Background In most subjects infected with human immunodeficiencyvirus type 1 (HIV-1), clinical or laboratory evidence of immunodeficiencydevelops within 10 years of seroconversion, but a few infectedpeople remain healthy and immunologically normal for more thana decade. Studies of these subjects, termed long-term survivors,may yield important clues for the development of prophylacticand therapeutic interventions against the acquired immunodeficiencysyndrome.
Methods and Results We studied 10 seropositive subjects whoremained asymptomatic with normal and stable CD4+ lymphocytecounts despite 12 to 15 years of HIV-1 infection. Plasma cultureswere uniformly negative for infectious virus. However, particle-associatedHIV-1 RNA was detected in four subjects with a sensitive branched-DNAsignal-amplification assay, whereas in five others the levelsof HIV-1 RNA were too low to detect. Infectious HIV-1 was detectedin peripheral-blood mononuclear cells (PBMC) of three subjectsby standard limiting-dilution cultures, and infectious viruswas recovered from another subject with use of a CD8-depletedculture. The other six subjects had no detectable infectiousvirus in their PBMC. A quantitative polymerase-chain-reactionassay revealed that all subjects had detectable but low titersof viral DNA in PBMC. Overall, the viral burden in the plasmaand PBMC of long-term survivors was orders of magnitude lowerthan that typically found in subjects with progressive disease.
There was no in vitro evidence of resistance by host CD4+ lymphocytesto HIV-1 infection. However, long-term survivors had a vigorous,virus-inhibitory CD8+ lymphocyte response and a strong neutralizing-antibodyresponse. In two subjects the kinetics of viral replicationwas consistent with the presence of a substantially attenuatedstrain of HIV-1.
Conclusions Subjects who remain asymptomatic for many yearsdespite HIV-1 infection have low levels of HIV-1 and a combinationof strong virus-specific immune responses with some degree ofattenuation of the virus.
Source Information
From the Aaron Diamond AIDS Research Center, New York University School of Medicine, 455 First Ave., New York, NY 10016, where reprint requests should be addressed to Dr. Ho.
Miura, T., Brockman, M. A., Brumme, C. J., Brumme, Z. L., Carlson, J. M., Pereyra, F., Trocha, A., Addo, M. M., Block, B. L., Rothchild, A. C., Baker, B. M., Flynn, T., Schneidewind, A., Li, B., Wang, Y. E., Heckerman, D., Allen, T. M., Walker, B. D.
(2008). Genetic Characterization of Human Immunodeficiency Virus Type 1 in Elite Controllers: Lack of Gross Genetic Defects or Common Amino Acid Changes. J. Virol.
82: 8422-8430
[Abstract][Full Text]
Chase, A. J., Yang, H.-C., Zhang, H., Blankson, J. N., Siliciano, R. F.
(2008). Preservation of FoxP3+ Regulatory T Cells in the Peripheral Blood of Human Immunodeficiency Virus Type 1-Infected Elite Suppressors Correlates with Low CD4+ T-Cell Activation. J. Virol.
82: 8307-8315
[Abstract][Full Text]
Bunnik, E. M., Pisas, L., van Nuenen, A. C., Schuitemaker, H.
(2008). Autologous Neutralizing Humoral Immunity and Evolution of the Viral Envelope in the Course of Subtype B Human Immunodeficiency Virus Type 1 Infection. J. Virol.
82: 7932-7941
[Abstract][Full Text]
Shanmugasundaram, U., Murugavel, K. G., Shankar, E. M., Balakrishnan, P., Solomon, S., Kumarasamy, N.
(2008). Laboratory characteristics of HIV-1 clade C-infected long-term non-progressors at a tertiary human immunodeficiency virus care centre in South India. J Med Microbiol
57: 913-915
[Full Text]
Halwani, R., Boyer, J. D., Yassine-Diab, B., Haddad, E. K., Robinson, T. M., Kumar, S., Parkinson, R., Wu, L., Sidhu, M. K., Phillipson-Weiner, R., Pavlakis, G. N., Felber, B. K., Lewis, M. G., Shen, A., Siliciano, R. F., Weiner, D. B., Sekaly, R.-P.
(2008). Therapeutic Vaccination with Simian Immunodeficiency Virus (SIV)-DNA+IL-12 or IL-15 Induces Distinct CD8 Memory Subsets in SIV-Infected Macaques. J. Immunol.
180: 7969-7979
[Abstract][Full Text]
Torian, L. V., Wiewel, E. W., Liu, K.-L., Sackoff, J. E., Frieden, T. R.
(2008). Risk Factors for Delayed Initiation of Medical Care After Diagnosis of Human Immunodeficiency Virus. Arch Intern Med
168: 1181-1187
[Abstract][Full Text]
Wilson, C. C., Newman, M. J., Livingston, B. D., MaWhinney, S., Forster, J. E., Scott, J., Schooley, R. T., Benson, C. A.
(2008). Clinical Phase 1 Testing of the Safety and Immunogenicity of an Epitope-Based DNA Vaccine in Human Immunodeficiency Virus Type 1-Infected Subjects Receiving Highly Active Antiretroviral Therapy. CVI
15: 986-994
[Abstract][Full Text]
Emu, B., Sinclair, E., Hatano, H., Ferre, A., Shacklett, B., Martin, J. N., McCune, J. M., Deeks, S. G.
