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Multicenter Study
. 2016 Dec;22(6):852-860.
doi: 10.1007/s13365-016-0448-1. Epub 2016 May 18.

Discordant CSF/plasma HIV-1 RNA in patients with unexplained low-level viraemia

Sam Nightingale  1   2   3 , Anna Maria Geretti  4 , Apostolos Beloukas  4 , Martin Fisher  5 , Alan Winston  6 , Laura Else  7 , Mark Nelson  8 , Stephen Taylor  9 , Andrew Ustianowski  10 , Jonathan Ainsworth  11 , Richard Gilson  12 , Lewis Haddow  12 , Edmund Ong  13 , Victoria Watson  7 , Clifford Leen  14 , Jane Minton  15 , Frank Post  16 , Munir Pirmohamed  7 , Tom Solomon  4   17 , Saye Khoo  7   18
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Free PMC article
Multicenter Study

Discordant CSF/plasma HIV-1 RNA in patients with unexplained low-level viraemia

Sam Nightingale et al. J Neurovirol. 2016 Dec.
Free PMC article

Abstract

The central nervous system has been proposed as a sanctuary site where HIV can escape antiretroviral control and develop drug resistance. HIV-1 RNA can be at higher levels in CSF than plasma, termed CSF/plasma discordance. We aimed to examine whether discordance in CSF is associated with low level viraemia (LLV) in blood. In this MRC-funded multicentre study, we prospectively recruited patients with LLV, defined as one or more episode of unexplained plasma HIV-1 RNA within 12 months, and undertook CSF examination. Separately, we prospectively collected CSF from patients undergoing lumbar puncture for a clinical indication. Patients with durable suppression of viraemia and no evidence of CNS infection were identified as controls from this group. Factors associated with CSF/plasma HIV-1 discordance overall were examined. One hundred fifty-three patients were recruited across 13 sites; 40 with LLV and 113 undergoing clinical lumbar puncture. Seven of the 40 (18 %) patients with LLV had CSF/plasma discordance, which was significantly more than 0/43 (0 %) with durable suppression in blood from the clinical group (p = 0.005). Resistance associated mutations were shown in six CSF samples from discordant patients with LLV (one had insufficient sample for testing), which affected antiretroviral therapy at sampling in five. Overall discordance was present in 20/153 (13 %) and was associated with nadir CD4 but not antiretroviral concentrations in plasma or CSF. CSF/plasma discordance is observed in patients with LLV and is associated with antiretroviral resistance associated mutations in CSF. The implications for clinical practice require further investigation.

Keywords: Antiretroviral agents; Central nervous system; Cerebrospinal fluid; Drug resistance; HIV; Viral.

Conflict of interest statement

Compliance with ethical standards Written informed consent was obtained from all participants. The study was approved by the North Wales Research Ethics Committee (Central and East). Funding SN is a MRC Clinical Training Fellow supported by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the Medical Research Council (grant number G1000417/94909), ICON, GlaxoSmithKline, AstraZeneca and the Medicines Evaluation Unit. SN also received a research award to support this work from the British HIV Association. Conflicts of interest The authors declare that they have no competing interest.

Figures

Fig. 1
Fig. 1
CSF HIV-1 RNA in 40 patients with intermittent or persistent low-level plasma HIV-1 RNA detection in the last year versus 43 patients from a clinical cohort with durable HIV-1 RNA suppression in the last year. Filled circles represent discordant samples
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