T-cell subset differentiation and antibody responses following antiretroviral therapy during simian immunodeficiency virus infection

Antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) infection represents a major breakthrough in the treatment of HIV/acquired immune-deficiency syndrome. However, it remains unclear how ART influences virus-specific immune responses and understanding this is important for developing novel cure and eradication interventions for HIV-1. In the present study, we evaluate how ART impacts T-cell and antibody responses in simian immunodeficiency virus (SIV) -infected rhesus macaques. We evaluated CD4 and CD8 T-cell responses by multiparameter flow cytometry, viral loads by quantitative RT-PCR by a two-step process using SIV-specific primers and antibody neutralization function by luciferase-based TZM-bl assays. We demonstrate that macaques treated with ART exhibit phenotypic and qualitative effects on T-cell and antibody responses. Macaques on ART exhibited low numbers of virus-specific T-cell responses, and these responses appeared to be partially biased towards central memory subsets. More importantly, there were significantly reduced neutralizing antibody responses in macaques treated with ART. Collectively, these data improve the understanding of how virus-specific immune responses are generated during ART, and suggest the potential importance of therapeutic vaccines to maintain adaptive immunity during treated infection.