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Antiretroviral treatment start-time during primary SIV(mac) infection in macaques exerts a different impact on early viral replication and dissemination
- Source :
- PLoS ONE, Vol 5, Iss 5, p e10570 (2010), PLoS ONE
- Publication Year :
- 2010
- Publisher :
- Public Library of Science (PLoS), 2010.
-
Abstract
- Background The time of infection is rarely known in human cases; thus, the effects of delaying the initiation of antiretroviral therapy (ART) on the peripheral viral load and the establishment of viral reservoirs are poorly understood. Methodology/Principal Findings Six groups of macaques, infected intravenously with SIVmac251, were given placebo or antiretroviral therapy to explore reservoir establishment; macaques were treated for 2 weeks, with treatment starting 4 hours, 7 or 14 days after infection. Viral replication and dissemination were measured in the gut (rectum), in the lung and in blood and lymphoid tissues (peripheral lymph nodes), by quantifying viral RNA, DNA and 2LTR circles. We used immunohistochemistry (CD4 and CD68) to assess the impact of these treatments on the relative amount of virus target cells in tissue. Treatment that was started 4 hours post-infection (pi) decreased viral replication and dissemination in blood and tissue samples, which were assessed on day 14 (RNA/DNA/2LTR circles). The virus remained detectable and lymphoid tissues were activated in LN and the gut in both placebo- and ART-treated animals. Viral RNA in plasma continued to be lower in macaques treated seven days after infection; however, this was not the case for viral DNA in peripheral blood mononuclear cells. There was a small but significant difference in RNA and DNA levels in tissues between placebo- and ART-treated animals on day 21. When started 14 days after infection, treatment resulted in a limited decrease in the plasma viral load. Conclusions Treatment that was started 4 hours after infection significantly reduced viral replication and dissemination. When started 7 days after infection, it was of slight virological benefit in peripheral blood and in tissues, and treatment was even less effective if started 14 days pi. These data favor starting ART no longer than one week after intravenous SIVmac251 exposure.
- Subjects :
- CD4-Positive T-Lymphocytes
Time Factors
Simian Acquired Immunodeficiency Syndrome
Public Health and Epidemiology/Infectious Diseases
Antigens, Differentiation, Myelomonocytic
lcsh:Medicine
Biology
CD8-Positive T-Lymphocytes
Placebo
Virus Replication
Peripheral blood mononuclear cell
Virus
Antigens, CD
Cell Movement
Antiretroviral Therapy, Highly Active
Blood plasma
Cytotoxic T cell
Animals
lcsh:Science
Multidisciplinary
lcsh:R
RNA
Infectious Diseases/HIV Infection and AIDS
Viral Load
Virology
Viral replication
Organ Specificity
Virology/Immunodeficiency Viruses
Immunology
Virology/Animal Models of Infection
Macaca
Simian Immunodeficiency Virus
lcsh:Q
Viral load
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....adbcbf78974fa69280d204c8acc090f9