Post-exposure prophylaxis for SIV revisited: Animal model for HIV prevention

ResearchWorks/Manakin Repository

Search ResearchWorks


Advanced Search

Browse

My Account

Statistics

Related Information

Post-exposure prophylaxis for SIV revisited: Animal model for HIV prevention

Show simple item record

dc.contributor.author Emau, Peter en_US
dc.contributor.author Jiang, Yonghou en_US
dc.contributor.author Agy, Michael B. en_US
dc.contributor.author Tian, Baoping en_US
dc.contributor.author Bekele, Girma en_US
dc.contributor.author Tsai, Che-Chung en_US
dc.date.accessioned 2010-04-21T15:54:59Z
dc.date.available 2010-04-21T15:54:59Z
dc.date.issued 2006 en_US
dc.identifier.citation Emau P, Jiang Y, Agy M, et al. Post-exposure prophylaxis for SIV revisited: Animal model for HIV prevention. AIDS Research and Therapy. 2006;3(1):29. en_US
dc.identifier.other 10.1186/1742-6405-3-29 en_US
dc.identifier.uri http://www.aidsrestherapy.com/content/3/1/29 en_US
dc.identifier.uri http://hdl.handle.net/1773/15766
dc.description.abstract Background: A 4-week, uninterrupted treatment with 9-(2-phosphonyl-methoxypropyly)adenine (PMPA, commonly called tenofovir) completely prevents simian immunodeficiency virus (SIVmne) infection in cynomolgus macaques if treatment begins within 24 hours after SIVmne inoculation, but is less effective if treatment is delayed or duration of treatment is shortened. Critical factors for efficacy include timing and duration of treatment, potency of antiretroviral drug and a contribution from antiviral immune responses. Therefore, we evaluated the impact of one or more treatment interruptions plus SIVmne reexposures on efficacy of PMPA treatment to prevent SIVmne infection in cynomolgus macaques. We also evaluated whether macaques with pre-existing SIV immune responses show increased efficacy of treatment. Eight PMPA-treated, virus-negative and seronegative macaques, and five PMPA-treated, virusnegative but weakly or strongly seropositive macaques were re-inoculated with SIVmne and treated with PMPA starting 24 hr post inoculation. Thereafter, they received either a 5-week treatment involving one interruption plus one SIVmne challenge or a 10-week treatment involving six interruptions plus six SIVmne challenges early during treatment. Parameters measured were plasma SIV RNA, SIV-antibody response, CD4+ T lymphocyte subsets and in vivo CD8+ cell-suppression of virus infection. Results: All seronegative macaques developed persistent antibody response beginning 4 to 8 weeks after stopping PMPA-treatment in absence of viremia in a majority of macaques and coinciding with onset of intermittent viremia in other macaques. In contrast, all weakly or strongly seropositive macaques showed immediate increase in titers (> 1600) of SIV antibodies, even before the end of PMPA-treatment, and in absence of detectable viremia. However, in vivo CD8+ -cell depletion revealed CD8 cell-suppression of viremia and persistence of virus in the macaques as long as 2 years after PMPA-treatment, even in aviremic macaques. Unlike untreated macaques, a treated macaque controlled viral replication and blocked CD4+ T cell depletion when challenged with a heterologus chimeric SIV/HIV-1 virus called SHIV89.6P. Conclusion: A single interruption plus one SIVmne challenge was as sufficient as six interruptions plus six SIVmne challenges in reducing efficacy of PMPA, but results in long-term persistence of virus infection suppressed by CD8+ cells. Efficacy of PMPA treatment was highest in macaques with pre-existing SIV immune responses. en_US
dc.description.sponsorship This work was partially supported by NIH-NIAID contracts AI-65311 and AI-15450 and NIH grant RR-00166. en_US
dc.language.iso en_US en_US
dc.title Post-exposure prophylaxis for SIV revisited: Animal model for HIV prevention en_US
dc.type Article en_US


Files in this item

Files Size Format View
1742-6405-3-29.pdf 378.6Kb PDF View/Open

This item appears in the following Collection(s)

Show simple item record