title: Initiation of antiretroviral therapy during chronic SIV infection leads to rapid reduction in viral loads and the level of T-cell immune response.
abstract: In the present era of increasing resistance of human immunodeficiency virus (HIV) to antiviral drugs, exploration of adjunct therapies directed at immune responses in combination with antiretroviral drugs may be of value for the treatment of acquired immunodeficiency syndrome. In this study, we designed a model for immune therapy using SIVmac251 infection in rhesus macaques. We explored the outcomes of primary infection on viral loads and the resulting T-cell immune responses in primates. The SIV-infected rhesus macaque model exhibited features similar to those observed in HIV-1 infection of humans. Major histocompatibility complex (MHC) segregation with viral loads were found to associate with viral containment and hence the duration of the disease-free latency period. Thus a better understanding of the relative roles of MHC class I allele in control of viral replication may provide important information for prophylactic or therapeutic vaccine designs. Mamu-A01 is significantly associated with higher immune response and control of viral replication. This allele is frequent in rhesus macaques of Indian origin (22%). Interestingly, Mamu-B01 (26% animals) was associated with lower immune responses and higher viral loads. Another allele, A08 was also predominantly present in 37% of the animals in this study. We observed higher viral replication in individual SIV-infected rhesus monkeys that did not demonstrate strong cellular immune responses. The results are important for understanding SIV disease progression in different MHC Mamu alleles and also for improving the interpretation and quality of pre-clinical studies in rhesus monkeys.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. boyerj@mail.med.upenn.edu
authors.forename: Jean D
authors.initials: JD
authors.lastname: Boyer
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Tara
authors.initials: T
authors.lastname: Robinson
authors.forename: Rose
authors.initials: R
authors.lastname: Parkinson
authors.forename: Ling
authors.initials: L
authors.lastname: Wu
authors.forename: Mark
authors.initials: M
authors.lastname: Lewis
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000483:Alleles; D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D000956:Antigens, Viral / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000254:growth & development*; D019562:Viral Load; D017735:Virus Latency / Q000187:drug effects / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma