HIV-1 RNA Detected in the CNS after Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells.

• 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.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 sufficiently high to permit analysis, viral populations were genetically and phenotypically characterized over multiple time points.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 (i.e. CSF escape). We generated viral envelope sequences from CSF of three 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 viral lineage present in the blood prior to viral suppression and enriched for after ART. Two participants (one suppressed and one not) had transient CSF escape populations that were R5 T cell-tropic with little genetic diversity.Extensive analysis of viral populations in one 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 two 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, but that CSF escape is not exclusively produced by a replicating CNS reservoir.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

Nyckelord

CNS

CSF escape

HIV reservoirs

drug resistance

persistence

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)