Abstract Body

Simian immunodeficiency virus (SIV)-infected macaques are an essential animal model for the study of HIV infection, especially in the quest for an effective cure or vaccine. Macaques are a social species, yet are often singly housed for infectious disease research studies. Singly housed uninfected macaques show signs of stress, including decline in CD4+ T cell count and other changes in their immune response. SIV also causes perturbations to the immune response, as reflected most prominently by the decline in CD4+ T cell counts that is commonly used to monitor disease progression, yet the effect of single housing on the progression of SIV infection has yet to be explored. In the context of SIV and HIV, stress has previously been demonstrated to result in lower CD4+ T cell counts, more T cell activation, higher viral loads and increased mortality. We therefore hypothesized that singly housed SIV-infected macaques would demonstrate a greater impact on the immune system and less control of viral replication compared with singly housed SIV-infected macaques.

We compared retrospective data on lymphocyte subset counts, T cell activation and viral loads from 35 singly and 41 socially housed SIV-infected pigtailed macaques (Macaca nemestrina) for three pre-infection timepoints and two post-infection timepoints during acute infection using linear mixed effects regression modeling.

Singly housed macaques demonstrated a more profound decline in the number of circulating CD4+ T cells (P = 0.0012), CD8+ T cells (P = 0.0003) and total lymphocytes (P < 0.0001) throughout acute infection compared to socially housed macaques, with the magnitude of CD4+ T cell decline in socially housed animals more closely mirroring that seen in HIV-infected patients during acute infection. We additionally observed a greater percentage of circulating activated CD69+ CD4+ T cells (P < 0.0001) and CD69+ CD8+ T cells (P < 0.0001) in singly housed macaques. Singly housed macaques furthermore had higher viral loads in the plasma (P < 0.001) and cerebral spinal fluid (P < 0.001) throughout acute infection compared to socially housed macaques, and greater variability in plasma viral load data (P < 0.0001).

Single housing of SIV-infected macaques may provide an exogenous cause of immune modulation and introduce increased variability in data, with the potential to confound results, reduce the translational value of the model and interfere with reproducibility.