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

BACKGROUND

The aim of this large multicenter study was to determine variations in cerebrospinal fluid (CSF) HIV-RNA in different phases of untreated human immunodeficiency virus type 1 (HIV-1) infection and its associations with plasma HIV-RNA and other biomarkers.

METHODS

Treatment naive 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 (WBC), neopterin, and albumin ratio were included when available.

RESULTS

In total, 1018 patients were included. CSF HIV-RNA was in median (interquartile range [IQR]) 1.03 log10 (0.37-1.86) copies/mL lower than in plasma, and correlated with plasma HIV-RNA (r = 0.44, P < .01), neopterin concentration in CSF (r = 0.49, P < .01) and in serum (r = 0.29, P < .01), CSF WBC (r = 0.34, P < .01) and albumin ratio (r = 0.25, P < .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 central nervous system (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.

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

Déclaration de conflit d'intérêts

Potential conflicts of interest. A. A. reports consultation fees received personally from Gilead, ViiV Healthcare, Janssen Cilag, Merck, and GlaxoSmithKline; payment or honoraria from Gilead, ViiV Healthcare, Janssen Cilag, and Merck personally received; and support for attending meetings from ViiV Healthcare and AbbVie. C. P. reports personal fees for case presentation from GILEAD; personal fees for travel grant from GILEAD; and personal fees for Advisory Board from JANSEEN-CILAG. A. C. reports grants or contracts from VIIV and GILEAD outside of the submitted work; consulting fees from VIIV, GILEAD, J&J, MSD, and INSMED; and payment or honoraria from VIIV, GILEAD, J&J, MSD, and INSMED. A. W. reports grants from ViiV Healthcare, Gilead Sciences, Janssen, and MSD to Imperial College London on their behalf; lecture fees from ViiV Healthcare, Gilead Sciences, Janssen, and MSD; and sits on DSMBs of academic studies. C. O. reports payment or honoraria from ViiV, Neola Pharma, and MSD; serving on MSD advisory board and Gilead advisory board; and being a Member of European AIDS Clinical Society (EACS) Governing board and Member of EuroSIDA Steering Community. L. H. reports participation on a Data Safety Monitoring Board or Advisory Board for Borrelia vaccine Pfizer. M. G. reports Swedish State Support for Clinical Research (grant number ALFGBG- -717531) to the institution for the present article. R. W. P. reports support for the present article from R01 NS094067 and R01 NS094067-05S1 (R. W. P. principal investigator [PI]), R21MH096619 (R. W. P. PI), P01 MH094177 (Ronald Swanstrom, PI, University of North Carolina, Chapel Hill) to University of California at San Francisco (UCSF). S. S. reports grant award payments made to the institution from the NIH/NIMH for the present article. P. C. reports grants to the institution from Gilead, UCSF (NIH subcontracts), ISS, Italy, and ViiV Healthcare for the present article; payment or honoraria from Gilead, ViiV Healthcare, and Janssen; and support for attending meetings and/or travel from Gilead, ViiV Healthcare, and Janssen. G. U. reports support from Swedish government and county councils (Receiver of funding according to the ALF-agreement (ALFGBG-70150); personal payments and payments to institution). B. B. reports grant funding paid to their institution from National Health and Medical Research Australia and National Institutes of Health. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.