Obesity-Related Single-Nucleotide Polymorphisms and Weight Gain Following First-Line Antiretroviral Therapy

Area of Science:

• Genetics and Genomics
• Infectious Diseases
• Metabolic Health

Background:

• Investigating the association between obesity-related single-nucleotide polymorphisms (OR-SNPs) and weight gain in people with human immunodeficiency virus (PWH) initiating antiretroviral therapy (ART).
• Understanding the genetic predispositions that may influence weight changes during HIV treatment is crucial for managing metabolic health in PWH.

Approach:

• Genotyped 1021 ART-naive PWH from the Spanish HIV Research Cohort for 14 OR-SNPs.
• Analyzed weight and body mass index (BMI) changes at 96 weeks post-ART initiation using adjusted linear mixed models.
• Examined associations between specific genotypes (ZC3H4 rs3810291 and BCDIN3D/FAIM2 rs7138803) and weight gain.

Key Points:

• Mean weight gain was 2.90 kg over 96 weeks.
• Factors like female sex, origin, prior AIDS, lower CD4+ count, high viral load, and specific ART (tenofovir alafenamide) were associated with greater weight gain.
• Significant associations found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotype with increased weight and BMI.

Conclusions:

• Genetic factors, particularly specific OR-SNPs, may contribute to weight gain following ART initiation in PWH.
• Further studies are required to validate these genetic associations and elucidate the underlying mechanisms.
• Identifying individuals at higher genetic risk for weight gain could inform personalized management strategies during HIV treatment.