Early-treatment of HIV-infected patients favours the preservation and the development of HIV-specific B cells as well as TFH cells in the gastrointestinal mucosa

HIV-specific broadly neutralizing antibodies (nAbs) are highly-mutated immunoglobulins rarely found in HIV-infected patients. They result from the interaction between follicular helper T cells (Tfh) and B cells in germinal centers. We, recently, demonstrated the beneficial effects of early treatment on the preservation of intestinal lymphoid structure (ILS). Here, we analyzed the impact of treatment initiation either at the early phase of the primary infection (e-ART) or later during the chronic phase (l-ART) on blood and gastrointestinal mucosal (GM) human GP140-specific B-cells (B140) and on GM Tfh cells. e-ART patients displayed a higher frequency of GM B140 than l-ART patients whereas no difference was observed in the blood. B140 were significantly more represented in e-ART patients among resting memory B cells (73.60±2.16% vs. 50.03±9.77%, p=0.01), and less represented among naive (12.46 ± 4.65% vs. 37.87 ± 10.1%, p=0.04) and tissue-like memory B cells (0.58±0.23% vs. 3.69±0.95%, p=0.006) than l-ART patients. The frequency of Tfh cells was higher within e-ART than l-ART patients (11.43±1.96% vs. 3.30±0.71%, p=0.01), which strongly correlates with the frequency of B140 in GM (r=0.77, p=0.002). Our results demonstrate that early initiation of antiretroviral therapy preserves the Tfh cells present in ILS that maintain the HIV-specific B cells and could help to the development of nAbs.