HIV-1 persistence in lymph node T follicular helper cells (TFH) is mitigated by functional virus-specific T cell responses during hyperacute-treated HIV-1 infection

Abstract HIV persistence in tissue sites despite ART is a major barrier to HIV cure. Detailed studies of HIV infected cells and immune responses in native lymph node (LN) tissue environment is critical for gaining insight into immune mechanisms impacting HIV persistence and clearance in tissue sanctuary sites. We compared HIV persistence and HIV-specific T cell responses in LN biopsies obtained from 14 individuals who initiated therapy in Fiebig stages I/II, 5 persons treated (Tx) in Fiebig stages III-V and 17 late Tx individuals who initiated ART in Fiebig VI and beyond. Using multicolor immunofluorescence staining and in situ hybridization, HIV RNA and/or protein was detected in 12 of 14 Fiebig I/II Tx persons who were on suppressive therapy for 1 to 55 months, while all late Tx persons had persistent antigens. CXCR3+T follicular helper T cells harbored the greatest amounts of gag mRNA transcripts. Notably, HIV-specific CD8+ T cells responses associated with lower HIV antigen burden in LNs, suggesting that these responses may contribute to HIV suppression in LNs during therapy. These results reveal HIV persistence despite the initiation of ART in hyperacute infection and highlight the contribution of virus-specific responses to HIV suppression in tissue sanctuaries during suppressive ART.