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 language | English (US) |
|---|---|
| Pages (from-to) | 1691-1701 |
| Number of pages | 11 |
| Journal | AIDS research and human retroviruses |
| Volume | 15 |
| Issue number | 18 |
| DOIs | |
| State | Published - Dec 10 1999 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Immunology
- Virology
- Infectious Diseases
Cite this
}
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 journal › Article
TY - JOUR
T1 - Retrospective analysis of viral load and SIV antibody responses in rhesus macaques infected with pathogenic SIV
T2 - Predictive value for disease progression
AU - Smith, Stephen M.
AU - Holland, Bart
AU - Russo, Christine
AU - Dailey, Peter J.
AU - Marx, Preston A.
AU - Connor, Ruth I.
PY - 1999/12/10
Y1 - 1999/12/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032764952&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032764952&partnerID=8YFLogxK
U2 - 10.1089/088922299309739
DO - 10.1089/088922299309739
M3 - Article
C2 - 10606092
AN - SCOPUS:0032764952
VL - 15
SP - 1691
EP - 1701
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
SN - 0889-2229
IS - 18
ER -