(2008). HLA Class I-Restricted T-Cell Responses May Contribute to the Control of Human Immunodeficiency Virus Infection, but Such Responses Are Not Always Necessary for Long-Term Virus Control. J. Virol.
82: 5398-5407
[Abstract][Full Text]
Schoenly, K. A., Weiner, D. B.
(2008). Human Immunodeficiency Virus Type 1 Vaccine Development: Recent Advances in the Cytotoxic T-Lymphocyte Platform "Spotty Business". J. Virol.
82: 3166-3180
[Full Text]
Dykes, C., Demeter, L. M.
(2007). Clinical Significance of Human Immunodeficiency Virus Type 1 Replication Fitness. Clin. Microbiol. Rev.
20: 550-578
[Abstract][Full Text]
Milush, J. M., Stefano-Cole, K., Schmidt, K., Durudas, A., Pandrea, I., Sodora, D. L.
(2007). Mucosal Innate Immune Response Associated with a Timely Humoral Immune Response and Slower Disease Progression after Oral Transmission of Simian Immunodeficiency Virus to Rhesus Macaques. J. Virol.
81: 6175-6186
[Abstract][Full Text]
Rodriguez, S. K., Sarr, A. D., MacNeil, A., Thakore-Meloni, S., Gueye-Ndiaye, A., Traore, I., Dia, M. C., Mboup, S., Kanki, P. J.
(2007). Comparison of Heterologous Neutralizing Antibody Responses of Human Immunodeficiency Virus Type 1 (HIV-1)- and HIV-2-Infected Senegalese Patients: Distinct Patterns of Breadth and Magnitude Distinguish HIV-1 and HIV-2 Infections. J. Virol.
81: 5331-5338
[Abstract][Full Text]
Priceputu, E., Hanna, Z., Hu, C., Simard, M.-C., Vincent, P., Wildum, S., Schindler, M., Kirchhoff, F., Jolicoeur, P.
(2007). Primary Human Immunodeficiency Virus Type 1 Nef Alleles Show Major Differences in Pathogenicity in Transgenic Mice. J. Virol.
81: 4677-4693
[Abstract][Full Text]
Saez-Cirion, A., Lacabaratz, C., Lambotte, O., Versmisse, P., Urrutia, A., Boufassa, F., Barre-Sinoussi, F., Delfraissy, J.-F., Sinet, M., Pancino, G., Venet, A., for the Agence Nationale de Recherches sur le Sida,
(2007). HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc. Natl. Acad. Sci. USA
104: 6776-6781
[Abstract][Full Text]
Shibata, J., Yoshimura, K., Honda, A., Koito, A., Murakami, T., Matsushita, S.
(2007). Impact of V2 Mutations on Escape from a Potent Neutralizing Anti-V3 Monoclonal Antibody during In Vitro Selection of a Primary Human Immunodeficiency Virus Type 1 Isolate. J. Virol.
81: 3757-3768
[Abstract][Full Text]
Hyrcza, M. D., Kovacs, C., Loutfy, M., Halpenny, R., Heisler, L., Yang, S., Wilkins, O., Ostrowski, M., Der, S. D.
(2007). Distinct Transcriptional Profiles in Ex Vivo CD4+ and CD8+ T Cells Are Established Early in Human Immunodeficiency Virus Type 1 Infection and Are Characterized by a Chronic Interferon Response as Well as Extensive Transcriptional Changes in CD8+ T Cells. J. Virol.
81: 3477-3486
[Abstract][Full Text]
Blankson, J. N., Bailey, J. R., Thayil, S., Yang, H.-C., Lassen, K., Lai, J., Gandhi, S. K., Siliciano, J. D., Williams, T. M., Siliciano, R. F.
(2007). Isolation and Characterization of Replication-Competent Human Immunodeficiency Virus Type 1 from a Subset of Elite Suppressors. J. Virol.
81: 2508-2518
[Abstract][Full Text]
Rutjens, E., Mazza, S., Biassoni, R., Koopman, G., Radic, L., Fogli, M., Costa, P., Mingari, M. C., Moretta, L., Heeney, J., De Maria, A.
(2007). Differential NKp30 Inducibility in Chimpanzee NK Cells and Conserved NK Cell Phenotype and Function in Long-Term HIV-1-Infected Animals. J. Immunol.
178: 1702-1712
[Abstract][Full Text]
Nilsson, J., Boasso, A., Velilla, P. A., Zhang, R., Vaccari, M., Franchini, G., Shearer, G. M., Andersson, J., Chougnet, C.
(2006). HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS. Blood
108: 3808-3817
[Abstract][Full Text]
Titanji, K., De Milito, A., Cagigi, A., Thorstensson, R., Grutzmeier, S., Atlas, A., Hejdeman, B., Kroon, F. P., Lopalco, L., Nilsson, A., Chiodi, F.
(2006). Loss of memory B cells impairs maintenance of long-term serologic memory during HIV-1 infection. Blood
108: 1580-1587
[Abstract][Full Text]
Pastori, C., Weiser, B., Barassi, C., Uberti-Foppa, C., Ghezzi, S., Longhi, R., Calori, G., Burger, H., Kemal, K., Poli, G., Lazzarin, A., Lopalco, L.
