FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 340:1715-1722 June 3, 1999 Number 22 Next

	Full Text PDF Editorial by Collins, K. L. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background and Methods The Sydney Blood Bank Cohort consists of a blood donor and eight transfusion recipients who were infected before 1985 with a strain of human immunodeficiency virus type 1 (HIV-1) with a deletion in the region in which the nef gene and the long terminal repeat overlap. Two recipients have died since 1994, at 77 and 83 years of age, of causes unrelated to HIV infection; one other recipient, who had systemic lupus erythematosus, died in 1987 at 22 years of age of causes possibly related to HIV. We present longitudinal immunologic and virologic data on the six surviving members and one deceased member of this cohort through September 30, 1998.

Results The five surviving recipients remain asymptomatic 14 to 18 years after HIV-1 infection without any antiretroviral therapy; however, the donor commenced therapy in February 1999. In three recipients plasma concentrations of HIV-1 RNA are undetectable (<200 copies per milliliter), and in two of these three the CD4 lymphocyte counts have declined by 9 and 30 cells per cubic millimeter per year (P=0.3 and P=0.5, respectively). The donor and two other recipients have median plasma concentrations of HIV-1 RNA of 645 to 2850 copies per milliliter; the concentration has increased in the donor (P<0.001). The CD4 lymphocyte counts in these three cohort members have declined by 16 to 73 cells per cubic millimeter per year (P<0.001). In the recipient who died after 12 years of infection, the median plasma concentration of HIV-1 RNA was 1400 copies per milliliter, with a decline in CD4 lymphocyte counts of 17 cells per cubic millimeter per year (P=0.2).

Conclusions After prolonged infection with this attenuated strain of HIV-1, there is evidence of immunologic damage in three of the four subjects with detectable plasma HIV-1 RNA. The CD4 lymphocyte counts appear to be stable in the three subjects in whom plasma HIV-1 RNA remains undetectable.

Source Information

From the Australian Red Cross Blood Service–New South Wales, Sydney (J.C.L., A.F.G., C.H.R.-G., W.B.D., L.M., J.S.S.); the National Centre in HIV Virology Research and the Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria (J.M., R.B.O., D.I.R., N.J.D.); the National Centre in HIV Epidemiology and Clinical Research, Sydney (L.J.A.); and the Royal Prince Alfred Hospital, Sydney (R.J.G.) — all in Australia. Other authors were Dale A. McPhee, Ph.D., Suzanne Crowe, M.B., B.S., Ajantha E. Solomon, B.Sc., Catherine Chatfield, B.Sc., and Ian R.C. Cooke, Ph.D., National Centre in HIV Virology Research and the Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria; and Sean Blasdall, M.App.Sc., and Harmjan Kuipers, M.Sc., Australian Red Cross Blood Service–New South Wales, Sydney.

Address reprint requests to Ms. Learmont at the Australian Red Cross Blood Service–NSW, 153 Clarence St., Sydney, NSW 2000, Australia, or at jlearmont{at}arcbs.redcross.org.au.

Full Text of this Article

This article has been cited by other articles:

