HIV-1 clade C-derived SHIV-C109 viral infection and response to antiretroviral drug therapy in humanized mice

Simian-human immunodeficiency viruses (SHIVs) are commonly used as surrogates in NHP models for HIV-related studies. Most SHIV studies focused on HIV-1 clade B, although clade C is more prevalent, especially in low-resource regions outside of North America. Here we evaluated SHIV-C109 infection dynamics and antiretroviral therapy (ART) in a dual-purpose hu-HSC humanized mouse model permissive for both HIVs and SIVs. SHIV-C109 comprises a SHIVHXBc2 P3.2 backbone with an R5-tropic HIV-1 clade C envelope. Hu-HSC mice from multiple immune cohorts were inoculated with SHIV-C109 and monitored for a prolonged period to determine the persistence of viremia and CD4 + T-cell decline. Our results showed successful infection and sustained viremia for >45 weeks. RNAscope analysis showed disseminated viral infection in lymphoid organs such as the spleen and lymph nodes. CD4 + T-cell depletion was observed during the chronic infection phase. As a prelude to translation to the NHP model, we also assessed the efficacy of antiretroviral therapy on this virus using the hu-HSC mouse model. Antiretroviral drugs bictegravir, emtricitabine, and tenofovir alafenamide were administered via diet. Viral suppression was achieved in all treated mice for several weeks. These results support the potential value of the hu-HSC mouse model in preclinical studies on HIV-1 clade C viruses. Importantly, comparative cure studies on both HIV and SIV can now be conducted using the same animal model.