(2006). Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression. Blood
107: 4825-4833
[Abstract][Full Text]
Bailey, J. R., Williams, T. M., Siliciano, R. F., Blankson, J. N.
(2006). Maintenance of viral suppression in HIV-1-infected HLA-B*57+ elite suppressors despite CTL escape mutations. J. Exp. Med.
203: 1357-1369
[Abstract][Full Text]
Bailey, J. R., Lassen, K. G., Yang, H.-C., Quinn, T. C., Ray, S. C., Blankson, J. N., Siliciano, R. F.
(2006). Neutralizing antibodies do not mediate suppression of human immunodeficiency virus type 1 in elite suppressors or selection of plasma virus variants in patients on highly active antiretroviral therapy.. J. Virol.
80: 4758-4770
[Abstract][Full Text]
Lauren, A., Thorstensson, R., Fenyo, E. M.
(2006). Comparative studies on mucosal and intravenous transmission of simian immunodeficiency virus (SIVsm): the kinetics of evolution to neutralization resistance are related to progression rate of disease.. J. Gen. Virol.
87: 595-606
[Abstract][Full Text]
Speelmon, E. C., Livingston-Rosanoff, D., Li, S. S., Vu, Q., Bui, J., Geraghty, D. E., Zhao, L. P., McElrath, M. J.
(2006). Genetic Association of the Antiviral Restriction Factor TRIM5{alpha} with Human Immunodeficiency Virus Type 1 Infection. J. Virol.
80: 2463-2471
[Abstract][Full Text]
Blay, W.M., Gnanakaran, S., Foley, B., Doria-Rose, N. A., Korber, B. T., Haigwood, N. L.
(2006). Consistent Patterns of Change during the Divergence of Human Immunodeficiency Virus Type 1 Envelope from That of the Inoculated Virus in Simian/Human Immunodeficiency Virus-Infected Macaques. J. Virol.
80: 999-1014
[Abstract][Full Text]
Skrabal, K., Saragosti, S., Labernardiere, J.-L., Barin, F., Clavel, F., Mammano, F.
(2005). Human Immunodeficiency Virus Type 1 Variants Isolated from Single Plasma Samples Display a Wide Spectrum of Neutralization Sensitivity. J. Virol.
79: 11848-11857
[Abstract][Full Text]
Doria-Rose, N. A., Learn, G. H., Rodrigo, A. G., Nickle, D. C., Li, F., Mahalanabis, M., Hensel, M. T., McLaughlin, S., Edmonson, P. F., Montefiori, D., Barnett, S. W., Haigwood, N. L., Mullins, J. I.
(2005). Human Immunodeficiency Virus Type 1 Subtype B Ancestral Envelope Protein Is Functional and Elicits Neutralizing Antibodies in Rabbits Similar to Those Elicited by a Circulating Subtype B Envelope. J. Virol.
79: 11214-11224
[Abstract][Full Text]
Jin, X., Brooks, A., Chen, H., Bennett, R., Reichman, R., Smith, H.
(2005). APOBEC3G/CEM15 (hA3G) mRNA Levels Associate Inversely with Human Immunodeficiency Virus Viremia. J. Virol.
79: 11513-11516
[Abstract][Full Text]
Rusert, P., Kuster, H., Joos, B., Misselwitz, B., Gujer, C., Leemann, C., Fischer, M., Stiegler, G., Katinger, H., Olson, W. C., Weber, R., Aceto, L., Gunthard, H. F., Trkola, A.
(2005). Virus Isolates during Acute and Chronic Human Immunodeficiency Virus Type 1 Infection Show Distinct Patterns of Sensitivity to Entry Inhibitors. J. Virol.
79: 8454-8469
[Abstract][Full Text]
Chakraborty, R., Morel, A.-S., Sutton, J. K., Appay, V., Ripley, R. M., Dong, T., Rostron, T., Ogola, S., Palakudy, T., Musoke, R., D'Agostino, A., Ritter, M., Rowland-Jones, S. L.
(2005). Correlates of Delayed Disease Progression in HIV-1-Infected Kenyan Children. J. Immunol.
174: 8191-8199
[Abstract][Full Text]
Bello, G., Casado, C., Sandonis, V., Alonso-Nieto, M., Vicario, J. L., Garcia, S., Hernando, V., Rodriguez, C., Romero, J. d., Lopez-Galindez, C.
(2005). A subset of human immunodeficiency virus type 1 long-term non-progressors is characterized by the unique presence of ancestral sequences in the viral population. J. Gen. Virol.
86: 355-364
[Abstract][Full Text]
Dacheux, L., Moreau, A., Ataman-Onal, Y., Biron, F., Verrier, B., Barin, F.
(2004). Evolutionary Dynamics of the Glycan Shield of the Human Immunodeficiency Virus Envelope during Natural Infection and Implications for Exposure of the 2G12 Epitope. J. Virol.
78: 12625-12637
[Abstract][Full Text]
Ritola, K., Pilcher, C. D., Fiscus, S. A., Hoffman, N. G., Nelson, J. A. E., Kitrinos, K. M., Hicks, C. B., Eron, J. J. Jr., Swanstrom, R.
