Advertisement

Transient or occult HIV infections may occur more frequently than progressive infections: changing the paradigm about HIV persistence

  • G. K. Sahu
  • T. McNearney
  • A. Evans
  • A. Turner
  • S. Weaver
  • J. C. Huang
  • S. Baron
  • D. Paar
  • M. W. Cloyd
Conference paper

Summary

Evidence of transient HIV infections was found in 8 subjects at high-risk for HIV infection among 47 longitudinally studied over 2–5 (average ∼3.5) years, whereas only two subjects developed progressive infection. All of these subjects developed serum antibodies (Ab) to conformational epitopes of HIV gp41 (termed “early HIV Ab”), but the 8 transiently infected subjects lost this Ab within 4–18 months, and did not seroconvert to positivity in denatured antigen EIA or Western Blot (WB). However, the two progressively infected subjects eventually seroconverted in the EIA and WB tests within one to two months after the appearance of “early HIV Ab”. HIV env and nef sequences were directly PCR amplified from the peripheral blood mononuclear cells (PBMCs) of two of the eight transiently infected subjects during the time of “early HIV Ab”-postivity, and these showed significant sequence divergence from the HIV strains in the laboratory, indicating that they were not laboratory contaminants. Genome identity typing (“paternity-typing”) of PBMC samples obtained at the time of “early HIV Ab”-positivity, and later when Ab was absent from each of the 8 subjects, showed that blood samples were not mixed-up. This provides further evidence that transient or occult infection with HIV does occur, and perhaps at a greater frequency than do progressive infections.

Keywords

Transient Infection Progressive Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Tyler KL, Nathanson N (2001) Pathogenesis of viral infections, chap. 9. Fundamental virology, 4th edn. In: Knipe DM, Howley PM (eds) Lippincott, Williams and Wilkins, N.Y., pp 199–243Google Scholar
  2. 2.
    Hyams KC (1995) Risks of chronicity following acute hepatitis B virus infection: a review. Clin Infect Dis 20: 992–1000PubMedGoogle Scholar
  3. 3.
    Farci P, Alter HJ, Wong D et al (1991) A long term study of hepatitis C virus replication in non-A, non-B hepatitis. N Eng J Med 325: 998–104CrossRefGoogle Scholar
  4. 4.
    Fox JP, Brandt D et al (1969) The virus watch program; a continuing surveillance of viral infections in metropolitan New York. VI observations of adenovirus infections: virus excretion, patterns, antibody response, efficiency of surveillance, pattern of infection are relative to illness. Am J Epidemiol 89: 25–50PubMedGoogle Scholar
  5. 5.
    Ahmad R, Morrison LA, Knipe DM et al (eds) (1997) Viral persistence. In: Viral pathogenesis. Lippincott-Raven, Philadelphia, pp 181–205Google Scholar
  6. 6.
    Whitley RJ, Gnann JW (1993) The epidemiology and clinical manifestation of herpes simplex virus infections. In: Roizman B, Whitely RJ, Lopez C (eds) The human retrovirus. Raven, New York, 29–105Google Scholar
  7. 7.
    Imagawa DT, Lee MH, Wolinsky SM et al (1989) Human immunodeficiency virus type 1 infection in homosexual men who remain seronegative for prolonged periods. N Engl J Med 320: 1458–1462PubMedCrossRefGoogle Scholar
  8. 8.
    Bryson YJ, Pang S, Wei LS et al (1995) Clearance of HIV infection in a perinatally infected infant. N Engl J Med 332: 833–838PubMedCrossRefGoogle Scholar
  9. 9.
    Gorrino MT, Campelo C, Suarez MD et al (1994) Detection of human immunodeficiency virus type 1 by PCR before seroconversion in high-risk individuals who remain seronegative for prolonged periods. Eur J Clin Microbiol Infect Dis 13: 271–276PubMedCrossRefGoogle Scholar
  10. 10.
    Detels R, Mann D, Carrington M et al (1996) Persistently seronegative men from whom HIV-1 has been isolated are genetically and immunologically distinct. Immun Lett 51: 29–33CrossRefGoogle Scholar
  11. 11.
