Herpes zoster in HIV-1 infection: The role of CSF pleocytosis in secondary CSF escape and discordance

Abstract

HIV cerebrospinal fluid (CSF) escape is defined by a concentration of HIV-1 RNA in CSF above the lower limit of quantification of the employed assay and equal to or greater than the plasma HIV-1 RNA level in the presence of treatment-related plasma viral suppression, while CSF discordance is similarly defined by equal or higher CSF than plasma HIV-1 RNA in untreated individuals. During secondary CSF escape or discordance, disproportionate CSF HIV-1 RNA develops in relation to another infection in addition to HIV-1. We performed a retrospective review of people living with HIV receiving clinical care at Sahlgrenska Infectious Diseases Clinic in Gothenburg, Sweden who developed uncomplicated herpes zoster (HZ) and underwent a research lumbar puncture (LP) within the ensuing 150 days. Based on treatment status and the relationship between CSF and plasma HIV-1 RNA concentrations, they were divided into 4 groups: i) antiretroviral treated with CSF escape (N = 4), ii) treated without CSF escape (N = 5), iii) untreated with CSF discordance (N = 8), and iv) untreated without CSF discordance (N = 8). We augmented these with two additional cases of secondary CSF escape related to neuroborreliosis and HSV-2 encephalitis and analyzed these two non-HZ cases for factors contributing to CSF HIV-1 RNA concentrations. HIV-1 CSF escape and discordance were associated with higher CSF white blood cell (WBC) counts than their non-escape (P = 0.0087) and non-discordant (P = 0.0017) counterparts, and the CSF WBC counts correlated with the CSF HIV-1 RNA levels in both the treated (P = 0.0047) and untreated (P = 0.002) group pairs. Moreover, the CSF WBC counts correlated with the CSF:plasma HIV-1 RNA ratios of the entire group of 27 subjects (P = <0.0001) indicating a strong effect of the CSF WBC count on the relation of the CSF to plasma HIV-1 RNA concentrations across the entire sample set. The inflammatory response to HZ and its augmenting effect on CSF HIV-1 RNA was found up to 5 months after the HZ outbreak in the cross-sectional sample and, was present for one year after HZ in one individual followed

Cerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study

“…This might either be a reflection of facilitated penetration of peripheral virions into the CNS or that blood brain barrier impairment leads to an increased inflammatory response resulting in higher levels of locally replicated virus [ 28 ]. CSF HIV-RNA in the CNS OI group was also weakly associated with CSF pleocytosis, a finding previously observed in smaller studies [ 29 , 30 ] and in other CNS coinfections such as neuroborreliosis and herpes zoster [ 20 , 31 ]. By contrast, PML, an opportunistic CNS infection associated with only minor CNS inflammation, was not associated with an increased CSF viral burden.…”

“…CSF HIV-RNA was characteristically lower than plasma HIV-RNA, with a median (IQR) difference of 1.03 (0.37–1.86) log 10 copies/mL ( Table 1 and Figure 1 ). CSF HIV-RNA discordance, defined as CSF≥ plasma HIV-RNA in untreated individuals [ 20 ] (ie, a plasma:CSF ratio ≤ 0) was found in 126 of 972 patients (13%) with a wide variation between the various groups. Figure 2 shows the proportion of patients with CSF HIV-RNA > plasma HIV-RNA by groups.…”

Neuroimmunology of CNS HIV Infection: A Narrative Review

“…Secondary escape entails a disproportional increase in CSF HIV RNA in association with another CNS inflammatory process (usually another CNS infection) that provokes local HIV replication through recruitment of activated lymphocytes. Treatment of the provoking infection leads to reduction of the CSF HIV RNA elevation ( 79 ).…”

Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression

“…Indeed, even when assessed by very sensitive assays, HIV-1 RNA detection is characteristically less frequent and measured at lower levels in CSF than plasma [ 20 , 45 , 46 ]. However, there are also notable exceptions to CNS virological efficacy: CSF HIV-1 escape in which CSF HIV-1 RNA levels exceed those of plasma, either with clinical impact ( neurosymptomatic CSF escape ) [ 47 , 48 ] or not ( asymptomatic CSF escape ) [ 49 ], or in the presence of another CNS infection ( secondary CSF escape ) [ 50 ]. While these escape settings were not included in this study, their inflammatory profiles warrant further study [ 51 ].…”