Abstract
Purpose
We aimed to evaluate HIV-1 compartmentalization between the cerebrospinal fluid (CSF) and plasma and investigate as to which extent HIV-1 strains in CSF differ from those in blood and whether a correlation with either plasma viral load (pVL) or an altered blood–brain barrier (BBB) does exist.
Study design
We retrospectively evaluated paired CSF/blood samples collected from 86 HIV+ patients. HIV-RNA quantification, pol (PR/RT), and V3 sequencing were performed. HIV coreceptor tropism (CRT) was inferred (g2p, false-positive rate 10%, FPR). Data of standard CSF analysis were also reviewed; an altered CSF/plasma albumin ratio signified BBB damage. Neurological abnormalities (NA) were recorded.
Results
Overall, 32% of patients had a CSF/plasma HIV-RNA ratio > 1 (discordance); 3% of patients had detectable CSF HIV-RNA despite suppressed pVL (escape). Discordance was more frequent in ART-treated patients (p < 0.001) and in patients with NA (p = 0.016), but was independent of BBB damage (p = 0.65) and AIDS diagnosis (p = 0.96). Finally, CSF/plasma discordance was significantly more frequent (p < 0.0001) in patients with lower pVL values (< 10.000 copies/ml). Env divergence > 10% was found in 44% of sequences and was associated with ART (p = 0.008) and NA (p = 0.037). Overall, 24% of patients had a discordant CSF/blood CRT. A 100% nucleotide identity was observed in only 7.3% of pol sequences; notably, 10% of patients had resistance-associated mutations in CSF, but not in blood.
Conclusions
Our data confirm an independent replication and evolution of HIV within the CSF. A number of factors either hinder or contribute to the compartmentalization of HIV.
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Acknowledgements
The authors would like to thank all patients who participated in the study. The authors also wish to thank Mrs Paulene Butts for her assistance in manuscript preparation.
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The research did not require approval from the ethics committee according to the Italian law since it was performed as an observational retrospective study in the context of normal clinical routines.
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Bavaro, D.F., Calamo, A., Lepore, L. et al. Cerebrospinal fluid compartmentalization of HIV-1 and correlation with plasma viral load and blood–brain barrier damage. Infection 47, 441–446 (2019). https://doi.org/10.1007/s15010-019-01268-8
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DOI: https://doi.org/10.1007/s15010-019-01268-8