    Tarjan V, Ujhelyi R, Krall G et al (1998) Three cases of transient HIV-1 seropositivity observed in 10 years of practice of a national HIV confirmatory laboratory. AIDS 12: 120–121PubMedGoogle Scholar
  12. 12.
    Farzadegan H, Polis MA, Wolinsky SM et al (1988) Loss of human immunodeficiency virus type 1 (HIV-1) antibodies with evidence of viral infection in asymptomatic homosexual men. Ann Int Med 108: 785–790PubMedGoogle Scholar
  13. 13.
    Burger H, Weiser B, Robinson WS et al (1985) Transient antibody to lymphadenopathy-associated virus/Human T-lymphotropic virus type III and T-lymphocyte abnormalities in the wife of a man who developed the acquired immunodeficiency syndrome. Ann Int Med 103: 545–547PubMedGoogle Scholar
  14. 14.
    Palumbo P, Skurnick J, Lewis D, Eisenberg M (1995) PCR analysis of HIV-seronegative, heterosexual partners of HIV-infected individuals. J Acquir Immune Defic Syndr Human Retrovirol 10: 436–440Google Scholar
  15. 15.
    Roques PA, Gras G, Parnet-Matheiu F, Mabondzo AM, Dollfus C, Narwa R, Marce D, Tranchot-Diallo J, Herve F, Lasfargues GL (1995) Clearance of HIV infection in 12 perinatally infected children: clinical, virological and immunological data. AIDS 9: F19PubMedGoogle Scholar
  16. 16.
    Sahu GK, Chen JY, Huang J et al (2001) Transient or occult HIV-1 infection in high-risk adults. AIDS 15: 1175–1177PubMedCrossRefGoogle Scholar
  17. 17.
    Zhu T, Corey L, Hwangbo Y, Lee JM, Learn GH, Mullins JI, McElrath MJ (2003) Persistence of extraordinarily low levels of genetically homogeneous human immunodeficiency virus type 1 in exposed seronegative individuals. J Virol 77(11): 6108–6116PubMedCrossRefGoogle Scholar
  18. 18.
    Osterholm MD, Hedberg CW, MacDonald KL (1995) Epidemiology infectious disease in principles and practice of infectious diseases. In: Mandell, Douglas, Bennett (eds) 4th edn. Churchill Livingstone Inc., pp 158–168Google Scholar
  19. 19.
    Imagawa D, Detals R (1991) HIV-1 in seronegative homosexual men (letter to the editor). N Eng J Med 325: 1250–1251CrossRefGoogle Scholar
  20. 20.
    Maria AD, Cirillo C, Moretto L (1994) Occurrence of Human Immunodeficiency Virus Type 1 (HIV-1)-specific cytotoxic T cell activity in apparently uninfected children born to HIV-1 infected mothers. J Infect Dis 170: 1296–1299PubMedGoogle Scholar
  21. 21.
    Rowland-Jones S, Nixon FD, Aldhous MC et al (1993) HIV-specific cytotoxic T-cell activity in HIV-exposed but uninfected infants. The Lancet 341: 860–861CrossRefGoogle Scholar
  22. 22.
    Borkowsky W, Krasinski K, Moore T, Papaevangelou V (1990) Lymphocyte proliferative responses to HIV-1 envelope and core antigens by infected and uninfected adults and children. AIDS Res Human Retrovir 6: 673–678Google Scholar
  23. 23.
    Frenkel LM, Mullins JI, Learn GH et al (1998) Genetic evaluation of suspected cases of transient HIV-1 infection of infants. Science 280: 1073–1077PubMedCrossRefGoogle Scholar
  24. 24.
    Shearer GM, Clerici M (1996) Protective immunity against HIV infection: has nature done the experiment for us? Immunol Today 17: 21–24PubMedCrossRefGoogle Scholar
  25. 25.
    Smith MW, Dean M, Carrington M et al (1997) Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Science 277: 959–965PubMedCrossRefGoogle Scholar
  26. 26.