(2004). Multiple V1/V2 env Variants Are Frequently Present during Primary Infection with Human Immunodeficiency Virus Type 1. J. Virol.
78: 11208-11218
[Abstract][Full Text]
Trkola, A., Kuster, H., Leemann, C., Oxenius, A., Fagard, C., Furrer, H., Battegay, M., Vernazza, P., Bernasconi, E., Weber, R., Hirschel, B., Bonhoeffer, S., Gunthard, H. F.
(2004). Humoral immunity to HIV-1: kinetics of antibody responses in chronic infection reflects capacity of immune system to improve viral set point. Blood
104: 1784-1792
[Abstract][Full Text]
Zhang, H., Huang, Y., Fayad, R., Spear, G. T., Qiao, L.
(2004). Induction of Mucosal and Systemic Neutralizing Antibodies against Human Immunodeficiency Virus Type 1 (HIV-1) by Oral Immunization with Bovine Papillomavirus-HIV-1 gp41 Chimeric Virus-Like Particles. J. Virol.
78: 8342-8348
[Abstract][Full Text]
Logvinoff, C., Major, M. E., Oldach, D., Heyward, S., Talal, A., Balfe, P., Feinstone, S. M., Alter, H., Rice, C. M., McKeating, J. A.
(2004). Neutralizing antibody response during acute and chronic hepatitis C virus infection. Proc. Natl. Acad. Sci. USA
101: 10149-10154
[Abstract][Full Text]
Beaumont, T., Quakkelaar, E., van Nuenen, A., Pantophlet, R., Schuitemaker, H.
(2004). Increased Sensitivity to CD4 Binding Site-Directed Neutralization following In Vitro Propagation on Primary Lymphocytes of a Neutralization-Resistant Human Immunodeficiency Virus IIIB Strain Isolated from an Accidentally Infected Laboratory Worker. J. Virol.
78: 5651-5657
[Abstract][Full Text]
Mason, R. D., Bowmer, M. I., Howley, C. M., Gallant, M., Myers, J. C. E., Grant, M. D.
(2004). Antiretroviral Drug Resistance Mutations Sustain or Enhance CTL Recognition of Common HIV-1 Pol Epitopes. J. Immunol.
172: 7212-7219
[Abstract][Full Text]
Samino, Y., Lopez, D., Guil, S., de Leon, P., Del Val, M.
(2004). An Endogenous HIV Envelope-derived Peptide without the Terminal NH3+ Group Anchor Is Physiologically Presented by Major Histocompatibility Complex Class I Molecules. J. Biol. Chem.
279: 1151-1160
[Abstract][Full Text]
Hirsch, V. M., Santra, S., Goldstein, S., Plishka, R., Buckler-White, A., Seth, A., Ourmanov, I., Brown, C. R., Engle, R., Montefiori, D., Glowczwskie, J., Kunstman, K., Wolinsky, S., Letvin, N. L.
(2004). Immune Failure in the Absence of Profound CD4+ T-Lymphocyte Depletion in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques. J. Virol.
78: 275-284
[Abstract][Full Text]
Campbell, T. B., Schneider, K., Wrin, T., Petropoulos, C. J., Connick, E.
(2003). Relationship between In Vitro Human Immunodeficiency Virus Type 1 Replication Rate and Virus Load in Plasma. J. Virol.
77: 12105-12112
[Abstract][Full Text]
Wilson, C. C., McKinney, D., Anders, M., MaWhinney, S., Forster, J., Crimi, C., Southwood, S., Sette, A., Chesnut, R., Newman, M. J., Livingston, B. D.
(2003). Development of a DNA Vaccine Designed to Induce Cytotoxic T Lymphocyte Responses to Multiple Conserved Epitopes in HIV-1. J. Immunol.
171: 5611-5623
[Abstract][Full Text]
Casartelli, N., Di Matteo, G., Potesta, M., Rossi, P., Doria, M.
(2003). CD4 and Major Histocompatibility Complex Class I Downregulation by the Human Immunodeficiency Virus Type 1 Nef Protein in Pediatric AIDS Progression. J. Virol.
77: 11536-11545
[Abstract][Full Text]
Weinberg, A., Pott, G. B.
(2003). Immunity to Human Immunodeficiency Virus (HIV) in Children with Chronic HIV Infection Receiving Highly Active Antiretroviral Therapy. CVI
10: 821-825
[Abstract][Full Text]
O'Connor, D. H., Mothe, B. R., Weinfurter, J. T., Fuenger, S., Rehrauer, W. M., Jing, P., Rudersdorf, R. R., Liebl, M. E., Krebs, K., Vasquez, J., Dodds, E., Loffredo, J., Martin, S., McDermott, A. B., Allen, T. M., Wang, C., Doxiadis, G. G., Montefiori, D. C., Hughes, A., Burton, D. R., Allison, D. B., Wolinsky, S. M., Bontrop, R., Picker, L. J., Watkins, D. I.
(2003). Major Histocompatibility Complex Class I Alleles Associated with Slow Simian Immunodeficiency Virus Disease Progression Bind Epitopes Recognized by Dominant Acute-Phase Cytotoxic-T-Lymphocyte Responses. J. Virol.
