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Journal of Virology logoLink to Journal of Virology
. 1997 Jan;71(1):284–290. doi: 10.1128/jvi.71.1.284-290.1997

Plasma viremia in macaques infected with simian immunodeficiency virus: plasma viral load early in infection predicts survival.

A Watson 1, J Ranchalis 1, B Travis 1, J McClure 1, W Sutton 1, P R Johnson 1, S L Hu 1, N L Haigwood 1
PMCID: PMC191049  PMID: 8985348

Abstract

A reliable method for the quantitation of plasma viremia in nonhuman primates infected with simian immunodeficiency virus (SIV) and related viruses is described. This method is based on an established quantitative-competitive PCR format and includes a truncated control for internal assay calibration. Optimization of assay conditions has significantly improved amplification specificity, and interassay variability is comparable to that of commercially available assays for human immunodeficiency virus (HIV) quantitation. This procedure was used to monitor viral loads in a group of Macaca mulatta animals that were infected with SIVsmE660 for over 2 years. Highly diverse profiles of plasma viremia were observed among animals, and high viral loads were associated with more rapid disease progression. Spearman rank correlation analyses were done for survival versus three parameters of viral load: plasma viremia, p27 core antigen, and frequency of infected peripheral blood mononuclear cells. Plasma viremia had the strongest overall correlation and was significantly (P < 0.05 to P < 0.01) associated with survival at 10 of the 13 time points examined. Plasma viremia did not correlate with survival during the primary viremia phase; however, the strength of this correlation increased with time postinfection and, remarkably, viremia levels as early as week 6 postinfection were highly predictive (P < 0.01) of relative survival. These findings are consistent with the available clinical data concerning viral load correlates early in HIV infection, and they provide further support for the view that disease outcome in lentiviral infection may be largely determined by events that occur shortly after infection.

