Human immunodeficiency virus type 2 (HIV-2) is less pathogenic and less extensively studied than HIV-1, despite its clinical relevance in West Africa and in countries with socio-colonial ties with West Africa. This dissertation investigates key aspects of HIV-2 biology, focusing on viral integration, susceptibility to antiretroviral agents, and the role of the accessory protein Vpx in host-virus interactions. The antiviral activity of all currently approved integrase strand transfer inhibitors and the capsid inhibitor lenacapavir was evaluated against HIV-2 using cell-based assays and supported by in silico molecular docking analyses. In parallel, transcriptomic and functional approaches were used to examine the effects of HIV-2 Vpx on host gene expression, cytokine secretion, and HIV-1 Tat expression in THP-1 monocytic cells. Furthermore, a comparative genome wide integration site analysis was performed to identify differences between HIV-1 and HIV-2 integration patterns in Jurkat cells. The results demonstrate that HIV-2 is susceptible to integrase strand transfer inhibitors and lenacapavir. Vpx induces broad changes in host transcriptional and inflammatory pathways, and that HIV-2 displays distinct chromatin and chromosomal integration preferences compared with HIV-1. These findings advance understanding of HIV-2 biology and support the use of current and emerging antiretroviral agents for HIV-2 infection.