77: 9029-9040
[Abstract][Full Text]
Zhang, K., Rana, F., Silva, C., Ethier, J., Wehrly, K., Chesebro, B., Power, C.
(2003). Human Immunodeficiency Virus Type 1 Envelope-Mediated Neuronal Death: Uncoupling of Viral Replication and Neurotoxicity. J. Virol.
77: 6899-6912
[Abstract][Full Text]
Dehghani, H., Puffer, B. A., Doms, R. W., Hirsch, V. M.
(2003). Unique Pattern of Convergent Envelope Evolution in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques: Association with CD4-Independent Usage of CCR5. J. Virol.
77: 6405-6418
[Abstract][Full Text]
Montefiori, D. C., Altfeld, M., Lee, P. K., Bilska, M., Zhou, J., Johnston, M. N., Gao, F., Walker, B. D., Rosenberg, E. S.
(2003). Viremia Control Despite Escape from a Rapid and Potent Autologous Neutralizing Antibody Response After Therapy Cessation in an HIV-1-Infected Individual. J. Immunol.
170: 3906-3914
[Abstract][Full Text]
Novitsky, V., Gilbert, P., Peter, T., McLane, M. F., Gaolekwe, S., Rybak, N., Thior, I., Ndung'u, T., Marlink, R., Lee, T. H., Essex, M.
(2002). Association between Virus-Specific T-Cell Responses and Plasma Viral Load in Human Immunodeficiency Virus Type 1 Subtype C Infection. J. Virol.
77: 882-890
[Abstract][Full Text]
Boaz, M. J., Waters, A., Murad, S., Easterbrook, P. J., Vyakarnam, A.
(2002). Presence of HIV-1 Gag-Specific IFN-{gamma}+IL-2+ and CD28+IL-2+ CD4 T Cell Responses Is Associated with Nonprogression in HIV-1 Infection. J. Immunol.
169: 6376-6385
[Abstract][Full Text]
Caselli, E., Boni, M., Bracci, A., Rotola, A., Cermelli, C., Castellazzi, M., Di Luca, D., Cassai, E.
(2002). Detection of Antibodies Directed against Human Herpesvirus 6 U94/REP in Sera of Patients Affected by Multiple Sclerosis. J. Clin. Microbiol.
40: 4131-4137
[Abstract][Full Text]
Zhang, L., Yu, W., He, T., Yu, J., Caffrey, R. E., Dalmasso, E. A., Fu, S., Pham, T., Mei, J., Ho, J. J., Zhang, W., Lopez, P., Ho, D. D.
(2002). Contribution of Human alpha -Defensin 1, 2, and 3 to the Anti-HIV-1 Activity of CD8 Antiviral Factor. Science
298: 995-1000
[Abstract][Full Text]
He, Y., Honnen, W. J., Krachmarov, C. P., Burkhart, M., Kayman, S. C., Corvalan, J., Pinter, A.
(2002). Efficient Isolation of Novel Human Monoclonal Antibodies with Neutralizing Activity Against HIV-1 from Transgenic Mice Expressing Human Ig Loci. J. Immunol.
169: 595-605
[Abstract][Full Text]
Tobiume, M., Takahoko, M., Yamada, T., Tatsumi, M., Iwamoto, A., Matsuda, M.
(2002). Inefficient Enhancement of Viral Infectivity and CD4 Downregulation by Human Immunodeficiency Virus Type 1 Nef from Japanese Long-Term Nonprogressors. J. Virol.
76: 5959-5965
[Abstract][Full Text]
Chakrabarti, B. K., Kong, W.-p., Wu, B.-y., Yang, Z.-Y., Friborg, J., Ling, X., King, S. R., Montefiori, D. C., Nabel, G. J.
(2002). Modifications of the Human Immunodeficiency Virus Envelope Glycoprotein Enhance Immunogenicity for Genetic Immunization. J. Virol.
76: 5357-5368
[Abstract][Full Text]
Bures, R., Morris, L., Williamson, C., Ramjee, G., Deers, M., Fiscus, S. A., Abdool-Karim, S., Montefiori, D. C.
(2002). Regional Clustering of Shared Neutralization Determinants on Primary Isolates of Clade C Human Immunodeficiency Virus Type 1 from South Africa. J. Virol.
76: 2233-2244
[Abstract][Full Text]
Edwards, B. H., Bansal, A., Sabbaj, S., Bakari, J., Mulligan, M. J., Goepfert, P. A.
(2002). Magnitude of Functional CD8+ T-Cell Responses to the Gag Protein of Human Immunodeficiency Virus Type 1 Correlates Inversely with Viral Load in Plasma. J. Virol.
76: 2298-2305
[Abstract][Full Text]
Srivastava, I. K., Stamatatos, L., Legg, H., Kan, E., Fong, A., Coates, S. R., Leung, L., Wininger, M., Donnelly, J. J., Ulmer, J. B., Barnett, S. W.
(2002). Purification and Characterization of Oligomeric Envelope Glycoprotein from a Primary R5 Subtype B Human Immunodeficiency Virus. J. Virol.
76: 2835-2847
[Abstract][Full Text]
Makgoba, M. W., Solomon, N., Tucker, T. J. P.
(2002). Science, medicine, and the future: The search for an HIV vaccine. BMJ
324: 211-213
[Full Text]
Hiroi, T., Goto, H., Someya, K., Yanagita, M., Honda, M., Yamanaka, N., Kiyono, H.