• Ibeh, B. O, Obidoa, O., Uzoegwu, P. N (2008). High plasma activity of endogenous antioxidants protect CD4+ T-cells in HIV-serodiscordant heterosexual partners in a Nigerian population. Int J STD AIDS 19: 536-540 [Abstract] [Full Text]  
• Rollman, E., Smith, M. Z., Brooks, A. G., Purcell, D. F. J., Zuber, B., Ramshaw, I. A., Kent, S. J. (2007). Killing Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells: Implications for HIV Vaccine Strategies. J. Immunol. 179: 4571-4579 [Abstract] [Full Text]  
• Verity, E. E., Zotos, D., Wilson, K., Chatfield, C., Lawson, V. A., Dwyer, D. E., Cunningham, A., Learmont, J., Dyer, W., Sullivan, J., Churchill, M., Wesselingh, S. L., Gabuzda, D., Gorry, P. R., McPhee, D. A. (2007). Viral Phenotypes and Antibody Responses in Long-Term Survivors Infected with Attenuated Human Immunodeficiency Virus Type 1 Containing Deletions in the nef and Long Terminal Repeat Regions. J. Virol. 81: 9268-9278 [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]  
• Friedrich, T. C., Valentine, L. E., Yant, L. J., Rakasz, E. G., Piaskowski, S. M., Furlott, J. R., Weisgrau, K. L., Burwitz, B., May, G. E., Leon, E. J., Soma, T., Napoe, G., Capuano, S. V. III, Wilson, N. A., Watkins, D. I. (2007). Subdominant CD8+ T-Cell Responses Are Involved in Durable Control of AIDS Virus Replication. J. Virol. 81: 3465-3476 [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]  
• Hamano, T., Matsuo, K., Hibi, Y., Victoriano, A. F. B., Takahashi, N., Mabuchi, Y., Soji, T., Irie, S., Sawanpanyalert, P., Yanai, H., Hara, T., Yamazaki, S., Yamamoto, N., Okamoto, T. (2007). A Single-Nucleotide Synonymous Mutation in the gag Gene Controlling Human Immunodeficiency Virus Type 1 Virion Production. J. Virol. 81: 1528-1533 [Abstract] [Full Text]  
• Calugi, G., Montella, F., Favalli, C., Benedetto, A. (2006). Entire Genome of a Strain of Human Immunodeficiency Virus Type 1 with a Deletion of nef That Was Recovered 20 Years after Primary Infection: Large Pool of Proviruses with Deletions of env. J. Virol. 80: 11892-11896 [Abstract] [Full Text]  
• Trible, R. P., Emert-Sedlak, L., Smithgall, T. E. (2006). HIV-1 Nef Selectively Activates Src Family Kinases Hck, Lyn, and c-Src through Direct SH3 Domain Interaction. J. Biol. Chem. 281: 27029-27038 [Abstract] [Full Text]  
• Roeth, J. F., Collins, K. L. (2006). Human Immunodeficiency Virus Type 1 Nef: Adapting to Intracellular Trafficking Pathways. Microbiol. Mol. Biol. Rev. 70: 548-563 [Abstract] [Full Text]  
• Churchill, M. J., Rhodes, D. I., Learmont, J. C., Sullivan, J. S., Wesselingh, S. L., Cooke, I. R. C., Deacon, N. J., Gorry, P. R. (2006). Longitudinal Analysis of Human Immunodeficiency Virus Type 1 nef/Long Terminal Repeat Sequences in a Cohort of Long-Term Survivors Infected from a Single Source. J. Virol. 80: 1047-1052 [Abstract] [Full Text]  
• Raney, A., Kuo, L. S., Baugh, L. L., Foster, J. L., Garcia, J. V. (2005). Reconstitution and Molecular Analysis of an Active Human Immunodeficiency Virus Type 1 Nef/p21-Activated Kinase 2 Complex. J. Virol. 79: 12732-12741 [Abstract] [Full Text]  
• Chaudhry, A., Das, S. R., Hussain, A., Mayor, S., George, A., Bal, V., Jameel, S., Rath, S. (2005). The Nef Protein of HIV-1 Induces Loss of Cell Surface Costimulatory Molecules CD80 and CD86 in APCs. J. Immunol. 175: 4566-4574 [Abstract] [Full Text]  
