Retrospective analysis of viral load and SIV antibody responses in rhesus macaques infected with pathogenic SIV:
S M Smith1, B Holland, C Russo
1St Michael's Medical Center, Newark, New Jersey 07102, USA. ssmith1824@aol.com
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 (> or =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 10(5) 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, microencapuslated SIV vaccine reduced viral load without affecting clinical outcome. This latter finding may have implications for the evaluation of HIV-1 human vaccine trials.
Insights
High simian immunodeficiency virus (SIV) plasma viral load predicts faster disease progression in macaques. Chronic phase viral load is the strongest indicator, while a specific vaccine reduced viral load but not disease outcome.
Area of Science:
- Veterinary Virology
- Immunology
- Primate Models
Background:
- Prognostic significance of simian immunodeficiency virus (SIV) plasma viral load in macaques is not well-established.
- Rapid disease progression is often observed in animals lacking an anti-SIV humoral response.
Purpose of the Study:
- To determine the prognostic significance of viral load and seroconversion in SIV-infected rhesus macaques.
- To evaluate the impact of a formalin-fixed, microencapsulated SIV vaccine on viral load and disease progression.
Main Methods:
- Retrospective analysis of plasma viral load and serology data from 74 SIVmac-infected rhesus macaques.
- Viral load measured at peak (days 7-21), acute (days 30-55), and chronic (days 80-100) postinfection.
- Clinical outcome defined as rapid (<1 year) or slow (>=1 year) disease progression.
Main Results:
- High peak and acute viral loads were associated with more rapid disease development (p = 0.0086, p = 0.0004).
- Acute viral load was more strongly associated with rapid progression when analyzed with peak viral load (p = 0.03).
- Slow progression correlated with chronic viral loads below 3.47 x 10^5 RNA copies/ml.
- Vaccinated animals had lower peak viral loads but similar disease progression rates compared to unvaccinated controls.
Conclusions:
- Viral load is a significant prognostic indicator for SIV disease progression rate in naive animals.
- Chronic phase viral load (days 80-100) is most closely associated with disease progression.
- A formalin-fixed, microencapsulated SIV vaccine reduced viral load but did not alter clinical outcome, suggesting implications for HIV-1 vaccine trial evaluations.
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