(2001). HIV Mucosal Vaccine: Nasal Immunization with rBCG-V3J1 Induces a Long Term V3J1 Peptide-Specific Neutralizing Immunity in Th1- and Th2-Deficient Conditions. J. Immunol.
167: 5862-5867
[Abstract][Full Text]
Lawn, S. D., Butera, S. T., Folks, T. M.
(2001). Contribution of Immune Activation to the Pathogenesis and Transmission of Human Immunodeficiency Virus Type 1 Infection. Clin. Microbiol. Rev.
14: 753-777
[Abstract][Full Text]
Malenbaum, S. E., Yang, D., Cheng-Mayer, C.
(2001). Evidence for Similar Recognition of the Conserved Neutralization Epitopes of Human Immunodeficiency Virus Type 1 Envelope gp120 in Humans and Macaques. J. Virol.
75: 9287-9296
[Abstract][Full Text]
Canto-Nogues, C., Jones, S., Sangster, R., Silvera, P., Hull, R., Cook, R., Hall, G., Walker, B., Stott, E. J., Hockley, D., Almond, N.
(2001). In situ hybridization and immunolabelling study of the early replication of simian immunodeficiency virus (SIVmacJ5) in vivo. J. Gen. Virol.
82: 2225-2234
[Abstract][Full Text]
Montefiori, D. C., Safrit, J. T., Lydy, S. L., Barry, A. P., Bilska, M., Vo, H. T. T., Klein, M., Tartaglia, J., Robinson, H. L., Rovinski, B.
(2001). Induction of Neutralizing Antibodies and Gag-Specific Cellular Immune Responses to an R5 Primary Isolate of Human Immunodeficiency Virus Type 1 in Rhesus Macaques. J. Virol.
75: 5879-5890
[Abstract][Full Text]
Beaumont, T., van Nuenen, A., Broersen, S., Blattner, W. A., Lukashov, V. V., Schuitemaker, H.
(2001). Reversal of Human Immunodeficiency Virus Type 1 IIIB to a Neutralization-Resistant Phenotype in an Accidentally Infected Laboratory Worker with a Progressive Clinical Course. J. Virol.
75: 2246-2252
[Abstract][Full Text]
Broussard, S. R., Staprans, S. I., White, R., Whitehead, E. M., Feinberg, M. B., Allan, J. S.
(2001). Simian Immunodeficiency Virus Replicates to High Levels in Naturally Infected African Green Monkeys without Inducing Immunologic or Neurologic Disease. J. Virol.
75: 2262-2275
[Abstract][Full Text]
Goldstein, S., Ourmanov, I., Brown, C. R., Beer, B. E., Elkins, W. R., Plishka, R., Buckler-White, A., Hirsch, V. M.
(2000). Wide Range of Viral Load in Healthy African Green Monkeys Naturally Infected with Simian Immunodeficiency Virus. J. Virol.
74: 11744-11753
[Abstract][Full Text]
Andersson, S., Norrgren, H., da Silva, Z., Biague, A., Bamba, S., Kwok, S., Christopherson, C., Biberfeld, G., Albert, J.
(2000). Plasma Viral Load in HIV-1 and HIV-2 Singly and Dually Infected Individuals in Guinea-Bissau, West Africa: Significantly Lower Plasma Virus Set Point in HIV-2 Infection Than in HIV-1 Infection. Arch Intern Med
160: 3286-3293
[Abstract][Full Text]
Lori, F., Lewis, M. G., Xu, J., Varga, G., Zinn Jr., D. E., Crabbs, C., Wagner, W., Greenhouse, J., Silvera, P., Yalley-Ogunro, J., Tinelli, C., Lisziewicz, J.
(2000). Control of SIV Rebound Through Structured Treatment Interruptions During Early Infection. Science
290: 1591-1593
[Abstract][Full Text]
Goldstein, S., Brown, C. R., Dehghani, H., Lifson, J. D., Hirsch, V. M.
(2000). Intrinsic Susceptibility of Rhesus Macaque Peripheral CD4+ T Cells to Simian Immunodeficiency Virus In Vitro Is Predictive of In Vivo Viral Replication. J. Virol.
74: 9388-9395
[Abstract][Full Text]
Quiñones-Mateu, M. E., Ball, S. C., Marozsan, A. J., Torre, V. S., Albright, J. L., Vanham, G., van der Groen, G., Colebunders, R. L., Arts, E. J.
(2000). A Dual Infection/Competition Assay Shows a Correlation between Ex Vivo Human Immunodeficiency Virus Type 1 Fitness and Disease Progression. J. Virol.
74: 9222-9233
[Abstract][Full Text]
Diop, O. M., Gueye, A., Dias-Tavares, M., Kornfeld, C., Faye, A., Ave, P., Huerre, M., Corbet, S., Barre-Sinoussi, F., Müller-Trutwin, M. C.
(2000). High Levels of Viral Replication during Primary Simian Immunodeficiency Virus SIVagm Infection Are Rapidly and Strongly Controlled in African Green Monkeys. J. Virol.
