Retrospective analysis of viral load and SIV antibody responses in rhesus macaques infected with pathogenic SIV: Predictive value for disease progression

Stephen M. Smith, Bart Holland, Christine Russo, Peter J. Dailey, Preston A. Marx, Ruth I. Connor

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Abstract

The prognostic significance of SIV plasma viral load in macaques has not been well established, primarily owing to the small numbers of animals in experimental groups. In addition, many investigators have noted that animals that fail to develop an anti-SIV humoral response develop disease rapidly. To establish the prognostic significance of viral load and seroconversion, we retrospectively analyzed the plasma viral load and serology data from 74 rhesus macaques infected with SIVmac. Viral load was analyzed at three time points: in the peak (days 7-21), acute (days 30-55), and chronic (days 80- 100) periods postinfection. High viral load in the peak and acute phases was associated with more rapid development of disease (p = 0.0086, p = 0.0004, respectively). We defined clinical outcome as rapid (<1 year) or slow (≥1 year) progression. When peak and acute viral loads were analyzed together, acute viral load was more strongly associated with rapid progression (p = 0.03). Slow progression was strongly associated with chronic viral loads below the median of 3.47 x 105 RNA copies/ml. Despite having preexisting anti-SIV antibodieS, 7 of 23 vaccinated animals were rapid progressors. All unvaccinated animals that mounted a humoral response to SIV were slow progressors. Animals that received a formalin-fixed, microencapsulated SIV vaccine prior to infection had lower peak viral loads than unvaccinated animals (p = 0.0005), but developed disease at the same rate. Overall, in naive animals, viral load is an important prognostic indicator of the disease progression rate. We found that viral load measured during the chronic phase (days 80-100) of infection was most closely associated with disease progression. We also found that a formalin-fixed, microencapsulated SIV vaccine reduced viral load without affecting clinical outcome. This latter finding may have implications for the evaluation of HIV-1 human vaccine trials.

Original languageEnglish (US)
Pages (from-to)1691-1701
Number of pages11
JournalAIDS research and human retroviruses
Volume15
Issue number18
DOIs
StatePublished - Dec 10 1999

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Macaca mulatta
Viral Load
Antibody Formation
Disease Progression
SAIDS Vaccines
Formaldehyde
Macaca
Serology
Infection
HIV-1
Anti-Idiotypic Antibodies
Vaccines
Research Personnel
RNA

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

Smith, Stephen M. ; Holland, Bart ; Russo, Christine ; Dailey, Peter J. ; Marx, Preston A. ; Connor, Ruth I. / Retrospective analysis of viral load and SIV antibody responses in rhesus macaques infected with pathogenic SIV : Predictive value for disease progression. In: AIDS research and human retroviruses. 1999 ; Vol. 15, No. 18. pp. 1691-1701.
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abstract = "The prognostic significance of SIV plasma viral load in macaques has not been well established, primarily owing to the small numbers of animals in experimental groups. In addition, many investigators have noted that animals that fail to develop an anti-SIV humoral response develop disease rapidly. To establish the prognostic significance of viral load and seroconversion, we retrospectively analyzed the plasma viral load and serology data from 74 rhesus macaques infected with SIVmac. Viral load was analyzed at three time points: in the peak (days 7-21), acute (days 30-55), and chronic (days 80- 100) periods postinfection. High viral load in the peak and acute phases was associated with more rapid development of disease (p = 0.0086, p = 0.0004, respectively). We defined clinical outcome as rapid (<1 year) or slow (≥1 year) progression. When peak and acute viral loads were analyzed together, acute viral load was more strongly associated with rapid progression (p = 0.03). Slow progression was strongly associated with chronic viral loads below the median of 3.47 x 105 RNA copies/ml. Despite having preexisting anti-SIV antibodieS, 7 of 23 vaccinated animals were rapid progressors. All unvaccinated animals that mounted a humoral response to SIV were slow progressors. Animals that received a formalin-fixed, microencapsulated SIV vaccine prior to infection had lower peak viral loads than unvaccinated animals (p = 0.0005), but developed disease at the same rate. Overall, in naive animals, viral load is an important prognostic indicator of the disease progression rate. We found that viral load measured during the chronic phase (days 80-100) of infection was most closely associated with disease progression. We also found that a formalin-fixed, microencapsulated SIV vaccine reduced viral load without affecting clinical outcome. This latter finding may have implications for the evaluation of HIV-1 human vaccine trials.",
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Retrospective analysis of viral load and SIV antibody responses in rhesus macaques infected with pathogenic SIV : Predictive value for disease progression. / Smith, Stephen M.; Holland, Bart; Russo, Christine; Dailey, Peter J.; Marx, Preston A.; Connor, Ruth I.

In: AIDS research and human retroviruses, Vol. 15, No. 18, 10.12.1999, p. 1691-1701.

Research output: Contribution to journalArticle

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