SIV-specific T lymphocyte responses in PBMC and lymphoid tissues of SIV-infected pigtailed macaques during suppressive combination antiretroviral therapy.
There is currently no SIV macaque model in which the effects of combination antiretroviral therapy on tissue immune responses and latent reservoirs have been measured. This study was performed to define the impact of combination therapy on the specificity and distribution of the T lymphocyte response in multiple tissue compartments. Pigtailed macaques (Macaca nemestrina) were infected with SIV/17E-Fr and treated with combination antiretroviral therapy consisting of 9-R-(2-phosphonomethoxypropyl)adenine (PMPA) and beta-2',3'-dideoxy-3'-thia-5-fluorocytidine (FTC). The SIV-specific T lymphocyte response was measured in peripheral blood, spleen and several lymph nodes at necropsy by IFN-gamma Elispot analysis. Two animals (one treated, one untreated) had high acute peak viremia, which was associated with lower SIV-specific T lymphocyte responses in the peripheral blood and lymphoid tissues. In the treated animal, viremia was controlled to low or undetectable for the study duration, and virus-specific responses remained low. The untreated animal remained viremic throughout the study and developed clinical symptoms of AIDS. In contrast, the two animals that had lower acute peak viremia (one treated, one untreated) had more robust T lymphocyte responses, and controlled viral replication. Virus-specific responses were detected in the treated animal despite 6 months of suppressive therapy. These data suggest that in this model, in the context of acute peak viremia and weak T cell responses, combination therapy may be essential to control virus replication and disease progression. Conversely, in the setting of low initial viremia and robust T lymphocyte responses, treatment does not have a detrimental effect on the immune response.
Carruth
Lucy M
LM
Department of Comparative Medicine, Johns Hopkins University School of Medicine, Jefferson Street Building, 600 N. Wolfe Street, Baltimore, MD 21287, USA. lcarruth@jhmi.edu
Zink
M Christine
MC
Tarwater
Patrick M
PM
Miller
Michael D
MD
Li
Ming
M
Queen
Laurie A
LA
Mankowski
Joseph L
JL
Shen
Anding
A
Siliciano
Robert F
RF
Clements
Janice E
JE
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D044966:Anti-Retroviral Agents / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068679:Emtricitabine / Q000031:analogs & derivatives; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D016014:Linear Models; D008254:Macaca nemestrina; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use; D018419:Primate Diseases / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D015302:Simian Immunodeficiency Virus; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D000068698:Tenofovir; D014766:Viremia / Q000188:drug therapy / Q000662:veterinary; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D016047:Zalcitabine; D007371:Interferon-gamma; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; C075889:Racivir