High concordance of human immunodeficiency virus-1 genotypic drug resistance generated from paired cerebrospinal fluid and plasma in antiretroviral therapy -naive or -experienced patients

TL;DR

This study shows that HIV drug resistance in cerebrospinal fluid matches that in blood, suggesting resistance in the brain comes from the bloodstream.

Contribution

Demonstrates high concordance of HIV-1 drug resistance mutations between cerebrospinal fluid and plasma in ART-naive and -experienced patients.

Findings

CRF01_AE was the most common HIV-1 genotype in the study population.

NNRTI-related resistance mutations, especially V179D/E, were most prevalent and mainly found in ART-naive patients.

CSF drug resistance mutations were nearly identical to those in plasma, with no unique mutations identified in CSF.

Abstract

The development of human immunodeficiency virus (HIV) drug resistance significantly impairs patients’ quality of life. However, the HIV-1 drug resistance patterns in the central nervous system (CNS) have been poorly studied.

We aimed to compare HIV-1 genotypes and drug resistance mutations (DRMs) derived from the cerebrospinal fluid (CSF) and plasma of antiretroviral therapy (ART)-naive or -experienced patients.

The matched CSF and plasma samples from 59 patients with HIV were subjected to HIV proteinase (PR), reverse transcriptase (RT), and integrase (IN) gene sequencing. To determine the HIV-1 genotypes, sequences were assessed with the Context-based Modelling for Expeditious Typing (COMET) tool, and the neighbour-joining (NJ) phylogenetic tree was used to confirm the results. Quality control based on genotype and phylogenetic tree analysis was conducted to assess potential sequence contamination during the detection process. The HIV-1 drug resistance database of Stanford University was used to identify DRMs and sensitivity to four drug classes [protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and integrase strand transfer inhibitors (INSTIs)].

Of the 59 patients with HIV with matched CSF and plasma samples, samples from 37 were included in the study after excluding the samples that failed to be successfully amplified. CRF01_AE was the most frequently occurring genotype, with a frequency of 46.0% (17/37), followed by CRF07_BC (27.0%, 10/37) and CRF55_01B (10.8%, 4/37). Among the 37 patients, 37.8% (14/37) carried at least one DRM, and the mutation sites were consistent in both CSF and matched plasma, except one. NNRTI-related resistance mutations were the predominant DRMs, particularly V179D/E, present in 71.4% (10/14) of patients with DRM sites, primarily in ART-naive patients.

A high concordance of HIV-1 DRMs between CSF and plasma samples was observed. No unique mutations were identified in CSF other than those in plasma, indicating that the mutant variants in CSF were derived from blood.

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