Early initiation of antiretroviral treatment postSIV infection does not resolve lymphoid tissue activation. (24th August 2017)

• Record Type: Journal Article
• Authors: Hong, Jung J.; Silveira, Eduardo L. di Volpe; Amancha, Praveen K.; Byrareddy, Siddappa N.; Gumber, Sanjeev; Chang, Kyu-Tae; Ansari, Aftab A.; Villinger, Francois
• Is Part Of: AIDS. Volume 31:Number 13(2017)
• Publication Date: 2017-08-24
• Subjects: antiretroviral drugs -- germinal center -- follicular helper T cell; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001576
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Objective: 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. Design: 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. Results: 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. Conclusion: 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. Abstract : Supplemental Digital Content is available in the text