1887

Abstract

Within human immunodeficiency virus type 1 (HIV-1)-infected patients, there are those who have been infected for more than 10 years with a CD4 cell count of >500 cells μl and who remain asymptomatic without antiretroviral therapy; these patients are designated long-term non-progressors (LTNPs). In a set of 16 LTNPs, viral dating, DNA viral load, quasispecies heterogeneity and antibody (Ab) titres against gp160 and microglobulin ( m) were determined. Plasma viral RNA and CD4 and CD8 T-cell numbers were estimated in more than three samples per patient. Host genetic characteristics, such as Δ32- genotype and human leukocyte antigen (HLA) genotype and supertypes, and clinical–epidemiological factors were evaluated. Dating of global populations and of DNA and RNA viral quasispecies identified two subsets of patients: one displaying only ancestral sequences and the other displaying predominantly modern sequences. The ancestral patients displayed a significant reduction in RNA and DNA viral loads, quasispecies heterogeneity, CD8 cell number, anti-gp160 Ab titres and m level, and they were also associated with better use of safe-sex practices and higher presence of the HLA sB58 supertype than the modern subset. Viral dating has therefore permitted the segregation of LTNPs into two subsets that show very different virological, immunological, host and clinical–epidemiological characteristics. Moreover, whereas the modern subset displayed low levels of virus replication, the ancestral group displayed not only a very limited virus replication, often to undetectable levels, but also very slow or arrested viral evolution, maintaining the close relationship of the viral population to the transmitted virus.

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2005-02-01
2024-04-25
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References

  1. Bacchetti P., Moss A. R. 1989; Incubation period of AIDS in San Francisco. Nature 338:251–253 [CrossRef]
    [Google Scholar]
  2. Balotta C., Bagnarelli P., Riva C. 9 other authors 1997; Comparable biological and molecular determinants in HIV type 1-infected long-term nonprogressors and recently infected individuals. AIDS Res Hum Retrovir 13:337–341 [CrossRef]
    [Google Scholar]
  3. Barker E., Mackewicz C. E., Reyes-Terán 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
    [Google Scholar]
  4. Bello G., Casado C., García S., Rodríguez C., del Romero J., López-Galíndez C. 2004; Co-existence of recent and ancestral nucleotide sequences in viral quasispecies of human immunodeficiency virus type 1 patients. J Gen Virol 85:399–407 [CrossRef]
    [Google Scholar]
  5. Boom R., Sol C. J. A., Salimans M. M. M., Jansen C. L., Wertheim-van Dillen P. M. E., van der Noordaa J. 1990; Rapid and simple method for purification of nucleic acids. J Clin Microbiol 28:495–503
    [Google Scholar]
  6. Buchbinder S. P., Katz M. H., Hessol N. A., O'Malley P. M., Holmberg S. D. 1994; Long-term HIV-1 infection without immunologic progression. AIDS 8:1123–1128 [CrossRef]
    [Google Scholar]
  7. Cao Y., Qin L., Zhang L., Safrit J., Ho D. D. 1995; Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med 332:201–208 [CrossRef]
    [Google Scholar]
  8. Carotenuto P., Looij D., Keldermans L., de Wolf F., Goudsmit J. 1998; Neutralizing antibodies are positively associated with CD4+ T-cell counts and T-cell function in long-term AIDS-free infection. AIDS 12:1591–1600 [CrossRef]
    [Google Scholar]
  9. Casado C., Urtasun I., Martin-Walther M. V., Garcia S., Rodriguez C., del Romero J., Lopez-Galindez C. 2000; Genetic analysis of HIV-1 samples from Spain. J Acquir Immune Defic Syndr 23:68–74 [CrossRef]
    [Google Scholar]
  10. Casado C., García S., Rodríguez C., del Romero J., Bello G., López-Galíndez C. 2001; Different evolutionary patterns are found within human immunodeficiency virus type 1-infected patients. J Gen Virol 82:2495–2508
    [Google Scholar]
  11. Dean M., Carrington M., Winkler C. 14 other authors 1996; Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 273:1856–1862 [CrossRef]
    [Google Scholar]
  12. Fauci A. S. 1996; Host factors and the pathogenesis of HIV-induced disease. Nature 384:529–534 [CrossRef]