    Detels R, Liu Z, Hennessey K et al (1994) Resistence to HIV-1 infection. JAcquir Immune Defic Syndr 7: 1263–1269Google Scholar
  27. 27.
    Soriano A, Martinez C, Garcia F, Plana M, Palou E, Lejeune M, Arostegui JI, De Lazzari E, Rodriguez C, Barrasa A, Lorenzo JI, Alcami J, del Romero J, Miro JM, Gatell JM, Gallart T (2002) Plasma stromal cell-derived factor (SDF)-1 levels, SDF1-3′A genotype, and expression of CXCR4 on T lymphocytes: their impact on resistance to human immunodeficiency virus type 1 infection and its progression. J Infect Dis 186: 922–931PubMedCrossRefGoogle Scholar
  28. 28.
    Rowland-Jones S, Sutton J, Ariyoshi K et al (1995) HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women. Nat Med 1: 59–64PubMedCrossRefGoogle Scholar
  29. 29.
    Fowke KR, Nagelkerke NJD et al (1996) Resistance to HIV-1 infection among persistently seronegative prostitutes in Naibori, Kenya. Lancet 348: 1347–1351PubMedCrossRefGoogle Scholar
  30. 30.
    Bernard NF, Yannakis CM, Lee JS, Tsoukas CM (1999) Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocyte activity in HIV-exposed seronegative persons. J Infect Dis 179: 538–547PubMedCrossRefGoogle Scholar
  31. 31.
    Rowland-Jones SL, Dong T, Dorrell L, Ogg G, Hansasuta P, Krausa P, Kimani J, Sabally S, Ariyoshi K, Oyugi J, MacDonald KS, Bwayo J, Whittle H, Plummer FA, McMichael AJ (1999) Broadly cross-reactive HIV-specific cytotoxic T-Lymphocytes in highly-exposed persistently seronegative donors. Immunol Lett 66: 9–14PubMedCrossRefGoogle Scholar
  32. 32.
    Kaul R, Plummer FA, Kimani J, Dong T, Kiama P, Rostron T, Njagi E, MacDonalds KS, Bwayo JJ, McMichael AJ, Rowland-Jones SL (2000) HIV-1-specific mucosal CD8+ lymphocyte responses in the cervi of HIV-1-resistant prostitutes in Nairobi. J Immunol 164: 1602–1611PubMedGoogle Scholar
  33. 33.
    Makedonas G, Bruneau J, Lin H, Sekaly RP, Lamothe F, Bernard NF (2002) HIV-specific CD8 T-cell activity in uninfected injection drug use is associated with maintenance of seronegativity. AIDS 16: 1595–1602PubMedCrossRefGoogle Scholar
  34. 34.
    Promadej N, Costello C, Wernett MM, Kulkarni PS, Robinson VA, Nelso KE, Hodge TW, Suriyanon V, Duerr A, McNicholl JM (2003) Broad human immunodeficiency virus (HIV)-specific T cell responses to conserved HIV proteins in HIV-seronegative women highly exposed to a single HIV-infected partner. J Infect Dis 187: 1053–1063PubMedCrossRefGoogle Scholar
  35. 35.
    Kaul R, Rowland-Jones SL, Kimani J, Fowke K, Dong T, Kiama P, Rutherford J, Njagi E, Mwangi F, Rostron T, Onyango J, Oyugi J, MacDonald KS, Bwayo JJ, Plummer FA (2001) New insights into HIV-1 specific cytotoxic T-lymphocyte responses in exposed, persistently seronegative Kenyan sex workers. Immunol Lett 79: 3–13PubMedCrossRefGoogle Scholar
  36. 36.
    Clerici M, Giorgi JV, Chou C et al (1992) Cell mediated immune response to Human Immunodeficiency Virus (HIV) Type 1 in seronegative homosexual men with recent sexual exposure to HIV-1. J Infec Dis 165: 1012–1019Google Scholar
  37. 37.
    Makedonas G, Bruneau J, Lin H, Sekaly RP, Lamothe F, Bernard NF (2002) HIV-specific CD8 T-cell activity in uninfected injection drug users is associated with maintenance of seronegativity. AIDS 16: 1595–1602PubMedCrossRefGoogle Scholar
  38. 38.
