The symptomatology of cerebrospinal fluid HIV RNA escape: a large case-series

Abstract

Objective: To characterize the clinical, laboratory and radiological characteristics of persons with HIV (PWH) presenting with cerebrospinal fluid (CSF) HIV RNA escape.Design: Retrospective case review of PWH presenting with symptomatic CSF HIV RNA escape at seven tertiary HIV clinical sites in the United Kingdom and Italy.Method: PWH with symptomatic CSF HIV RNA escape episodes were identified and data obtained from medical records. CSF HIV RNA escape was defined as quantifiable CSF HIV RNA in unquantifiable plasma HIV RNA or CSF HIV RNA greater than plasma HIV RNA in cases where plasma HIV RNA was quantifiable. The onset of clinical symptoms was classified as acute (<2 weeks-6 months), or chronic (>6 months) and differences in presentation in those with CSF HIV RNA below and above 1000 copies/ ml determined. Results:We identified 106 PWH with CSF HIV RNA escape (65 male); 68 (64%) PWH had acute presentations and 38 (36%) had chronic presentations. Cognitive decline (n ¼ 54; 50.9%), confusion (n ¼ 20; 18.9%) and headache (n ¼ 28; 26.4%) were the most common presentations, with cognitive decline being more common in PWH who presented chronically compared with PWH who presented acutely (73.7% vs. 35.3%, P ¼ 0.0002). Sixty PWH had CSF HIV RNA at least 1000 copies/ml and presented more frequently with confusion (n ¼ 15/60; 25.0%) compared with PWH with CSF HIV RNA less than 1000 copies/ml at presentation (n ¼ 5/46; 10.9%; P ¼ 0.03).

The Presence of Resistance-associated Mutations in Reverse Transcriptase Gene is Associated with Cerebrospinal Fluid HIV-1 Escape: a multicentric retrospective analysis

“…This entity is known as CSF viral escape (CVE) and has been described in 2-20% of patients in several cohorts worldwide [2][3][4][5][6] . Neurologically symptomatic CVE is a rare clinical syndrome that has been often described in the presence of CSF drug resistance associated mutations (RAMs) in HIV genes [7][8][9] . On the contrary, asymptomatic CVE has been more commonly detected in clinical studies of asymptomatic participants undergoing lumbar puncture (LP), where selection bias may exist 8,10,11 .…”

“…Neurologically symptomatic CVE is a rare clinical syndrome that has been often described in the presence of CSF drug resistance associated mutations (RAMs) in HIV genes [7][8][9] . On the contrary, asymptomatic CVE has been more commonly detected in clinical studies of asymptomatic participants undergoing lumbar puncture (LP), where selection bias may exist 8,10,11 . The long-term implications of CVE remain unclear: longitudinally, patients with detectable CSF HIV RNA may have higher inflammation but no emergence of neurological symptoms 11 .…”

Biotypes of HIV-associated neurocognitive disorders based on viral and immune pathogenesis

“…Patients with symptomatic viral escape have a wide spectrum of symptoms including headache, tremors, cognitive impairment, confusion, focal neurologic deficits, and seizures [25,36,37]. These symptoms most often occur months to years after being stable on ART [22,25].…”

The presence of resistance‐associated mutations in reverse transcriptase gene is associated with cerebrospinal fluid HIV‐1 escape: A multicentric retrospective analysis

“…[7][8][9] On the contrary, asymptomatic CVE has been more commonly detected in clinical studies of asymptomatic participants undergoing lumbar puncture (LP), where selection bias may exist. 8,10,11 The long-term implications of CVE remain unclear: longitudinally, patients with detectable CSF HIV RNA may have higher inflammation but no emergence of neurological symptoms. 11 Several risk factors for CVE have been reported: the duration of HIV infection, suboptimal adherence, low CD4+ T-cell count nadir, reduced central nervous system (CNS) penetration of antiretrovirals (ARVs), and the use of specific ARVs.…”