• Brown, A., Gartner, S., Kawano, T., Benoit, N., Cheng-Mayer, C. (2005). HLA-A2 down-regulation on primary human macrophages infected with an M-tropic EGFP-tagged HIV-1 reporter virus. J. Leukoc. Biol. 78: 675-685 [Abstract] [Full Text]  
• Omoto, S., Fujii, Y. R. (2005). Regulation of human immunodeficiency virus 1 transcription by nef microRNA. J. Gen. Virol. 86: 751-755 [Abstract] [Full Text]  
• Choi, J., Walker, J., Boichuk, S., Kirkiles-Smith, N., Torpey, N., Pober, J. S., Alexander, L. (2005). Human Endothelial Cells Enhance Human Immunodeficiency Virus Type 1 Replication in CD4+ T Cells in a Nef-Dependent Manner In Vitro and In Vivo. J. Virol. 79: 264-276 [Abstract] [Full Text]  
• Swigut, T., Alexander, L., Morgan, J., Lifson, J., Mansfield, K. G., Lang, S., Johnson, R. P., Skowronski, J., Desrosiers, R. (2004). Impact of Nef-Mediated Downregulation of Major Histocompatibility Complex Class I on Immune Response to Simian Immunodeficiency Virus. J. Virol. 78: 13335-13344 [Abstract] [Full Text]  
• Jin, Y.-J., Zhang, X., Boursiquot, J. G., Burakoff, S. J. (2004). CD4 Phosphorylation Partially Reverses Nef Down-Regulation of CD4. J. Immunol. 173: 5495-5500 [Abstract] [Full Text]  
• Brown, A., Moghaddam, S., Kawano, T., Cheng-Mayer, C. (2004). Multiple human immunodeficiency virus type 1 Nef functions contribute to efficient replication in primary human macrophages. J. Gen. Virol. 85: 1463-1469 [Abstract] [Full Text]  
• Giri, M., Ugen, K. E., Weiner, D. B. (2004). DNA Vaccines against Human Immunodeficiency Virus Type 1 in the Past Decade. Clin. Microbiol. Rev. 17: 370-389 [Abstract] [Full Text]  
• Geels, M. J., Cornelissen, M., Schuitemaker, H., Anderson, K., Kwa, D., Maas, J., Dekker, J. T., Baan, E., Zorgdrager, F., van den Burg, R., van Beelen, M., Lukashov, V. V., Fu, T.-M., Paxton, W. A., van der Hoek, L., Dubey, S. A., Shiver, J. W., Goudsmit, J. (2003). Identification of Sequential Viral Escape Mutants Associated with Altered T-Cell Responses in a Human Immunodeficiency Virus Type 1-Infected Individual. J. Virol. 77: 12430-12440 [Abstract] [Full Text]  
• Fine, P. E. M. (2003). The Interval between Successive Cases of an Infectious Disease. Am J Epidemiol 158: 1039-1047 [Abstract] [Full Text]  
• Schindler, M., Wurfl, S., Benaroch, P., Greenough, T. C., Daniels, R., Easterbrook, P., Brenner, M., Munch, J., Kirchhoff, F. (2003). Down-Modulation of Mature Major Histocompatibility Complex Class II and Up-Regulation of Invariant Chain Cell Surface Expression Are Well-Conserved Functions of Human and Simian Immunodeficiency Virus nef Alleles. J. Virol. 77: 10548-10556 [Abstract] [Full Text]  
• Arganaraz, E. R., Schindler, M., Kirchhoff, F., Cortes, M. J., Lama, J. (2003). Enhanced CD4 Down-modulation by Late Stage HIV-1 nef Alleles Is Associated with Increased Env Incorporation and Viral Replication. J. Biol. Chem. 278: 33912-33919 [Abstract] [Full Text]  
• Padua, E., Jenkins, A., Brown, S., Bootman, J., Paixao, M. T., Almond, N., Berry, N. (2003). Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal. J. Gen. Virol. 84: 1287-1299 [Abstract] [Full Text]  
