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

PurposeWe 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 designWe 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.ResultsOverall, 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.ConclusionsOur 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.