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

Abstract

This single-center study attempts to quantify the incidence of symptomatic CSF viral escape (CSFVE) in patients receiving atazanavir/r (ATV/r)-containing regimen. We performed a retrospective analysis of patients receiving ATV/r-containing ART who were diagnosed with symptomatic CSFVE from August 2012 to January 2017. Primary objective was to assess the incidence of symptomatic CSFVE in patients receiving ATV/r-containing ART in clinical practice. Incidence rates were calculated by dividing the number of patients who experienced CSFVE by the number of person-months at risk and summarized as per 10,000 (ten thousand) person-months at risk. Nine hundred thirty-three patients receiving ATV/r containing ART with a total of 36,068 person-months of follow-up were included. Incidence rate of symptomatic CSFVE was 4.4 per 10,000 person-months (95% CI 2.7 to 7.2). The incidence of CSFVE was 9.5 per 10,000 person-months (95% CI 5.7 to 15.7) when the nadir CD4 count was ≤ 200 compared to 0.49 (95% CI 0.07 to 3.5) with a nadir CD4 count > 200 (IRR 19.1 (95% CI 2.93 to 802.8), p < 0.0001). Nadir CD4 count ≤ 200 was associated with substantially increased risk of symptomatic CSFVE, further strengthening efforts to diagnose and treat patients early in disease.

Differences in human immunodeficiency virus-1C viral load and drug resistance mutation between plasma and cerebrospinal fluid in patients with human immunodeficiency virus-associated cryptococcal meningitis in Botswana

“…[ 26 – 28 ] If these participants were previously exposed to PIs then occurrence of these mutations solely in the CSF compartment would be attributable to low CNS penetration effectiveness of PIs via the BBB. [ 6 , 29 , 30 ] In all these participants with HIV-1 DRM discordance, there was no evidence of viral escape as a result of present DRMs. One patient harboured HIV-1 strain with extensive DRMs and high HIV-1 VL in both CSF and plasma (patient ID:1736, Table 3 ).…”

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

“…This was coherently defined in a report of 11 treated patients presenting with a variety of neurological symptoms and signs who exhibited higher CSF than plasma HIV-1 RNA concentrations [18]. Additional reports preceded [19] and have followed [20][21][22][23][24][25][26][27][28][29], and this condition is now termed neurosymptomatic CSF escape based on the clinical presentation of neurological deficits in the presence of detectable CSF HIV-1 RNA despite systemic viral suppression [15,17,30]. This is clinically the most important type of CSF escape and can present with major neurological deficits and imaging abnormalities [20].…”

“…HIV-1 causality is also supported by the frequent therapeutic benefit of treatment modification on neurological symptoms and signs [18,20,29]. Most, but not all, of these individuals exhibit inadequate CNS treatment regimens related to drug resistance of the CNS virus population or to insufficient 'penetration' of the full combination of drugs into the CNS compartment by virtue of their pharmacological properties-or, frequently, to a combination of these two factors [18,20,27]. It may also involve important immunopathology with some features in common with the immune reconstitution inflammatory syndrome (IRIS) [32].…”

Symptomatic HIV CNS viral escape among patients on effective cART

“…Also TDF causes reduction in the area under the curve concentrations and Cmin of Atazanavir when used in combination (Taburet et al, 2004). The combination may therefore be especially vulnerable regarding the CNS in combination with suboptimal adherence and resistance (Patel et al, 2018). Hence, it is likely that the factors compounding the poor CNS penetration of Atazanavir to induce viral escape are multifactorial and synergistic.…”