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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
- Source :
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol 69, iss 8
- Publication Year :
- 2018
- Publisher :
- Oxford University Press (OUP), 2018.
-
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.
- Subjects :
- Central Nervous System
Male
0301 basic medicine
T-Lymphocytes
Drug Resistance
HIV Infections
Drug resistance
Medical and Health Sciences
CSF escape
Cohort Studies
Plasma
0302 clinical medicine
Cerebrospinal fluid
2.2 Factors relating to the physical environment
Viral
Longitudinal Studies
030212 general & internal medicine
Aetiology
Articles and Commentaries
Cerebrospinal Fluid
education.field_of_study
Microglia
persistence
Viral Load
Middle Aged
Biological Sciences
Mental Health
Infectious Diseases
medicine.anatomical_structure
Anti-Retroviral Agents
RNA, Viral
HIV/AIDS
Female
CNS
Infection
Adult
Microbiology (medical)
Lineage (genetic)
030106 microbiology
Population
Central nervous system
HIV reservoirs
Microbiology
03 medical and health sciences
Viral envelope
Drug Resistance, Viral
medicine
Humans
education
business.industry
Neurosciences
RNA
Virology
Cross-Sectional Studies
Asymptomatic Diseases
HIV-1
business
Subjects
Details
- ISSN :
- 15376591 and 10584838
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- Clinical Infectious Diseases
- Accession number :
- edsair.doi.dedup.....58bc74088551d1feb6f3d18c3b962090