Influence of Biological Sex, Age, and HIV Status in an In Vitro Primary Cell Model of HIV Latency Using a CXCR4 Tropic Virus

Primary cell models of human immunodeficiency virus (HIV) latency have become tools to both understand the mechanisms involved in establishment of latency and test preclinical strategies toward HIV-1 cure. These models rely on infection of CD4 T cells from healthy donors. As such, these models provide an opportunity to explore the role of biological sex, age, and HIV status on establishment and reactivation of latent HIV in vitro. We have used an established primary cell model of latency based on the generation of latently infected central memory CD4 T cells with the CXCR4 strain HIV-1(NL)(4-)(3) to address whether these variables influence (i) HIV-1(NL)(4-)(3) replication, (ii) establishment of latency, and (iii) latency reversal in CD4 T cells. Our results indicate that replication of HIV- 1(NL)(4-)(3), but not establishment of latency, is influenced by the age of female, but not male, donors. Moreover, the frequency of latently infected cells in this model is directly correlated with levels of productive infection in both male and female donors independent of age. We did not find differences in the ability of five different latency-reversing agents to reactivate latent HIV-1(NL)(4-)(3). Finally, we have found that this model can be generated using cells from aviremic participants. In conclusion, we have further characterized the central memory T cell model of latency regarding biological sex and age and demonstrated that this model is suitable for use with cells isolated from aviremic participants, opening the opportunity to use this primary cell model to address cure approaches, including shock and kill, in HIV-infected individuals.