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Selected References

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  1. Aoki-Sei S., Yarchoan R., Kageyama S., Hoekzema D. T., Pluda J. M., Wyvill K. M., Broder S., Mitsuya H. Plasma HIV-1 viremia in HIV-1 infected individuals assessed by polymerase chain reaction. AIDS Res Hum Retroviruses. 1992 Jul;8(7):1263–1270. doi: 10.1089/aid.1992.8.1263. [DOI] [PubMed] [Google Scholar]
  2. Bagnarelli P., Menzo S., Valenza A., Manzin A., Giacca M., Ancarani F., Scalise G., Varaldo P. E., Clementi M. Molecular profile of human immunodeficiency virus type 1 infection in symptomless patients and in patients with AIDS. J Virol. 1992 Dec;66(12):7328–7335. doi: 10.1128/jvi.66.12.7328-7335.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cao Y., Ho D. D., Todd J., Kokka R., Urdea M., Lifson J. D., Piatak M., Jr, Chen S., Hahn B. H., Saag M. S. Clinical evaluation of branched DNA signal amplification for quantifying HIV type 1 in human plasma. AIDS Res Hum Retroviruses. 1995 Mar;11(3):353–361. doi: 10.1089/aid.1995.11.353. [DOI] [PubMed] [Google Scholar]
  4. Cao Y., Qin L., Zhang L., Safrit J., Ho D. D. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med. 1995 Jan 26;332(4):201–208. doi: 10.1056/NEJM199501263320401. [DOI] [PubMed] [Google Scholar]
  5. Cullen B. R. The role of Nef in the replication cycle of the human and simian immunodeficiency viruses. Virology. 1994 Nov 15;205(1):1–6. doi: 10.1006/viro.1994.1613. [DOI] [PubMed] [Google Scholar]
  6. Haigwood N. L., Watson A., Sutton W. F., McClure J., Lewis A., Ranchalis J., Travis B., Voss G., Letvin N. L., Hu S. L. Passive immune globulin therapy in the SIV/macaque model: early intervention can alter disease profile. Immunol Lett. 1996 Jun;51(1-2):107–114. doi: 10.1016/0165-2478(96)02563-1. [DOI] [PubMed] [Google Scholar]
  7. Hammer S., Crumpacker C., D'Aquila R., Jackson B., Lathey J., Livnat D., Reichelderfer P. Use of virologic assays for detection of human immunodeficiency virus in clinical trials: recommendations of the AIDS Clinical Trials Group Virology Committee. J Clin Microbiol. 1993 Oct;31(10):2557–2564. doi: 10.1128/jcm.31.10.2557-2564.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Henrard D. R., Daar E., Farzadegan H., Clark S. J., Phillips J., Shaw G. M., Busch M. P. Virologic and immunologic characterization of symptomatic and asymptomatic primary HIV-1 infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Jul 1;9(3):305–310. [PubMed] [Google Scholar]
  9. Henrard D. R., Phillips J. F., Muenz L. R., Blattner W. A., Wiesner D., Eyster M. E., Goedert J. J. Natural history of HIV-1 cell-free viremia. JAMA. 1995 Aug 16;274(7):554–558. [PubMed] [Google Scholar]
  10. Hirsch V. M., Fuerst T. R., Sutter G., Carroll M. W., Yang L. C., Goldstein S., Piatak M., Jr, Elkins W. R., Alvord W. G., Montefiori D. C. Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara. J Virol. 1996 Jun;70(6):3741–3752. doi: 10.1128/jvi.70.6.3741-3752.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hollinger F. B., Bremer J. W., Myers L. E., Gold J. W., McQuay L. Standardization of sensitive human immunodeficiency virus coculture procedures and establishment of a multicenter quality assurance program for the AIDS Clinical Trials Group. The NIH/NIAID/DAIDS/ACTG Virology Laboratories. J Clin Microbiol. 1992 Jul;30(7):1787–1794. doi: 10.1128/jcm.30.7.1787-1794.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Johnson P. R., Hirsch V. M. SIV infection of macaques as a model for AIDS pathogenesis. Int Rev Immunol. 1992;8(1):55–63. doi: 10.3109/08830189209056641. [DOI] [PubMed] [Google Scholar]
  13. Jurriaans S., Van Gemen B., Weverling G. J., Van Strijp D., Nara P., Coutinho R., Koot M., Schuitemaker H., Goudsmit J. The natural history of HIV-1 infection: virus load and virus phenotype independent determinants of clinical course? Virology. 1994 Oct;204(1):223–233. doi: 10.1006/viro.1994.1526. [DOI] [PubMed] [Google Scholar]
  14. Katzenstein T. L., Pedersen C., Nielsen C., Lundgren J. D., Jakobsen P. H., Gerstoft J. Longitudinal serum HIV RNA quantification: correlation to viral phenotype at seroconversion and clinical outcome. AIDS. 1996 Feb;10(2):167–173. doi: 10.1097/00002030-199602000-00006. [DOI] [PubMed] [Google Scholar]
