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.
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.
['Joseph|Sarah B|SB|', 'Kincer|Laura P|LP|', 'Bowman|Natalie M|NM|', 'Evans|Chris|C|', 'Vinikoor|Michael J|MJ|', 'Lippincott|Christopher K|CK|', 'Gisslén|Magnus|M|', 'Spudich|Serena|S|', 'Menezes|Prema|P|', 'Robertson|Kevin|K|', 'Archin|Nancie|N|', 'Kashuba|Angela|A|', 'Eron|Joseph J|JJ|', 'Price|Richard W|RW|', 'Swanstrom|Ronald|R|']
D000328:Adult D044966:Anti-Retroviral Agents D058070:Asymptomatic Diseases D002490:Central Nervous System D002555:Cerebrospinal Fluid D015331:Cohort Studies D003430:Cross-Sectional Studies D024882:Drug Resistance, Viral D005260:Female D015658:HIV Infections D015497:HIV-1 D006801:Humans D008137:Longitudinal Studies D008297:Male D008875:Middle Aged D010949:Plasma D012367:RNA, Viral D013601:T-Lymphocytes D019562:Viral Load
CNS CSF escape persistence drug resistance HIV reservoirs