HIV lymphoid tissue fibrosis occurs in the earliest stages of acute HIV infection and is associated with macrophage-derived TGF-β

HIV infection is associated with lymphatic tissue damage caused by collagen deposition in the fibroblastic reticular cell network (FRCn) of the parafollicular T cell zone (TZ), which leads to impaired antigen presentation, T cell depletion, and reduced antibody formation. In treated chronic HIV infection, damage persists despite antiretroviral therapy (ART), but it is not known if very early initiation of ART could limit damage and preserve immune function. We studied participants in the Thai RV254 acute infection cohort and found significant collagen deposition in the FRCn even in the earliest Fiebig stage 1 acute infection. The amount of TZ collagen correlates with the frequency of TGF-β+ macrophages which, in turn, correlates with the frequency of HIV RNA-producing cells. We conclude that immediate initiation of ART may have limited impact in preventing or reversing collagen accumulation in LNs.