    Kaul R, Rowland-Jones SL et al (2001) Late seroconversion in HIV-resistant Naibori prostitutes despite pre-existing HIV-specific CD8(+) responses. J Clin Invest 107: 341–349PubMedCrossRefGoogle Scholar
  39. 39.
    Scott-Algara D, Truong LX, Versmisse P, David A, Luong TT, Nguyen NV, Theodorou I, Barre-Sinoussi F, Pancino G (2003) Cutting edge: increased NK cell activity in HIV-1-exposed but uninfected Vietnamese intravascular drug users. J Immunol 71: 5663–5667Google Scholar
  40. 40.
    Shieh B, Yan YP, Ko NY, Liau YE, Liu YC, Lin HH, Chen PP, Li C (2001) Detection of elevated serum beta-chemokine levels in seronegative Chinese individuals exposed to human immunodeficiency virus type 1. Clin Infect Dis 33: 273–279PubMedCrossRefGoogle Scholar
  41. 41.
    Biasin M, Caputo SL, Speciale L, Colombo F et al (2000) Mucosal and systemic immune activation is present in human immunodeficiency virus-exposed seronegative women. J Infect Dis 182: 1365–1374PubMedCrossRefGoogle Scholar
  42. 42.
    Devito C, Hinkula J, Kaul R, Lopalco L et al (2000) Mucosal and plasma IgA from HIV-exposed seronegative individuals neutralize a primary HIV-1 isolate. AIDS 14: 1917–1920PubMedCrossRefGoogle Scholar
  43. 43.
    Mazzoli S, Lopalco L, Salvi A, Trabattoni D, Lo Caputo S, Semplici F, Biasin M, Bl C, Cosma A, Pastori C, Meacci F, Mazzotta F, Villa ML, Siccardi AG, Clerici M (1999) Human immunodeficiency virus (HIV)-specific IgA and HIV neutralizing activity in the serum of exposed seronegative partners of HIV-seropositive persons. J Infect Dis 180: 871–875PubMedCrossRefGoogle Scholar
  44. 44.
    Nicastri E, Sarmati L, Ercoli L, Mancino G, D‘Ambrosio E, d‘Ettorre G, Mastroianni CM, Vullo V, Andreoni M (1999) Reduction of IFN-gamma and IL-2 production by peripheral lymphocytes of HIV-exposed seronegative subjects. AIDS 13: 1333–1336PubMedCrossRefGoogle Scholar
  45. 45.
    Truong LX, Luong TT, Scott-Algara D, Versmisse P, David A, Perez-Bercoff D, Nguyen NV, Tran HK, Cao CT, Fontanet A, Follezou JY, Theodorou I, Barre-Sinoussi F, Pancino G (2003) CD4 cell and CD8 cell-mediated resistance to HIV-1 infection in exposed uninfected intravascular drug users in Vietnam. AIDS 17: 1425–1434PubMedCrossRefGoogle Scholar
  46. 46.
    Broliden K, Hinkula J, Devito C, Kiama P, Kimani J, Trabbatoni D, Bwayo JJ, Clerici M, Plummer F, Kaul R (2001) Functional HIV-1 specific IgA antibodies in HIV-1 exposed, persistently IgG seronegative female sex workers. Immunol Lett 79: 29–36PubMedCrossRefGoogle Scholar
  47. 47.
    Lo Caputo S, Trabattoni D, Vichi F, Piconi S, Lopalco L, Villa ML, Mazzotta F, Clerici M (2003) Mucosal and systemic HIV-1-specific immunity in HIV-1-exposed but uninfected heterosexual men. AIDS 17: 531–539PubMedCrossRefGoogle Scholar
  48. 48.
    John R, Arango-Jaramillo S, Finny GJ, Schwartz DH (2004) Risk associated HIV-1 cross-clade resistance of whole peripheral blood mononuclear cells from exposed uninfected individuals with wild-type CCR5. J Acquir Immune Defic Syndr 35: 1–8PubMedGoogle Scholar
  49. 49.
