Association of HIV Envelope Susceptibility Signatures to Broadly Neutralizing Antibodies and Presence of p24 CTL Epitopes During Acute HIV-1 Infection.

BACKGROUND

Broadly neutralizing antibodies (bNAbs) targeting HIV-1 envelope (Env) are being studied for long-acting HIV treatment and post-treatment remission in combination with therapeutic vaccines containing conserved cytotoxic T-lymphocyte (CTL) epitopes. Understanding the prevalence of bNAb susceptibility and CTL epitopes in people with acute and early HIV-1 infection could inform our understanding of early host virus interactions and epitope conservation in this population.

SETTING

The Italian Network of Acute HIV Infection (InAction) cohort.

METHODS

Pre-antiretroviral therapy (ART) plasma of 110 people with HIV who initiated ART during acute and early HIV-1 infection was genotyped for Env and the capsid (p24) region of Gag, using short-read sequencing. Single-genome sequencing of full-length viral genomes was performed for 4 participants. Susceptibility to teropavimab (TAB) and zinlirvimab (ZAB) was predicted using amino acid signatures, while p24 sequences were analyzed for the presence of CTL epitopes.

RESULTS

Env and p24 sequences were obtained for 80 and 75 participants, with 45 having both. A total of 44 full-length sequences from 4 participants with full-length single-genome sequencing were recovered. The shortest susceptibility signatures were observed in 51 of 80 participants for ZAB and in 59 of 80 participants for TAB, while the longest bNAb susceptibility signatures were present in 14 of 80 participants for TAB and ZAB. Two p24 CTL epitopes linked to viral control were present in 95% and 87% of all participants. Prevalence of bNAb susceptibility signatures occurred independently of p24 CTL epitopes.

CONCLUSIONS

The findings contribute to our understanding of bNAb susceptibility and epitope prevalence during early stages of HIV-1 infection, informing future treatment and cure strategies.