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Genotypic Inference of HIV-1 Tropism Using Population-based Sequencing of V3

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Frequent Detection of HIV-1 Variants With Mixed Coreceptor Usage Among People Who Inject Drugs Infected With

Yosuke Maeda^1,2, Takayuki Chikata^3,4, Takeo Kuwata³

¹Department of Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Open Forum Infectious Diseases

|March 4, 2026

Summary

Mixed human immunodeficiency virus type 1 (HIV-1) infections involving different coreceptor usage were found in 36.1% of people who inject drugs (PWID). This mixed infection may be linked to coreceptor switching and higher viral loads.

Keywords:

CRF01_AE HIV-1 coreceptor mixed infection people who inject drugs

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Prediction of HIV-1 Coreceptor Usage (Tropism) by Sequence Analysis using a Genotypic Approach

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Area of Science:

Virology
Immunology
Infectious Diseases

Background:

Previous research suggested mixed R5 and X4/dual HIV-1 infections might lead to coreceptor switching.
This study aimed to confirm this hypothesis in people who inject drugs (PWID) infected with the CRF01_AE subtype.

Purpose of the Study:

To investigate the prevalence and characteristics of mixed HIV-1 infections with different coreceptor usage in PWID.
To explore the association between mixed infection, coreceptor switch, and plasma viral RNA load (pVL).

Main Methods:

Deep sequencing of viral plasma RNA from PWID.
Amplification and sequencing of the HIV-1 gp120 V3 gene.
Phenotypic assays and sequence-based prediction to determine coreceptor usage of viral variants.

Main Results:

Mixed HIV-1 infections with distinct coreceptor usage were identified in 36.1% of the studied PWID.
R5 variants were typically dominant, with X4/dual variants as minor populations, but one case showed the reverse.
Higher plasma viral RNA load (pVL) was observed in cases of mixed R5 and X4/dual HIV-1 infection compared to R5-only infections.

Conclusions:

Mixed HIV-1 coreceptor usage may be associated with coreceptor switch in CRF01_AE-infected PWID.
Mixed HIV-1 infection appears to correlate with increased plasma viral RNA load (pVL).