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

被引:65
作者
Joseph, Sarah B. [1 ]
Kincer, Laura P. [1 ]
Bowman, Natalie M. [2 ]
Evans, Chris [2 ]
Vinikoor, Michael J. [2 ]
Lippincott, Christopher K. [3 ]
Gisslen, Magnus [4 ]
Spudich, Serena [5 ]
Menezes, Prema [2 ,6 ]
Robertson, Kevin [7 ]
Arching, Nancie [2 ]
Kashuba, Angela [6 ,8 ]
Eron, Joseph J. [2 ,6 ]
Price, Richard W. [9 ]
Swanstrom, Ronald [6 ,10 ]
机构
[1] Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Sch Med, Div Infect Dis, Chapel Hill, NC 27599 USA
[3] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA
[4] Univ Gothenburg, Dept Infect Dis, Sahlgrenska Acad, Gothenburg, Sweden
[5] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA
[6] Univ N Carolina, Ctr AIDS Res, Chapel Hill, NC 27599 USA
[7] Univ N Carolina, Dept Neurol, Chapel Hill, NC 27599 USA
[8] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA
[9] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA
[10] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27515 USA
基金
美国国家卫生研究院;
关键词
CNS; CSF escape; HIV reservoirs; drug resistance; persistence; HIV-1; DRUG-RESISTANCE; CEREBROSPINAL-FLUID; MACROPHAGE TROPISM; ENTRY PHENOTYPES; ESCAPE; BRAIN; QUANTIFICATION; DEPENDENCE; ENVELOPES; COPIES/ML;
D O I
10.1093/cid/ciy1066
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1345 / 1352
页数:8
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