Mitochondrial Haplogroups and Weight Gain After Initiating ART in Patients With HIV

Area of Science:

• Genetics
• Immunology
• Metabolism

Background:

• Antiretroviral therapy (ART) initiation in treatment-naive persons with HIV (PWH) can lead to significant weight gain.
• The underlying mechanisms driving ART-associated weight gain are not fully understood.
• Mitochondrial DNA (mtDNA) plays a crucial role in cellular energy metabolism.

Purpose of the Study:

• To investigate the association between mitochondrial DNA (mtDNA) haplogroups and weight and body mass index (BMI) changes in treatment-naive PWH initiating first-line ART.
• To explore the potential role of mitochondrial genetics in ART-induced weight gain.

Main Methods:

• A cohort of 1019 treatment-naive PWH initiating first-line ART since 2014 was studied.
• Weight and BMI were measured at baseline and at 96 weeks post-ART initiation.
• Statistical analyses were performed to assess the association between major UK mtDNA haplogroups and changes in weight and BMI.

Main Results:

• The mean increase in weight and BMI over 96 weeks was 2.90 kg and 0.98 kg/m2, respectively.
• A significant adjusted association was found between the major UK mtDNA haplogroup and lower weight and BMI increase.
• This suggests a potential protective effect of certain mtDNA haplogroups against excessive weight gain.

Conclusions:

• Mitochondrial genetics, specifically mtDNA haplogroups, may play a role in modulating weight gain following ART initiation in PWH.
• These findings highlight the complex interplay between host genetics and ART response.
• Further research is warranted to elucidate the precise mechanisms and clinical implications.