Early initiation of antiretroviral treatment postSIV infection does not resolve lymphoid tissue activation

Abstract

Germinal center resident follicular helper T (TFH) cells in lymphoid follicles are a potential sanctuary for HIV/simian immunodeficiency virus (SIV) replication. But the dynamics of germinal centers upon early initiation of antiretroviral therapy (ART) and their potential role in the formation of viral sanctuaries post-SIV infection are not fully understood. Sequential lymph node biopsies (n = 10) were collected from SIVmac239-infected rhesus macaques before infection, at 5 weeks postinfection/pre-ART, 6 and 12 weeks following ART initiation. These tissues and cells were analyzed for frequencies of TFH cells and assignment of germinal center scores. Modest but significant increases in TFH cells and hyperplastic follicles with large germinal centers were noted during the acute phase of SIV infection (week 5/pre-ART). However, 6 weeks after ART initiation, substantial increases in germinal center TFH cells, germinal center B cells, hyperplastic follicles with large germinal centers, and abundant local IL-21 production were observed, whereas levels of SIV RNA and DNA of lymph nodes had decreased to barely detectable values along with barely detectable levels of SIV antibody-producing cells. An additional 6 weeks of ART did not appreciably decrease germinal center TFH or germinal center scores. Thus, although early ART rapidly controls SIV replication, it does not regulate early lymphoid activation, which may contribute to the seeding and magnitude of viral reservoirs.