Effect of antiretroviral therapy on HIV reservoirs in elite controllers

Abstract

Elite controllers suppress human immunodeficiency virus (HIV) viremia to below the limit of detection in the absence of antiretroviral therapy (ART). However, precise frequencies of CD4(+) T cells carrying replication-competent HIV and/or the dynamics of the infectious viral reservoirs in response to initiation and discontinuation of ART in elite controllers are unknown. We show that the size of the pool of CD4(+) T cells harboring infectious HIV diminished significantly after initiation of ART and rebounded to baseline upon cessation of therapy. Our data provide compelling evidence that persistent viral replication occurs in untreated elite controllers even in the absence of detectable plasma viremia.

Keywords: antiretroviral therapy; elite controllers; human immunodeficiency virus; viral reservoirs.

Figure 1.

Levels of CD4⁺ and CD8⁺ T cells (A), plasma viremia (B), CD4⁺ T cells carrying replication-competent human immunodeficiency virus (HIV) (C), and HIV-specific CD8⁺ T cells (D) in infected study subjects after initiation and discontinuation of antiretroviral therapy (ART). B, Plasma viremia was determined using Cobas Ampliprep/Cobas Taqman HIV-1 Test Version 2.0 (Roche Diagnostics) with a detection limit of 20 copies/mL plasma. C, The open squares represent values below the limit of detection. When cocultures were negative, the frequency was estimated to be lower than the number calculated based on the assumption that 1 well containing 10 million cells would be culture-positive by p24 enzyme-linked immunosorbent assay. D, Peripheral blood mononuclear cells (PBMCs) were incubated with overlapping 15-mer HIV Gag peptides for 6 hours, and the frequency of CD8⁺CD45RO⁺CD27⁺ T cells expressing intracellular interferon γ (INF-γ), interleukin 2 (IL-2), macrophage inflammatory protein 1ß (MIP-1ß), and tumor necrosis factor α (TNF-α) was determined by flow cytometry. The shaded area represents the period of ART.