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

Abstract

Background The aim of this large multicenter study was to determine variations in cerebrospinal fluid (CSF) HIV-RNA in different phases of untreated HIV-1 infection and its associations with plasma HIV-RNA and other biomarkers. Methods Treatment naïve adults with available CSF HIV-RNA quantification were included and divided into groups representing significant disease phases. Plasma HIV-RNA, CSF white blood cell count (CSF WBC), neopterin, and albumin ratio were included when available. Results 1.018 patients were included. CSF HIV-RNA was in median (IQR) 1.03 log10 (0.37–1.86) copies/mL lower than in plasma, and correlated with plasma HIV-RNA (r=0.44, p< 0.01), neopterin concentration in CSF (r=0.49, p< 0.01) and in serum (r=0.29, p< 0.01), CSF WBC (r=0.34, p< 0.01) and albumin ratio (r=0.25, p< 0.01). CSF HIV-RNA paralleled plasma HIV-RNA in all groups except neuroasymptomatic patients with advanced immunodeficiency (CD4 < 200) and patients with HIV-associated dementia (HAD) or opportunistic CNS infections. Patients with HAD had the highest CSF HIV-RNA (in median [IQR] 4.73 (3.84–5.35) log10 copies/mL). CSF > plasma discordance was found in 126 of 972 individuals (13%) and varied between groups, from 1% in primary HIV, 11% in neuroasymptomatic groups, up to 30% of patients with HAD. Conclusions Our study confirms previous smaller observations of variations in CSF HIV-RNA in different stages of HIV disease. Overall, CSF HIV-RNA was approximately 1 log10 copies/mL lower in CSF than in plasma, but CSF discordance was found in a substantial minority of subjects, most commonly in patients with HAD, indicating increasing CNS compartmentalization paralleling disease progression.

Neuroimmunology of CNS HIV Infection: A Narrative Review

“…The elements in these two compartments interact, and more particularly, systemic HIV disease serves as the foundation for the CNS complications in several aspects. It establishes the conditions of immunosuppression and immune activation that underlie CNS vulnerability ( 37 – 40 ), and, more directly, supplies the key elements of neuropathogenesis, including HIV invasion and major blood-derived cells involved in CNS immune-inflammatory reactions. However, while CNS virus-immune interactions partially echo those occurring systemically, there are important differences, with the CNS interactions being highly compartmentalized despite these systemic origins ( 36 ).…”

“…Among the viruses considered in this collection, HIV likely has the most complex and intimate interactions with the immune system and inflammatory responses, both outside (i.e., systemically) and within the CNS. In both systemic and CNS compartments these interactions change over the long course of chronic infection ( 36 , 37 ). Figure 1 diagrams these interactions, dividing the systemic (left) from CNS (right) processes.…”

Reversal of CSF HIV-1 Escape during Treatment of HIV-Associated Cryptococcal Meningitis in Botswana

“…The prevalence of CSF viral escape may differ between studies depending on the overall ART status of the participants. For instance, one study done on ART-naïve individuals reported a prevalence of 13% (126/972) [ 19 ] while another study reported 29% (12/42) cases of CSF viral escape in ART-experienced participants [ 20 ]. Furthermore, CSF viral escape may differ in acute versus chronic HIV infection.…”

Blood biomarkers for HIV infection with focus on neurologic complications—A review

“…HIV‐1 infects the central nervous system (CNS) shortly after transmission during primary infection 1 and can cause risk of HIV‐associated dementia during its advanced stage of the disease several years later, if left untreated 2 . In general, HIV is detected in the cerebrospinal fluid (CSF) in individuals with and without neurologic symptoms during all stages of infection, although the CSF the viral load is often higher in patients with HIV‐associated dementia or CNS opportunistic infections causing meningeal inflammation 3 …”

“…2 In general, HIV is detected in the cerebrospinal fluid (CSF) in individuals with and without neurologic symptoms during all stages of infection, although the CSF the viral load is often higher in patients with HIV-associated dementia or CNS opportunistic infections causing meningeal inflammation. 3 Chronic HIV infection causes progressive reduction in blood CD4+T-cell counts leading to immunosuppression and AIDS in a median of 10-11 years after primary infection. HIV-associated dementia and CNS opportunistic infections in general occur when CD4+ T cell counts fall below 200/mm 3 , that is, in patients with severe immunosuppression.…”