  15. Kestler H. W., 3rd, Ringler D. J., Mori K., Panicali D. L., Sehgal P. K., Daniel M. D., Desrosiers R. C. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell. 1991 May 17;65(4):651–662. doi: 10.1016/0092-8674(91)90097-i. [DOI] [PubMed] [Google Scholar]
  16. Lin H. J., Myers L. E., Yen-Lieberman B., Hollinger F. B., Henrard D., Hooper C. J., Kokka R., Kwok S., Rasheed S., Vahey M. Multicenter evaluation of quantification methods for plasma human immunodeficiency virus type 1 RNA. J Infect Dis. 1994 Sep;170(3):553–562. doi: 10.1093/infdis/170.3.553. [DOI] [PubMed] [Google Scholar]
  17. Mellors J. W., Kingsley L. A., Rinaldo C. R., Jr, Todd J. A., Hoo B. S., Kokka R. P., Gupta P. Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. Ann Intern Med. 1995 Apr 15;122(8):573–579. doi: 10.7326/0003-4819-122-8-199504150-00003. [DOI] [PubMed] [Google Scholar]
  18. Mellors J. W., Rinaldo C. R., Jr, Gupta P., White R. M., Todd J. A., Kingsley L. A. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science. 1996 May 24;272(5265):1167–1170. doi: 10.1126/science.272.5265.1167. [DOI] [PubMed] [Google Scholar]
  19. Mulder J., McKinney N., Christopherson C., Sninsky J., Greenfield L., Kwok S. Rapid and simple PCR assay for quantitation of human immunodeficiency virus type 1 RNA in plasma: application to acute retroviral infection. J Clin Microbiol. 1994 Feb;32(2):292–300. doi: 10.1128/jcm.32.2.292-300.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pantaleo G., Menzo S., Vaccarezza M., Graziosi C., Cohen O. J., Demarest J. F., Montefiori D., Orenstein J. M., Fox C., Schrager L. K. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Engl J Med. 1995 Jan 26;332(4):209–216. doi: 10.1056/NEJM199501263320402. [DOI] [PubMed] [Google Scholar]
  21. Piatak M., Jr, Saag M. S., Yang L. C., Clark S. J., Kappes J. C., Luk K. C., Hahn B. H., Shaw G. M., Lifson J. D. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science. 1993 Mar 19;259(5102):1749–1754. doi: 10.1126/science.8096089. [DOI] [PubMed] [Google Scholar]
  22. Rinaldo C., Huang X. L., Fan Z. F., Ding M., Beltz L., Logar A., Panicali D., Mazzara G., Liebmann J., Cottrill M. 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. 1995 Sep;69(9):5838–5842. doi: 10.1128/jvi.69.9.5838-5842.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rump J. A., Peter H. H., Schneider J., Haller O., Meyerhans A. Long-term survivors with continuously high levels of HIV type 1. AIDS Res Hum Retroviruses. 1996 Jun 10;12(9):757–758. doi: 10.1089/aid.1996.12.757. [DOI] [PubMed] [Google Scholar]
  24. Saag M. S., Holodniy M., Kuritzkes D. R., O'Brien W. A., Coombs R., Poscher M. E., Jacobsen D. M., Shaw G. M., Richman D. D., Volberding P. A. HIV viral load markers in clinical practice. Nat Med. 1996 Jun;2(6):625–629. doi: 10.1038/nm0696-625. [DOI] [PubMed] [Google Scholar]
  25. Saksela K., Stevens C. E., Rubinstein P., Taylor P. E., Baltimore D. HIV-1 messenger RNA in peripheral blood mononuclear cells as an early marker of risk for progression to AIDS. Ann Intern Med. 1995 Nov 1;123(9):641–648. doi: 10.7326/0003-4819-123-9-199511010-00001. [DOI] [PubMed] [Google Scholar]
  26. Todd J., Pachl C., White R., Yeghiazarian T., Johnson P., Taylor B., Holodniy M., Kern D., Hamren S., Chernoff D. Performance characteristics for the quantitation of plasma HIV-1 RNA using branched DNA signal amplification technology. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10 (Suppl 2):S35–S44. [PubMed] [Google Scholar]
  27. Winters M. A., Tan L. B., Katzenstein D. A., Merigan T. C. Biological variation and quality control of plasma human immunodeficiency virus type 1 RNA quantitation by reverse transcriptase polymerase chain reaction. J Clin Microbiol. 1993 Nov;31(11):2960–2966. doi: 10.1128/jcm.31.11.2960-2966.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wyand M. S. The use of SIV-infected rhesus monkeys for the preclinical evaluation of AIDS drugs and vaccines. AIDS Res Hum Retroviruses. 1992 Mar;8(3):349–356. doi: 10.1089/aid.1992.8.349. [DOI] [PubMed] [Google Scholar]

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