Presenter: Jingyi Li

Authors: Jingyi (Jenny) Li1, Natalie Castell2, Katie Mulka2, Rebecca Veenhuis2, Janice Clements2
1Tufts University, North Grafton, MA, USA, 2Johns Hopkins University, Baltimore, MD, USA

Background: There are known sex differences in HIV infection. Women with HIV (WWH) have increased immune activation, lower acute viral loads, and progress more rapidly to AIDS compared to men. Additionally, WWH are more prone to neurocognitive impairment (NCI) suggesting a sex-difference in the effect HIV has on the central nervous system (CNS). However, there have been no studies that have examined sex differences in immune cells within the CNS in people living with HIV.

Objective: To investigate the role biological sex plays in the innate immune response to HIV in the CNS utilizing the SIV-infected ART-suppressed macaque model of HIV.

Methods: Basal ganglia and spleen (control) tissues were compared between six female and six male SIV-infected ART-suppressed rhesus macaques. All animals were inoculated with SIVmac251, and began daily anti-retroviral therapy (ART: DTG/PMPA/TDF) 14 days post inoculation. Terminal time-points were completed at 300dpi after 8 months of suppression. At euthanasia, macaques were perfused with saline. Tissue samples were fixed, paraffin-embedded and sectioned onto positively charged slides. Immunohistochemistry for Iba-1  was completed to assess the number of brain macrophages present in each group. All samples were analyzed using digital image analysis software, Qupath.

Results: Female SIVmac251-infected ART suppressed macaques had higher numbers of brain macrophages in basal ganglia compared to male counterparts. No differences were observed in spleen.

Conclusion: Our findings suggest that SIV-infected ART-suppressed female macaques may have more robust innate immune responses in the CNS compared to males. These data may explain the observation of greater NCI in WWH.

Keyword: Primate

Presentation Date: 11/12/22