Document Detail


Depo-provera treatment does not abrogate protection from intravenous SIV challenge in female macaques immunized with an attenuated AIDS virus.
MedLine Citation:
PMID:  20352116     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In a previous study, progesterone treatment of female monkeys immunized with live, attenuated SHIV89.6 abrogated the generally consistent protection from vaginal simian immunodeficiency virus (SIV) challenge. The mechanisms responsible for the loss of protection remain to be defined. The objective of the present study was to determine whether Depo-Provera administration alters protection from intravenous SIV challenge in SHIV-immunized female macaques.
METHODS AND FINDINGS: Two groups of female macaques were immunized with attenuated SHIV89.6 and then challenged intravenously with SIVmac239. Four weeks before challenge, one animal group was treated with Depo-Provera, a commonly used injectable contraceptive progestin. As expected, SHIV-immunized monkeys had significantly lower peak and set-point plasma viral RNA levels compared to naïve controls, but in contrast to previously published findings with vaginal SIV challenge, the Depo-Provera SHIV-immunized animals controlled SIV replication to a similar, or even slightly greater, degree than did the untreated SHIV-immunized animals. Control of viral replication from week 4 to week 20 after challenge was more consistent in the progesterone-treated, SHIV-immunized animals than in untreated, SHIV-immunized animals. Although levels of interferon-gamma production were similar, the SIV-specific CD8(+) T cells of progesterone-treated animals expressed more functions than the anti-viral CD8(+) T cells from untreated animals.
CONCLUSIONS: Depo-Provera did not diminish the control of viral replication after intravenous SIV challenge in female macaques immunized with a live-attenuated lentivirus. This result contrasts with the previously reported effect of Depo-Provera(R) on protection from vaginal SIV challenge and strongly implies that the decreased protection from vaginal challenge is due to effects of progesterone on the genital tract rather than to systemic effects. Further, these results demonstrate that the effects of hormonal contraceptives on vaccine efficacy need to be considered in the context of testing and use of an AIDS vaccine.
Authors:
Meritxell Genescà; Michael B McChesney; Christopher J Miller
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-03-23
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-03-30     Completed Date:  2011-01-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e9814     Citation Subset:  IM    
Affiliation:
Center for Comparative Medicine, University of California Davis, Davis, California, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
CD4-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / metabolism
Contraceptive Agents, Female / pharmacology
Female
Flow Cytometry / methods
HIV / genetics*
Leukocytes, Mononuclear / cytology
Macaca
Medroxyprogesterone Acetate / pharmacology*
RNA, Viral / metabolism
Simian immunodeficiency virus / metabolism*
Transforming Growth Factor alpha / metabolism
Transforming Growth Factor beta / metabolism
Vaccines, Attenuated / immunology
Grant Support
ID/Acronym/Agency:
AI066314/AI/NIAID NIH HHS; AI44480/AI/NIAID NIH HHS; RR00169/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Contraceptive Agents, Female; 0/RNA, Viral; 0/Transforming Growth Factor alpha; 0/Transforming Growth Factor beta; 0/Vaccines, Attenuated; 71-58-9/Medroxyprogesterone Acetate
Comments/Corrections

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