A. et al., CD4+ count-guided interruption of antiretroviral treatment. New Engl. J. Med. 2006. 355: 22832296.
  • 41
    Skiest, D. J., Krambrink, A., Su, Z., Robertson, K. R. and Margolis, D. M., Improved measures of quality of life, lipid profile, and lipoatrophy after treatment interruption in HIV-infected patients with immune preservation: results of ACTG 5170. J. Acquir. Immune Defic. Syndr. 2008. 49: 377383.
  • 42
    Combadiere, B., Boissonnas, A., Carcelain, G., Lefranc, E., Samri, A., Bricaire, F., Debre, P. et al., Distinct time effects of vaccination on long-term proliferative and IFN-gamma-producing T cell memory to smallpox in humans. J. Exp. Med. 2004. 199: 15851593.
  • 43
    Leparc-Goffart, I., Poirier, B., Garin, D., Tissier, M. H., Fuchs, F. and Crance, J. M., Standardization of a neutralizing anti-vaccinia antibodies titration method: an essential step for titration of vaccinia immunoglobulins and smallpox vaccines evaluation. J. Clin. Virol. 2005. 32: 4752.
  • 44
    Gomez, C. E., Najera, J. L., Jimenez, E. P., Jimenez, V., Wagner, R., Graf, M., Frachette, M. J. et al., Head-to-head comparison on the immunogenicity of two HIV/AIDS vaccine candidates based on the attenuated poxvirus strains MVA and NYVAC co-expressing in a single locus the HIV-1BX08 gp120 and HIV-1(IIIB) Gag-Pol-Nef proteins of clade B. Vaccine 2007. 25: 28632885.
  • 45
    Frahm, N. and Brander, C., Optimal CTL epitope identification in HIV clade B and non-clade B infection. HIV Mol. Immunol. 2005: 320.
  • 46
    Currier, J. R., Kuta, E. G., Turk, E., Earhart, L. B., Loomis-Price, L., Janetzki, S., Ferrari, G. et al., A panel of MHC class I restricted viral peptides for use as a quality control for vaccine trial ELISPOT assays. J. Immunol. Methods 2002. 260: 157172.
  • 47
    Harari, A., Bart, P. A., Stohr, W., Tapia, G., Garcia, M., Medjitna-Rais, E., Burnet, S. et al., An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses. J. Exp. Med. 2008. 205: 6377.
  • 48
    Cellerai, C., Perreau, M., Rozot, V., Enders, F. B., Pantaleo, G. and Harari, A., Proliferation capacity and cytotoxic activity are mediated by functionally and phenotypically distinct virus-specific CD8 T cells defined by interleukin-7R{alpha} (CD127) and perforin expression. J. Virol. 2010. 84: 38683878.
  • 49
    Roederer, M., Nozzi, J. L. and Nason, M. C., SPICE: exploration and analysis of post-cytometric complex multivariate datasets. Cytometry A 2011. 79A: 167174.