Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells. (18th December 2018)

• Record Type: Journal Article
• Authors: Joseph, Sarah B; Kincer, Laura P; Bowman, Natalie M; Evans, Chris; Vinikoor, Michael J; Lippincott, Christopher K; Gisslén, Magnus; Spudich, Serena; Menezes, Prema; Robertson, Kevin; Archin, Nancie; Kashuba, Angela; Eron, Joseph J; Price, Richard W; Swanstrom, Ronald
• Is Part Of: Clinical infectious diseases. Volume 69:Number 8(2019)
• Page Start: 1345
• Page End: 1352
• Publication Date: 2018-12-18
• Subjects: CNS -- CSF escape -- HIV reservoirs -- drug resistance -- persistence; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciy1066
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: Human immunodeficiency virus type 1 (HIV-1) populations are detected in cerebrospinal fluid (CSF) of some people on suppressive antiretroviral therapy (ART). Detailed analysis of these populations may reveal whether they are produced by central nervous system (CNS) reservoirs. Methods: We performed a study of 101 asymptomatic participants on stable ART. HIV-1 RNA concentrations were cross-sectionally measured in CSF and plasma. In participants with CSF HIV-1 RNA concentrations sufficient for analysis, viral populations were genetically and phenotypically characterized over multiple time points. Results: For 6% of participants (6 of 101), the concentration of HIV-1 RNA in their CSF was ≥0.5 log copies/mL above that of plasma (ie, CSF escape). We generated viral envelope sequences from CSF of 3 participants. One had a persistent CSF escape population that was macrophage-tropic, partially drug resistant, genetically diverse, and closely related to a minor macrophage-tropic lineage present in the blood prior to viral suppression and enriched for after ART. Two participants (1 suppressed and 1 not) had transient CSF escape populations that were R5 T cell-tropic with little genetic diversity. Conclusions: Extensive analysis of viral populations in 1 participant revealed that CSF escape was from a persistently replicating population, likely in macrophages/microglia, present in the CNS over 3 years of ART. CSF escape in 2 other participants was likely produced by trafficking and transient expansion of infected T cells in the CNS. Our results show that CNS reservoirs can persist during ART and that CSF escape is not exclusively produced by replicating CNS reservoirs. Abstract : Analyses of human immunodeficiency virus type-1 in the cerebrospinal fluid of antiretroviral therapy (ART)-treated, virologically-suppressed people suggest these populations are produced by replicating central nervous system (CNS) reservoirs present during long-term ART or infected T cells trafficking into the CNS.