74: 7538-7547
[Abstract][Full Text]
Gea-Banacloche, J. C., Migueles, S. A., Martino, L., Shupert, W. L., McNeil, A. C., Sabbaghian, M. S., Ehler, L., Prussin, C., Stevens, R., Lambert, L., Altman, J., Hallahan, C. W., de Quiros, J. C. L. B., Connors, M.
(2000). Maintenance of Large Numbers of Virus-Specific CD8+ T Cells in HIV-Infected Progressors and Long-Term Nonprogressors. J. Immunol.
165: 1082-1092
[Abstract][Full Text]
Holterman, L., Niphuis, H., Koornstra, W., Dubbes, R., ten Haaft, P., Heeney, J. L.
(2000). The rate of progression to AIDS is independent of virus dose in simian immunodeficiency virus-infected macaques. J. Gen. Virol.
81: 1719-1726
[Abstract][Full Text]
Clementi, M.
(2000). Quantitative Molecular Analysis of Virus Expression and Replication. J. Clin. Microbiol.
38: 2030-2036
[Full Text]
Carpenter, S., Vaughn, E. M., Yang, J., Baccam, P., Roth, J. A., Wannemuehler, Y.
(2000). Antigenic and genetic stability of bovine immunodeficiency virus during long-term persistence in cattle experimentally infected with the BIVR29 isolate. J. Gen. Virol.
81: 1463-1472
[Abstract][Full Text]
Seth, A., Ourmanov, I., Schmitz, J. E., Kuroda, M. J., Lifton, M. A., Nickerson, C. E., Wyatt, L., Carroll, M., Moss, B., Venzon, D., Letvin, N. L., Hirsch, V. M.
(2000). Immunization with a Modified Vaccinia Virus Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol Primes for an Anamnestic Gag-Specific Cytotoxic T-Lymphocyte Response and Is Associated with Reduction of Viremia after SIV Challenge. J. Virol.
74: 2502-2509
[Abstract][Full Text]
Rosenwirth, B., ten Haaft, P., Bogers, W. M. J. M., Nieuwenhuis, I. G., Niphuis, H., Kuhn, E.-M., Bischofberger, N., Heeney, J. L., Überla, K.
(2000). Antiretroviral Therapy during Primary Immunodeficiency Virus Infection Can Induce Persistent Suppression of Virus Load and Protection from Heterologous Challenge in Rhesus Macaques. J. Virol.
74: 1704-1711
[Abstract][Full Text]
de Quiros, J. C. L. B., Shupert, W. L., McNeil, A. C., Gea-Banacloche, J. C., Flanigan, M., Savage, A., Martino, L., Weiskopf, E. E., Imamichi, H., Zhang, Y.-M., Adelsburger, J., Stevens, R., Murphy, P. M., Zimmerman, P. A., Hallahan, C. W., Davey, R. T. Jr., Connors, M.
(2000). Resistance to Replication of Human Immunodeficiency Virus Challenge in SCID-Hu Mice Engrafted with Peripheral Blood Mononuclear Cells of Nonprogressors Is Mediated by CD8+ T Cells and Associated with a Proliferative Response to p24 Antigen. J. Virol.
74: 2023-2028
[Abstract][Full Text]
Spiegel, H. M. L., Ogg, G. S., DeFalcon, E., Sheehy, M. E., Monard, S., Haslett, P. A. J., Gillespie, G., Donahoe, S. M., Pollack, H., Borkowsky, W., McMichael, A. J., Nixon, D. F.
(2000). Human Immunodeficiency Virus Type 1- and Cytomegalovirus-Specific Cytotoxic T Lymphocytes Can Persist at High Frequency for Prolonged Periods in the Absence of Circulating Peripheral CD4+ T Cells. J. Virol.
74: 1018-1022
[Abstract][Full Text]
Preiser, W., Elzinger, B., Brink, N. S
(2000). Quantitative molecular virology in patient management. J. Clin. Pathol.
53: 76-83
[Full Text]
Ogg, G. S., Kostense, S., Klein, M. R., Jurriaans, S., Hamann, D., McMichael, A. J., Miedema, F.
(1999). Longitudinal Phenotypic Analysis of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes: Correlation with Disease Progression. J. Virol.
73: 9153-9160
[Abstract][Full Text]
Gore, S.M., Hutchinson, S.J., Brettle, R.P.
(1999). Study requirements for investigating HLA-associated progression of HIV disease, and review. QJM
92: 609-617
[Full Text]
Hay, C. M., Ruhl, D. J., Basgoz, N. O., Wilson, C. C., Billingsley, J. M., DePasquale, M. P., D'Aquila, R. T., Wolinsky, S. M., Crawford, J. M., Montefiori, D. C., Walker, B. D.
(1999). Lack of Viral Escape and Defective In Vivo Activation of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes in Rapidly Progressive Infection. J. Virol.
73: 5509-5519
[Abstract][Full Text]
Metzner, K. J., Jin, X., Lee, F. V., Gettie, A., Bauer, D. E., Di Mascio, M., Perelson, A. S., Marx, P. A., Ho, D. D., Kostrikis, L. G., Connor, R. I.
(1999). Effects of In Vivo CD8+ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine. J. Exp. Med.