    [Google Scholar]
  13. Ferbas J., Kaplan A. H., Hausner M. A. 7 other authors 1995; Virus burden in long-term survivors of human immunodeficiency virus (HIV) infection is a determinant of anti-HIV CD8+ lymphocyte activity. J Infect Dis 172:329–339 [CrossRef]
    [Google Scholar]
  14. Finzi D., Siliciano R. F. 1998; Viral dynamics in HIV-1 infection. Cell 93:665–671 [CrossRef]
    [Google Scholar]
  15. Harrer T., Harrer E., Kalams S. A. 10 other authors 1996; Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection. AIDS Res Hum Retrovir 12:585–592 [CrossRef]
    [Google Scholar]
  16. Hendriks J. C., Medley G. F., van Griensven G. J., Coutinho R. A., Heisterkamp S. H., van Druten H. A. 1993; The treatment-free incubation period of AIDS in a cohort of homosexual men. AIDS 7:231–239 [CrossRef]
    [Google Scholar]
  17. Hogan C. M., Hammer S. M. 2001; Host determinants in HIV infection and disease. Part 2: genetic factors and implications for antiretroviral therapeutics. Ann Intern Med 134:978–996 [CrossRef]
    [Google Scholar]
  18. Hogervorst E., Jurriaans S., de Wolf F. 8 other authors 1995; Predictors for non- and slow progression in human immunodeficiency virus (HIV) type 1 infection: low viral RNA copy numbers in serum and maintenance of high HIV-1 p24-specific but not V3-specific antibody levels. J Infect Dis 171:811–821 [CrossRef]
    [Google Scholar]
  19. Keet I. P., Krol A., Klein M. R. 7 other authors 1994; Characteristics of long-term asymptomatic infection with human immunodeficiency virus type 1 in men with normal and low CD4+ cell counts. J Infect Dis 169:1236–1243 [CrossRef]
    [Google Scholar]
  20. Klein M. R., van Baalen C. A., Holwerda A. M. 7 other authors 1995; Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics. J Exp Med 181:1365–1372 [CrossRef]
    [Google Scholar]
  21. Korber B., Muldoon M., Theiler J., Gao F., Gupta R., Lapedes A., Hahn B. H., Wolinsky S., Bhattacharya T. 2000; Timing the ancestor of the HIV-1 pandemic strains. Science 288:1789–1796 [CrossRef]
    [Google Scholar]
  22. Kumar S., Tamura K., Jakobsen I. B., Nei M. 2001; mega2: molecular evolutionary genetic analysis software. Bioinformatics 17:1244–1245 [CrossRef]
    [Google Scholar]
  23. Learmont J., Tindall B., Evans L., Cunningham A., Cunningham P., Wells J., Penny R., Kaldor J., Cooper D. A. 1992; Long-term symptomless HIV-1 infection in recipients of blood products from a single donor. Lancet 340:863–867 [CrossRef]
    [Google Scholar]
  24. Lefrère J.-J., Morand-Joubert L., Mariotti M., Bludau H., Burghoffer B., Petit J.-C., Roudot-Thoraval F. 1997; Even individuals considered as long-term nonprogressors show biological signs of progression after 10 years of human immunodeficiency virus infection. Blood 90:1133–1140
    [Google Scholar]
  25. Leitner T., Albert J. 1999; The molecular clock of HIV-1 unveiled through analysis of a known transmission history. Proc Natl Acad Sci U S A 96:10752–10757 [CrossRef]
    [Google Scholar]
  26. Lemey P., Pybus O. G., Wang B., Saksena N. K., Salemi M., Vandamme A.-M. 2003; Tracing the origin and history of the HIV-2 epidemic. Proc Natl Acad Sci U S A 100:6588–6592 [CrossRef]
    [Google Scholar]
  27. Levy J. A. 1993; HIV pathogenesis and long-term survival. AIDS 7:1401–1410 [CrossRef]
    [Google Scholar]
  28. Lifson A. R., Buchbinder S. P., Sheppard H. W., Mawle A. C., Wilber J. C., Stanley M., Hart C. E., Hessol N. A., Holmberg S. D. 1991; Long-term human immunodeficiency virus infection in asymptomatic homosexual and bisexual men with normal CD4+ lymphocyte counts: immunologic and virologic characteristics. J Infect Dis 163:959–965 [CrossRef]
    [Google Scholar]
  29. Lukashov V. V., Goudsmit J. 2002; Recent evolutionary history of human immunodeficiency virus type 1 subtype B: reconstruction of epidemic onset based on sequence distances to the common ancestor. J Mol Evol 54:680–691 [CrossRef]
    [Google Scholar]
  30. Mani I., Gilbert P., Sankalé J.-L., Eisen G., Mboup S., Kanki P. J. 2002; Intrapatient diversity and its correlation with viral setpoint in human immunodeficiency virus type 1 CRF02_A/G-IbNG infection. J Virol 76:10745–10755 [CrossRef]
    [Google Scholar]