• Stoddart, C. A., Geleziunas, R., Ferrell, S., Linquist-Stepps, V., Moreno, M. E., Bare, C., Xu, W., Yonemoto, W., Bresnahan, P. A., McCune, J. M., Greene, W. C. (2003). Human Immunodeficiency Virus Type 1 Nef-Mediated Downregulation of CD4 Correlates with Nef Enhancement of Viral Pathogenesis. J. Virol. 77: 2124-2133 [Abstract] [Full Text]  
• Voss, G., Manson, K., Montefiori, D., Watkins, D. I., Heeney, J., Wyand, M., Cohen, J., Bruck, C. (2002). Prevention of Disease Induced by a Partially Heterologous AIDS Virus in Rhesus Monkeys by Using an Adjuvanted Multicomponent Protein Vaccine. J. Virol. 77: 1049-1058 [Abstract] [Full Text]  
• Chakrabarti, L. A., Metzner, K. J., Ivanovic, T., Cheng, H., Louis-Virelizier, J., Connor, R. I., Cheng-Mayer, C. (2002). A Truncated Form of Nef Selected during Pathogenic Reversion of Simian Immunodeficiency Virus SIVmac239{Delta}nef Increases Viral Replication. J. Virol. 77: 1245-1256 [Abstract] [Full Text]  
• Barbour, J. D., Wrin, T., Grant, R. M., Martin, J. N., Segal, M. R., Petropoulos, C. J., Deeks, S. G. (2002). Evolution of Phenotypic Drug Susceptibility and Viral Replication Capacity during Long-Term Virologic Failure of Protease Inhibitor Therapy in Human Immunodeficiency Virus-Infected Adults. J. Virol. 76: 11104-11112 [Abstract] [Full Text]  
• Alexander, L., Aquino-DeJesus, M. J., Chan, M., Andiman, W. A. (2002). Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Replication by a Two-Amino-Acid Insertion in HIV-1 Vif from a Nonprogressing Mother and Child. J. Virol. 76: 10533-10539 [Abstract] [Full Text]  
• Ignatius, R., Tenner-Racz, K., Messmer, D., Gettie, A., Blanchard, J., Luckay, A., Russo, C., Smith, S., Marx, P. A., Steinman, R. M., Racz, P., Pope, M. (2002). Increased Macrophage Infection upon Subcutaneous Inoculation of Rhesus Macaques with Simian Immunodeficiency Virus-Loaded Dendritic Cells or T Cells but Not with Cell-Free Virus. J. Virol. 76: 9787-9797 [Abstract] [Full Text]  
• Jekle, A., Schramm, B., Jayakumar, P., Trautner, V., Schols, D., De Clercq, E., Mills, J., Crowe, S. M., Goldsmith, M. A. (2002). Coreceptor Phenotype of Natural Human Immunodeficiency Virus with Nef Deleted Evolves In Vivo, Leading to Increased Virulence. J. Virol. 76: 6966-6973 [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]  
• Nilsson, C., Sutter, G., Walther-Jallow, L., ten Haaft, P., Akerblom, L., Heeney, J., Erfle, V., Bottiger, P., Biberfeld, G., Thorstensson, R. (2002). Immunization with recombinant modified vaccinia virus Ankara can modify mucosal simian immunodeficiency virus infection and delay disease progression in macaques. J. Gen. Virol. 83: 807-818 [Abstract] [Full Text]  
• Kent, S. J., Dale, C. J., Preiss, S., Mills, J., Campagna, D., Purcell, D. F. J. (2001). Vaccination with Attenuated Simian Immunodeficiency Virus by DNA Inoculation. J. Virol. 75: 11930-11934 [Abstract] [Full Text]  
• Hanke, T (2001). Prospect of a prophylactic vaccine for HIV. Br Med Bull 58: 205-218 [Abstract] [Full Text]  
• Barouch, D. H., Santra, S., Kuroda, M. J., Schmitz, J. E., Plishka, R., Buckler-White, A., Gaitan, A. E., Zin, R., Nam, J.-H., Wyatt, L. S., Lifton, M. A., Nickerson, C. E., Moss, B., Montefiori, D. C., Hirsch, V. M., Letvin, N. L. (2001). Reduction of Simian-Human Immunodeficiency Virus 89.6P Viremia in Rhesus Monkeys by Recombinant Modified Vaccinia Virus Ankara Vaccination. J. Virol. 75: 5151-5158 [Abstract] [Full Text]  
