Single-copy assay quantification of HIV-1 RNA in paired cerebrospinal fluid and plasma samples from elite controllers

Abstract

Elite controllers (ECs) are a rare subset of HIV-1 infected individuals who maintain HIV-1 RNA concentrations in plasma below the lower limit of quantification of clinical assays (<20–50 copies/mL) in the absence of antiretroviral therapy. Here we examine to what extent ECs also control infection of the central nervous system (CNS). We analyzed paired cerebrospinal fluid (CSF) and plasma samples using a highly sensitive assay for HIV-1 RNA quantification. We analyzed 28 CSF samples and 27 concurrent plasma samples from 14 ECs with the highly sensitive single-copy assay (SCA) that allows for HIV-1 RNA quantification down to less than 1 copy of HIV-1 RNA/mL. Three samples were excluded because of internal standard failure. HIV-1 RNA was detected in only 5/26 CSF samples compared to 14/26 plasma samples (P=0.02), with a median of 0.2 (range 0.1–6) copies/mL in CSF compared to 0.8 (range 0.1–189) in plasma (P<0.0001). HIV-1 RNA could not be detected in CSF in most ECs using the highly sensitive SCA, and when detected it was at significantly lower frequencies and concentrations than in plasma. ECs thus control HIV-1 in the CNS very well. Whether the infrequent and small amounts of HIV-1 RNA in the CSF reflect production from a local reservoir or virion exchange between the blood and the CSF is uncertain.