HIV-1 DNA sequence diversity and evolution during acute subtype C infection

Area of Science:

• Virology
• Genetics
• Immunology

Background:

• The genotypic makeup of HIV-1 DNA during early infection remains poorly understood.
• Understanding early viral evolution is critical for developing effective HIV cure strategies.

Purpose of the Study:

• To longitudinally genotype and quantify subtype C HIV-1 DNA during acute infection.
• To characterize viral DNA sequence profiles in the first year post-infection.

Main Methods:

• Near-full-length, single genome next-generation sequencing was employed.
• Longitudinal sampling and analysis were performed on four women identified during acute HIV-1 infection.

Main Results:

• The majority of viral DNA genomes were intact and lacked APOBEC-3G/F-associated hypermutations.
• Limited genome truncations and minimal evidence of cytotoxic T cell-driven immune selections were observed.
• Viral sequence divergence was primarily driven by single-base substitutions and was limited by early treatment initiation.

Conclusions:

• Early HIV-1 infection is characterized by largely intact viral genomes with limited mutational burden.
• Longitudinal data provide rare insights into the initial stages of HIV-1 infection.
• Findings inform future research directions for HIV cure strategies.