    Paxton WA, Martin SR, Tse D et al (1996) Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposures. Nat Med 2: 412–417PubMedCrossRefGoogle Scholar
  50. 50.
    Beyrer C, Artenstein AW, Rugpao S, Stephens H, Van Cott TC, Robb ML, Rinkaew M, Birx DL, Khamboonruang C, Zimmerman PA, Nelson KE, Natpratan C (1999) Epidemiologic and biologic characterization of a cohort of human immunodeficiency virus type 1 highly exposed, persistently seronegative female sex workers in northern Thailand. Chiang Mai HEPSWorking Group. J Infect Dis 179: 59–67PubMedCrossRefGoogle Scholar
  51. 51.
    Furci L, Lopalco L, Loverro P, Sinnone M, Tambussi G, Lazzarin A, Lusso P (2002) Non-cytotoxic inhibition of HIV-1 infection by unstimulated CD8+T lymphocytes from HIV-exposed-uninfected individuals. AIDS 16: 1003–1008PubMedCrossRefGoogle Scholar
  52. 52.
    Ghys PD, Belec L, Diallo MO, Ettiegne-Traore V, Becquart P, Maurice C, Nkengasong JN, Coulibaly IM, Greenberg AE, Laga M, Wiktor SZ (2000) Cervicovaginal anti-HIV antibodies in HIV-seronegative female sex workers in Abidjan, Cote d‘Ivoire. AIDS 14: 2603–2608PubMedCrossRefGoogle Scholar
  53. 53.
    Devito C, Broliden K, Kaul R, Svensson L, Johansen K, Kiama P, Kimani J, Lopalco L, Piconi S, Bwayo JJ, Plummer F, Clerici M, Hinkula J (2000) Mucosal and plasma IgA from HIV-1-exposed uninfected individuals inhibit HIV-1 transcytosis across human epithelial cells. J Immunol 165: 5170–5176PubMedGoogle Scholar
  54. 54.
    Belec L, Ghys PD, Hocini H, Nkengasong JN, Tranchot-Diallo J, Diallo MO, Ettiegne-Traore V, Maurice C, Becquart P, Matta M, Si-Mohamed A, Chomont N, Coulibaly IM, Wiktor SZ, Kazatchkine MD (2001) Cervicovaginal secretory antibodies to human immunodeficiency virus type 1 (HIV-1) that block viral transcytosis through tight epithelial barriers in highly exposed HIV-1-seronegative African women. J Infect Dis 184: 1412–1422PubMedCrossRefGoogle Scholar
  55. 55.
    Kaul R, Plummer F, Clerici M, Bomsel M, Lopalco L, Broliden K (2001) Mucosal IgA in exposed, uninfected subjects: evidence for a role in protection against HIV infection. AIDS 15: 431–432PubMedCrossRefGoogle Scholar
  56. 56.
    Buchacz K, Parekh BS, Padian NS, van der Straten A, Phillips S, Jonte J, Holmberg SD (2001) HIV-specific IgG in cervicovaginal secretions of exposed HIV-uninfected female sexual partners of HIV-infected men. AIDS Res Hum Retroviruses 17: 1689–1693PubMedCrossRefGoogle Scholar
  57. 57.
    Devito C, Hinkula J, Kaul R, Kimani J, Kiama P, Lopalco L, Barass C, Piconi S, Trabattoni D, Bwayo JJ, Plummer F, Clerici M, Broliden K (2002) Cross-clade HIV-1-specific neutralizing IgA in mucosal and systemic compartments of HIV-1-exposed, persistently seronegative subjects. J Acquir Immune Defic Syndr 30: 413–420PubMedGoogle Scholar
  58. 58.
    Clerici M, Barassi C, Devito C, Pastori C, Piconi S, Trabattoni D, Longhi R, Hinkula J, Broliden K, Lopalco L (2002) Serum IgA of HIV-exposed uninfected individuals inhibit HIV through recognition of a region within the alpha-helix of gp41. AIDS 16: 1731–1741PubMedCrossRefGoogle Scholar
  59. 59.
