HIV Coreceptor Tropism in Paired Plasma, Peripheral Blood Mononuclear Cell, and Cerebrospinal Fluid Isolates from Antiretroviral-Naïve Subjects

Abstract

A survey of HIV coreceptor usage in cerebrospinal fluid (CSF) samples, peripheral blood mononuclear cells (PBMCs), and plasma samples from naïve seropositive patients was conducted. One hundred patients were enrolled in this study. Of the 100 patients, 36 had a primary or recent infection (P-RI), 31 had an early chronic infection (>350 CD4 cells) (ECI), and 33 had a late chronic infection (LCI). All 3 compartments were sampled in a subset of 33 participants, while the remaining 67 patients provided plasma samples and PBMCs only. Seventy-seven patients harbored the R5 virus in plasma samples and had a significantly higher median and percentage of CD4 ؉ T cells than patients with X4 virus (437 and 281 cells/l, respectively; P ‫؍‬ 0.0086; 20.6% and 18.6%, respectively). The X4 strain was detected more frequently in patients with LCI than in patients with P-RI or ECI (39.3%, 19.4%, and 9.6%, respectively; P ‫؍‬ 0.0063). PBMC and plasma tropism was concordant in 90 patients, and 73 had the R5 strain. Among patients with discordant results, 4 had the R5 virus in their plasma and the X4 virus in PBMCs; 6 showed the opposite profile. Plasma, PBMC, and CSF tropism determinations were concordant in 26/33 patients (21 patients had R5, and 5 had X4). The tropism was discordant in 5/33 patients, with the X4 virus in plasma and R5 in CSF; the HIV tropism in PBMCs was X4 in 3 patients. The remaining 2/33 patients had the R5 virus in plasma and PBMCs and the X4 virus in CSF; one of these patients had a P-RI. The discordant tropism in CSF and blood may have implications for chemokine (C-C motif) receptor 5 (CCR5) antagonist use in patients with limited response to antiretroviral therapy (ART) or in responding patients evaluated for simplification of treatment.

Genotypic Prediction of Human Immunodeficiency Virus Type 1 Tropism by Use of Plasma and Peripheral Blood Mononuclear Cells in the Routine Clinical Laboratory

“…(16). Our observations are in agreement with three studies on 38, 34, and 100 patients, which also showed high concordances (82% to 90%) between plasma and PBMC samples (18,23,24). The observed high concordances between HIV RNA and HIV DNA assessments may indicate that HIV DNA-derived tropisms also by and large reflect the major HIV tropism within a patient.…”

Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy

“…As systemic infection progresses, CSF viruses may show more diverse compartmentalization involving R5 viruses that infect macrophages and related cells (referred to as M-tropic) [24][25][26][27][28][29]. While full formal proof of this remains to be shown, it is likely that these viruses are important in the development of encephalitis, in which productive infection can be identified in perivascular and parenchymal macrophages and microglial cells [30].…”

Genotypic Tropism Testing in HIV-1 Proviral DNA Can Provide Useful Information at Low-Level Viremia

“…For plasma RNA samples, G2P was set at a false-positive rate (FPR) of 10%, according to guidelines on the clinical management of HIV-1 tropism testing (8). For pvDNA samples, G2P was set at FPR values of both 10%, as reported in several studies (2,11,18,26,27), and 20%, as recommended by guidelines (8). Thus, sequences with FPRs of Ͻ10% from both plasma RNA and pvDNA samples and Ͻ20% from pvDNA samples were considered X4/dualmixed tropic.…”