Journal Article

Differential HIV-1 Proviral Defects in Children vs. Adults on Antiretroviral Therapy

Capoferri, Adam A., Katusiime, Mary Grace, Bale, Michael J., Kearney, Mary F., Luke, Brian T., Shao, Wei, Hasson, Jenna M., van Zyl, Gert, Patro, Sean C., Cotton, Mark F.

2025

Overview

HIV-1 proviral landscapes were investigated using near-full-length HIV single-genome sequencing on blood samples from five children with vertically acquired infection and on ART for ~7–9 years. Proviral structures were compared to published datasets in children prior to ART, children on short-term ART, and adults on ART. We found a strong selection for large internal proviral deletions in children, especially deletions of the env gene. Only 2.5% of the proviruses were sequence-intact, lower than in the comparative datasets from adults. Of the proviruses that retained the env gene, >80% contained two or more defects, most commonly stop codons and/or gag start mutations. Significantly fewer defects in the major splice donor site (MSD) and packaging signal were found in the children on short or long-term ART compared to the adults, and tat was more frequently defective in children. These results suggest that different selection pressures may shape the proviral landscape in children compared to adults and reveal potentially different genetic regions to target for measuring the intact HIV reservoir and for achieving HIV remission in children.

• Publisher: MDPI AG,MDPI
• Subject: Adult / Analysis / Anti-Retroviral Agents - therapeutic use / Antiretroviral drugs / Antiretroviral therapy / Antiviral agents / Child / Child, Preschool / Children / Cloning / Codons / Datasets / Dosage and administration / Drug therapy / Drugs / Env gene / env Gene Products, Human Immunodeficiency Virus - genetics / Female / Gag protein / Genome, Viral / Genomes / Health aspects / HIV / HIV in children / HIV infection / HIV Infections - drug therapy / HIV Infections - virology / HIV latency / HIV persistence / HIV proviruses / HIV reservoir / HIV-1 - drug effects / HIV-1 - genetics / Human immunodeficiency virus / Humans / intact provirus / Male / Maternal-fetal exchange / Mutation / Patient compliance / Prevention / Proviruses / Proviruses - drug effects / Proviruses - genetics / Remission / Risk factors / Tat protein