Immune restoration, activation and viral reservoirs in gut-associated lymphoid tissue in SIV-infected long-term nonprogressing Chinese rhesus macaques on antiretroviral therapy (VIR1P.1130)

Abstract HIV infected long-term nonprogressors (LTNPs) and elite controllers (ECs) maintain enduring control of HIV infection without antiretroviral therapy. However, persistent tissue reservoirs and chronic inflammation still exist. We previously found that 1/3 of SIV-infected Chinese rhesus macaques mimics HIV-infected LTNPs/ECs. Here we studied whether therapy can further decrease tissue reservoirs, restore immune function and decrease inflammation in this model. Six LTNPs/ECs and 4 progressors were treated with PMPA and FTC daily for up to 24 weeks during chronic infection. Blood, lymph nodes and gut tissues were collected. Cell-associated viral DNA levels from purified CD4+ T cells in blood and gut lymphocytes were quantified by real-time PCR. The size of reservoirs was evaluated by quantitative coculture assays and real-time PCR. Immune cells restoration including IL-17+ subsets, proliferation and immune activation were monitored by flow cytometry. We found that plasma viral loads in all animals were suppressed and maintained to undetectable throughout ART. The levels of IL-17 expression in CD4 and CD8 T cells were not fully restored but slightly increased after ART. Immune activation significantly decreased. In conclusion, the ChRM nonhuman primate model is excellent for testing novel therapeutic interventions on TP and LTNPs/ECs for HIV eradication. Initiation of ART may be necessary for improvement of immune function for HIV/SIV infected LTNP/ECs.