    Wright PF, Kozlowski PA, Rybczyk GK, Goepfert P, Staats HF, VanCott TC, Trabattoni D, Sannella E, Mestecky J (2002) Detection of mucosal antibodies in HIV type 1-infected individuals. AIDS Res Hum Retroviruses 18: 1291–1300PubMedCrossRefGoogle Scholar
  60. 60.
    Puro V, Calcagno G, Anselmo M, Benvenuto G et al (2000) Transient detection of plasma HIV-1 RNA during postexposure prophylaxis. Infect Control Hosp Epidemiol 21: 529–531PubMedCrossRefGoogle Scholar
  61. 61.
    Ruprecht RM, Baba TW, Rasmussen R, Hu Y, Sharma PL (1996) Murine and simian retrovirus models: the threshold hypothesis. Aids 10[Suppl] A: 33CrossRefGoogle Scholar
  62. 62.
    Baba TW, Jeong YS, Renninck D, Bronson R, Green MF, Ruprecht RM (1995) Pathogenecity of live, attenuated SIV after mucosal infection of neonatal macaques. Science 267: 1820–1825PubMedGoogle Scholar
  63. 63.
    Obert LA, Hoover EA (2000) Feline immunodeficiency virus clade C mucosal transmission and disease courses. AIDS Res Hum Retroviruses 16: 677PubMedCrossRefGoogle Scholar
  64. 64.
    McChesney MB, Collins JR, Lu D, Lu X, Torten J, Ashely RL, Cloyd MW, Miller CJ (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: 10029PubMedGoogle Scholar
  65. 65.
    Race EM, Ramsey KM, Lucia HL, Cloyd MW (1991) Human Immunodeficiency virus infection elicits early antibody not detected by standard tests: implications for diagnostics and viral immunology. Virology 184: 716–722PubMedCrossRefGoogle Scholar
  66. 66.
    Chen JJ, Wang YL, Chen JY, Shau GK, Tyring S, Ramsey KM, Indrikovs AJ, Peterson JR, Paar D, Cloyd MW (2002) Detection of anti-HIV antibodies which recognize conformational epitopes of gp41/160 allows early diagnosis of HIV infection. J Inf Dis 186: 321–331CrossRefGoogle Scholar
  67. 67.
    Brookmeyer R, Gail MH (1994) AIDS epidemiology: a quantitive approach. Oxford University Press, New YorkGoogle Scholar
  68. 68.
    Kaul R, Towland-Jones SL et al (2001) Late seroconversion in HIV-resistant Naibori prostitutes despite pre-existing HIV-specific CD8(+) responses. J Clin InvestGoogle Scholar
  69. 69.
    Clerici M, Clark EA, Policano P et al (1994) T-cell proliferation to subinfectious SIV correlates with lack of infection after challenge of macaques. AIDS 8: 1391–1395PubMedGoogle Scholar
  70. 70.
    Rosenberg ES, Altfeld M, Poon SH et al (2000) Immune control of HIV-1 after early treatment of acute infection. Nature 407: 523–526PubMedCrossRefGoogle Scholar
  71. 71.
    Zazzi M, Romano L, Brasini A, Valensin PE (1993) Simultaneous amplification of multiple HIV-1 DNA sequences from clinical specimens by using nested-primer polymerase chain reaction. AIDS Res Hum Retroviruses 9: 315–320PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 2005

Authors and Affiliations

  • G. K. Sahu
    • 1
  • T. McNearney
    • 3
  • A. Evans
    • 1
  • A. Turner
    • 1
  • S. Weaver
    • 2
  • J. C. Huang
    • 1
  • S. Baron
    • 1
  • D. Paar
    • 3
  • M. W. Cloyd
    • 1
    • 2
  1. 1.Department of Microbiology & ImmunologyUniversity of Texas Medical BranchGalvestonUSA
  2. 2.Department of PathologyUniversity of Texas Medical BranchGalvestonUSA
  3. 3.Department of Internal MedicineUniversity of Texas Medical BranchGalvestonUSA

Personalised recommendations