191: 1921-1932
[Abstract][Full Text]
Caselli, E., Betti, M., Grossi, M. P., Balboni, P. G., Rossi, C., Boarini, C., Cafaro, A., Barbanti-Brodano, G., Ensoli, B., Caputo, A.
(1999). DNA Immunization with HIV-1 tat Mutated in the trans Activation Domain Induces Humoral and Cellular Immune Responses Against Wild-Type Tat. J. Immunol.
162: 5631-5638
[Abstract][Full Text]
Wagner, R., Leschonsky, B., Harrer, E., Paulus, C., Weber, C., Walker, B. D., Buchbinder, S., Wolf, H., Kalden, J. R., Harrer, T.
(1999). Molecular and Functional Analysis of a Conserved CTL Epitope in HIV-1 p24 Recognized from a Long-Term Nonprogressor: Constraints on Immune Escape Associated with Targeting a Sequence Essential for Viral Replication. J. Immunol.
162: 3727-3734
[Abstract][Full Text]
Kaur, A., Grant, R. M., Means, R. E., McClure, H., Feinberg, M., Johnson, R. P.
(1998). Diverse Host Responses and Outcomes following Simian Immunodeficiency Virus SIVmac239 Infection in Sooty Mangabeys and Rhesus Macaques. J. Virol.
72: 9597-9611
[Abstract][Full Text]
Stamatos, N. M., Mascola, J. R., Kalyanaraman, V. S., Louder, M. K., Frampton, L. M., Birx, D. L., VanCott, T. C.
(1998). Neutralizing Antibodies from the Sera of Human Immunodeficiency Virus Type 1-Infected Individuals Bind to Monomeric gp120 and Oligomeric gp140. J. Virol.
72: 9656-9667
[Abstract][Full Text]
Spenlehauer, C., Saragosti, S., Fleury, H. J. A., Kirn, A., Aubertin, A.-M., Moog, C.
(1998). Study of the V3 Loop as a Target Epitope for Antibodies Involved in the Neutralization of Primary Isolates versus T-Cell-Line-Adapted Strains of Human Immunodeficiency Virus Type 1. J. Virol.
72: 9855-9864
[Abstract][Full Text]
McChesney, M. B., Collins, J. R., Lu, D., Lu, X., Torten, J., Ashley, R. L., Cloyd, M. W., Miller, C. J.
(1998). Occult Systemic Infection and Persistent Simian Immunodeficiency Virus (SIV)-Specific CD4+-T-Cell Proliferative Responses in Rhesus Macaques That Were Transiently Viremic after Intravaginal Inoculation of SIV. J. Virol.
72: 10029-10035
[Abstract][Full Text]
Grovit-Ferbas, K., Ferbas, J., Gudeman, V., Sadeghi, S., Goetz, M. B., Giorgi, J. V., Chen, I. S. Y., O'Brien, W. A.
(1998). Potential Contributions of Viral Envelope and Host Genetic Factors in a Human Immunodeficiency Virus Type 1-Infected Long-Term Survivor. J. Virol.
72: 8650-8658
[Abstract][Full Text]
Zhang, L., He, T., Huang, Y., Chen, Z., Guo, Y., Wu, S., Kunstman, K. J., Brown, R. C., Phair, J. P., Neumann, A. U., Ho, D. D., Wolinsky, S. M.
(1998). Chemokine Coreceptor Usage by Diverse Primary Isolates of Human Immunodeficiency Virus Type 1. J. Virol.
72: 9307-9312
[Abstract][Full Text]
Barker, E., Mackewicz, C. E., Reyes-Teran, G., Sato, A., Stranford, S. A., Fujimura, S. H., Christopherson, C., Chang, S.-Y., Levy, J. A.
(1998). Virological and Immunological Features of Long-Term Human Immunodeficiency Virus-Infected Individuals Who Have Remained Asymptomatic Compared With Those Who Have Progressed to Acquired Immunodeficiency Syndrome. Blood
92: 3105-3114
[Abstract][Full Text]
Cole, K. S., Murphey-Corb, M., Narayan, O., Joag, S. V., Shaw, G. M., Montelaro, R. C.
(1998). Common Themes of Antibody Maturation to Simian Immunodeficiency Virus, Simian-Human Immunodeficiency Virus, and Human Immunodeficiency Virus Type 1 Infections. J. Virol.
72: 7852-7859
[Abstract][Full Text]
Grassly, N. C., Xiang, Z., Ariyoshi, K., Aaby, P., Jensen, H., Schim van der Loeff, M., Dias, F., Whittle, H., Breuer, J.
(1998). Mortality among Human Immunodeficiency Virus Type 2-Positive Villagers in Rural Guinea-Bissau Is Correlated with Viral Genotype. J. Virol.
72: 7895-7899
[Abstract][Full Text]
Broström, C., Sönnerborg, A., Lindbäck, S., Gaines, H.
(1998). Low Relative Frequencies of CD26+ CD4+ Cells in Long-Term Nonprogressing Human Immunodeficiency Virus Type 1-Infected Subjects. CVI
5: 662-666
[Abstract][Full Text]
Oaks, J. L., McGuire, T. C., Ulibarri, C., Crawford, T. B.
(1998). Equine Infectious Anemia Virus Is Found in Tissue Macrophages during Subclinical Infection. J. Virol.
72: 7263-7269
[Abstract][Full Text]
