Early initiation of antiretroviral therapy (ART) in acute HIV infection (AHI) could help preempt evasion and damage of the immune system by HIV. Use of the integrase inhibitor Dolutegravir (DTG) and 2NRTIs is the new standard regimen. However, the influence of these drugs on the recovery of immune cells in blood and lymph node (LN) tissue has not been well studied. To address this, we assessed differences in B cell populations in Thai participants randomized to switch from 2NRTI+EFV to 2NRTI+DTG.
Cryopreserved peripheral blood mononuclear cells (PBMCs) and lymph node mononuclear cells (LNMCs) from 27 AHI treated Thai participants enrolled in the RV254 cohort were analyzed. Participants were grouped based on ART regimen: those randomized to switch from 2NRTI+EFV to 2NRTI+DTG (n=13; 6-22 mos EFV followed by 9-20 mos DTG) and those who remained on 3TC/TDF/EFV (n=14; range 6-22 mos). Eighteen uninfected individuals (HIV–) enrolled in RV304 were included for comparison. B cells were characterized by flow cytometry.
The frequencies of CD19+ B cells were significantly decreased in PBMCs but not LNMCs of 2NRTI+EFV treated compared to HIV– participants (p<0.05), but were recovered in those who switched to DTG. The frequencies of resting memory B cells (RM; CD21+CD27+IgG+CD20+) were significantly decreased in both PBMCs and LNMCs of the 2NRTI+EFV group (Fig 1a), whereas the frequencies of tissue-like memory B cells (TLM) were significantly increased compared to HIV– participants (p<0.05; Fig 1b). 2NRTI+DTG treated participants had recovered frequencies of RM B cells, but lower frequencies of TLM and activated memory B cells (AM) compared to HIV– participants and non-switched EFV-treated participants (p<0.05; Fig 1c).
Our data show that switching from 2NRTI+EFV to 2NRTI+DTG could aid in recovery of B cell populations in the blood and LN, although the number of LNMC samples in the 2NRTI+DTG group in the present study limits definitive conclusions for this compartment. We observed higher frequencies of B cells and RM B cells in both PBMCs and LNMCs after switching from 2NRTI+EFV to 2NRTI+DTG. Further, 2NRTI+DTG treated participants had fewer AM and TLM B cells, the latter of which have an exhausted phenotype. These data suggest that switching from EFV to DTG may be beneficial to limit activation and exhaustion in the B cell compartment of participants who initiated treatment in AHI.