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

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.

Diffuse White Matter Signal Abnormalities on Magnetic Resonance Imaging Are Associated With Human Immunodeficiency Virus Type 1 Viral Escape in the Central Nervous System Among Patients With Neurological Symptoms

“…The 15% prevalence of CSF discordance is similar to the 12% reported by Nightingale et al [2] and the 21% found by Rawson et al in London [1]. The 6% prevalence of CSF escape agrees with the 0–15% quoted in a systematic review by Pérez Valero et al [5].…”

Incidence of symptomatic CSF viral escape in HIV infected patients receiving atazanavir/ritonavir (ATV/r)-containing ART: a tertiary care cohort in western India

“…In our clinic, 23 (88.5%) of the CSFVE patients were on regimens that had CPE score of ≤ 7, a possible risk factor for CSFVE, and all except one patient were receiving TDF/FTC backbone. Published literature so far reported CSFVE in patients receiving different ART combinations with different CPE score (Nightingale et al 2016) To our knowledge, this is the first study looking at the incidence of symptomatic CSF escape in patients receiving only ATV/r-containing ART in clinical practice. Atazanavir containing-regimen is recommended second-line ART in India after NNRTI containing regimen failure.…”

“…Despite this unique property of NRTIs, TDF with the lowest CPE score of 1 among NRTIs can have a possible association with risk of CSFVE. Study from Cusini et al reported all four patients diagnosed with CSFVE were receiving TDF/FTC backbone, and none of the patients receiving AZT ( n = 39) or ABC ( n = 18) developed CSFVE at any given time in the study while in another study out of the 20 patients described, 12 were receiving TDF, 2 were not received any NRTI and 2 each were receiving single NRTI, AZT/3TC, and ABC/3TC NRTI backbone (Cusini et al 2013; Nightingale et al 2016). In our study, also none of the patients receiving AZT/3TC or ABC/3TC developed symptomatic CSFVE, suggests a possible association of the use of TDF with the risk of getting CSFVE.…”

Utilidad de la cuantificación de carga viral de VIH en líquido cefalorraquídeo, a propósito de un caso

“…Se ha denominado discordancia entre plasma y LCR cuando existen diferencias entre los niveles de ARN viral de VIH entre estos compartimentos; cuando es mayor en LCR, puede resultar en la detección de variantes VIH resistentes a fármacos 8 . En la mayoría de los estudios se considera que existe una discordancia en los niveles de CV si es 0,5 log mayor en el LCR que en el plasma 8,9 .…”

“…Se encontró discordancia entre el LCR y plasma en 18% de pacientes (7 de 40). En el grupo control, de los que tenían CV en plasma suprimida, ninguno tuvo discordancia (0 de 43 pacientes) 9 . Al realizar la genotipificación viral, se Caso Clínico demostraron mutaciones que conferían resistencia a la TARV, llevando a un cambio de la TARV en cinco pacientes.…”