• Guan, Y., Whitney, J. B., Detorio, M., Wainberg, M. A. (2001). Construction and In Vitro Properties of a Series of Attenuated Simian Immunodeficiency Viruses with All Accessory Genes Deleted. J. Virol. 75: 4056-4067 [Abstract] [Full Text]  
• Blower, S. M., Koelle, K., Kirschner, D. E., Mills, J. (2001). Live attenuated HIV vaccines: Predicting the tradeoff between efficacy and safety. Proc. Natl. Acad. Sci. USA 98: 3618-3623 [Abstract] [Full Text]  
• Fultz, P. N., Vance, P. J., Endres, M. J., Tao, B., Dvorin, J. D., Davis, I. C., Lifson, J. D., Montefiori, D. C., Marsh, M., Malim, M. H., Hoxie, J. A. (2001). In Vivo Attenuation of Simian Immunodeficiency Virus by Disruption of a Tyrosine-Dependent Sorting Signal in the Envelope Glycoprotein Cytoplasmic Tail. J. Virol. 75: 278-291 [Abstract] [Full Text]  
• Rhodes, D. I., Ashton, L., Solomon, A., Carr, A., Cooper, D., Kaldor, J., Deacon, N. (2000). Characterization of Three nef-Defective Human Immunodeficiency Virus Type 1 Strains Associated with Long-Term Nonprogression. J. Virol. 74: 10581-10588 [Abstract] [Full Text]  
• Dejucq, N. (2000). HIV-1 replication in CD4+ T cell lines: the effects of adaptation on co-receptor use, tropism, and accessory gene function. J. Leukoc. Biol. 68: 331-337 [Abstract] [Full Text]  
• Alexander, L., Weiskopf, E., Greenough, T. C., Gaddis, N. C., Auerbach, M. R., Malim, M. H., O'Brien, S. J., Walker, B. D., Sullivan, J. L., Desrosiers, R. C. (2000). Unusual Polymorphisms in Human Immunodeficiency Virus Type 1 Associated with Nonprogressive Infection. J. Virol. 74: 4361-4376 [Abstract] [Full Text]  
• Camerini, D., Su, H.-P., Gamez-Torre, G., Johnson, M. L., Zack, J. A., Chen, I. S. Y. (2000). Human Immunodeficiency Virus Type 1 Pathogenesis in SCID-hu Mice Correlates with Syncytium-Inducing Phenotype and Viral Replication. J. Virol. 74: 3196-3204 [Abstract] [Full Text]  
• Pinching, A. J (2000). Live attenuated vaccine trials in medically informed volunteers: a special case?. J. Med. Ethics 26: 44-46 [Abstract] [Full Text]  
• Brown, A., Wang, X., Sawai, E., Cheng-Mayer, C. (1999). Activation of the PAK-Related Kinase by Human Immunodeficiency Virus Type 1 Nef in Primary Human Peripheral Blood Lymphocytes and Macrophages Leads to Phosphorylation of a PIX-p95 Complex. J. Virol. 73: 9899-9907 [Abstract] [Full Text]  
• Verhasselt, B., Naessens, E., Verhofstede, C., De Smedt, M., Schollen, S., Kerre, T., Vanhecke, D., Plum, J. (1999). Human Immunodeficiency Virus nef Gene Expression Affects Generation and Function of Human T Cells, But Not Dendritic Cells. Blood 94: 2809-2818 [Abstract] [Full Text]  
• (1999). Attenuated HIV Strain Causes Immune Deterioration. JWatch Infect. Diseases 1999: 11-11 [Full Text]  
• Collins, K. L., Nabel, G. J. (1999). Naturally Attenuated HIV -- Lessons for AIDS Vaccines and Treatment. NEJM 340: 1756-1757 [Full Text]  
• Smith, S. M., Khoroshev, M., Marx, P. A., Orenstein, J., Jeang, K.-T. (2001). Constitutively Dead, Conditionally Live HIV-1 Genomes. EX VIVO IMPLICATIONS FOR A LIVE VIRUS VACCINE. J. Biol. Chem. 276: 32184-32190 [Abstract] [Full Text]  
• Marzio, G., Verhoef, K., Vink, M., Berkhout, B. (2001). In vitro evolution of a highly replicating, doxycycline-dependent HIV for applications in vaccine studies. Proc. Natl. Acad. Sci. USA 98: 6342-6347 [Abstract] [Full Text]