  31. Markham R. B., Wang W.-C., Weisstein A. E. 8 other authors 1998; Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline. Proc Natl Acad Sci U S A 95:12568–12573 [CrossRef]
    [Google Scholar]
  32. Menzo S., Sampaolesi R., Vicenzi E. 7 other authors 1998; Rare mutations in a domain crucial for V3-loop structure prevail in replicating HIV from long-term non-progressors. AIDS 12:985–997 [CrossRef]
    [Google Scholar]
  33. Michael N. L., Chang G., Louie L. G., Mascola J. R., Dondero D., Birx D. L., Sheppard H. W. 1997; The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression. Nat Med 3:338–340 [CrossRef]
    [Google Scholar]
  34. Montefiori D. C., Pantaleo G., Fink L. M., Zhou J. T., Zhou J. Y., Bilska M., Miralles G. D., Fauci A. S. 1996; Neutralizing and infection-enhancing antibody responses to human immunodeficiency virus type 1 in long-term nonprogressors. J Infect Dis 173:60–67 [CrossRef]
    [Google Scholar]
  35. Muñoz A., Wang M.-C., Bass S., Taylor J. M. G., Kingsley L. A., Chmiel J. S., Polk B. F. 1989; Acquired immunodeficiency syndrome (AIDS)-free time after human immunodeficiency virus type 1 (HIV-1) seroconversion in homosexual men. Am J Epidemiol 130:530–539
    [Google Scholar]
  36. Pantaleo G., Menzo S., Vaccarezza M. 11 other authors 1995; Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Engl J Med 332:209–216 [CrossRef]
    [Google Scholar]
  37. Pilgrim A. K., Pantaleo G., Cohen O. J., Fink L. M., Zhou J. Y., Zhou J. T., Bolognesi D. P., Fauci A. S., Montefiori D. C. 1997; Neutralizing antibody responses to human immunodeficiency virus type 1 in primary infection and long-term-nonprogressive infection. J Infect Dis 176:924–932 [CrossRef]
    [Google Scholar]
  38. Rinaldo C., Huang X.-L., Fan Z. 8 other authors 1995; High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors. J Virol 69:5838–5842
    [Google Scholar]
  39. Robbins K. E., Lemey P., Pybus O. G., Jaffe H. W., Youngpairoj A. S., Brown T. M., Salemi M., Vandamme A. M., Kalish M. L. 2003; U.S. human immunodeficiency virus type 1 epidemic: date of origin, population history, and characterization of early strains. J Virol 77:6359–6366 [CrossRef]
    [Google Scholar]
  40. Rodrigo A. G., Goracke P. C., Rowhanian K., Mullins J. I. 1997; Quantitation of target molecules from polymerase chain reaction-based limiting dilution assays. AIDS Res Hum Retrovir 13:737–742 [CrossRef]
    [Google Scholar]
  41. Sette A., Sidney J. 1999; Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism. Immunogenetics 50:201–212 [CrossRef]
    [Google Scholar]
  42. Sheppard H. W., Lang W., Ascher M. S., Vittinghoff E., Winkelstein W. 1993; The characterization of non-progressors: long-term HIV-1 infection with stable CD4+ T-cell levels. AIDS 7:1159–1166 [CrossRef]
    [Google Scholar]
  43. Thompson J. D., Higgins D. G., Gibson T. J. 1994; clustal w: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680 [CrossRef]
    [Google Scholar]
  44. Trachtenberg E., Korber B., Sollars C. 12 other authors 2003; Advantage of rare HLA supertype in HIV disease progression. Nat Med 9:928–935 [CrossRef]
    [Google Scholar]
  45. Visco-Comandini U., Aleman S., Yun Z., Sonnerborg A. 2001; Human immunodeficiency virus type 1 variability and long-term non-progression. J Biol Regul Homeost Agents 15:299–303
    [Google Scholar]
  46. Wang B., Mikhail M., Dyer W. B., Zaunders J. J., Kelleher A. D., Saksena N. K. 2003; First demonstration of a lack of viral sequence evolution in a nonprogressor, defining replication-incompetent HIV-1 infection. Virology 312:135–150 [CrossRef]
    [Google Scholar]
  47. Zhang Y. J., Fracasso C., Fiore J. R., Bjorndal A., Angarano G., Gringeri A., Fenyo E. M. 1997; Augmented serum neutralizing activity against primary human immunodeficiency virus type 1 (HIV-1) isolates in two groups of HIV-1-infected long-term nonprogressors. J Infect Dis 176:1180–1187 [CrossRef]
    [Google Scholar]
  48. Zhu T., Korber B. T., Nahmias A. J., Hooper E., Sharp P. M., Ho D. D. 1998; An African HIV-1 sequence from 1959 and implications for the origin of the epidemic. Nature 391:594–597 [CrossRef]
    [Google Scholar]
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