HCV adaptation to HIV coinfection

Area of Science:

• Virology
• Genetics
• Infectious Diseases

Background:

• Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection is a significant health concern.
• HIV infection may influence the intra-host evolution of HCV, leading to genetic divergence in viral populations.
• Understanding these genetic differences is crucial for managing co-infected patients.

Purpose of the Study:

• To investigate genetic differences in HCV hypervariable region 1 (HVR1) variants between HIV-HCV co-infected patients (CIP) and HCV mono-infected patients (MIP).
• To explore the potential of these genetic differences for detecting HIV infection in HCV-infected individuals.

Main Methods:

• Analysis of nucleotide sequences from 28,622 intra-host HCV HVR1 variants from 112 CIP and 176 MIP.
• Representation of sequences using 148 physical-chemical (PhyChem) indexes of DNA nucleotide dimers.
• Application of linear projection analysis, probabilistic neural networks (PNN), and naïve Bayesian (NB) classifiers.

Main Results:

• Significant differences (p < .0001) in 7 PhyChem properties were observed between HVR1 variants from CIP and MIP.
• Distinct distributions of HVR1 variants in a 2D-space were identified using 29 PhyChem features, with only ~1.3% overlap.
• PNN and NB classifiers achieved high accuracy (AUROC ≥ 0.96) in distinguishing between CIP and MIP HVR1 variants.

Conclusions:

• Marked genetic differences in HCV HVR1 variants suggest altered intra-host HCV evolution in the presence of HIV.
• Identified PhyChem features may serve as biomarkers for detecting HIV infection in HCV co-infected patients.
• This approach could facilitate monitoring for HIV introduction in high-risk populations with high HCV prevalence.