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.

Cerebrospinal fluid compartmentalization of HIV-1 and correlation with plasma viral load and blood–brain barrier damage

Bavaro D. F.;CALAMO, ANGELA;Lepore L.;Fabrizio C.;Saracino A.;Angarano G.;Monno L.
2019

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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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/237962
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