Weight Gain After Antiretroviral Therapy Initiation May Have a Genetic Component

Genetics may play a role in weight gain after ART initiation in HIV-positive individuals, suggesting obesity-related SNPs may help with appropriate ART regimen selection.

For individuals with HIV infection, weight gain after antiretroviral therapy (ART) initiation may have a genetic component, according to results of a study published in Clinical Infectious Diseases.

In this retrospective observational study, researchers analyzed data captured from HIV-positive patients (N=16,759) who initiated ART in 2014. Patients who had weight and height information 24 weeks prior to ART initiation (n=1021) were evaluated for changes in weight at 96 weeks following initiation. The risk for ART-associated weight gain was investigated in relation to 14 obesity-related single nucleotide polymorphisms (SNPs).

Among patients included in the analysis, the median age was 35.76 (IQR, 29.59-43.23) years, 88.15% were men, 61.31% had a normal BMI (range, 18-24.9 kg/m2) at baseline, 71.30% acquired HIV through homosexual contact, the median CD4+ count was 426 (IQR, 274-591) cells/µL, the median HIV viral load was 45,986 (IQR, 14,900-160,216) copies/mL, and 62.98% initiated ART regimens comprising 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus 1 integrase strand transfer inhibitor (INSTI).

At 96 weeks following ART initiation, the overall mean weight gain among the study population was 2.90 kg (P <.001), with a mean increase in BMI of 0.98 kg/m2 (P <.001).

The researchers used multivariable logistic regression to determine factors independently associated with weight gain after ART initiation. Significant factors were as follows:

  • Prior diagnosis of an AIDS-defining condition (mean difference [MD], 4.164 kg; P <.001);
  • Sub-Saharan Africa ancestry (MD, 2.684 kg; P =.011);
  • Female vs male sex (MD, 1.339 kg; P =.041);
  • High vs low HIV viral load (>100,000 vs <10,000 copies/mL; MD, 1.346 kg; P =.011);
  • Use of tenofovir alafenamide (TAF)- and emtricitabine (FTC)-based ART (MD, 1.076; P =.046);
  • Obesity at baseline (MD, -1.692 kg; P =.017); and
  • Hepatitis C virus antibodies at baseline (MD, -2.060 kg; P =.023)

Compared with CD4+ counts of less 200 cells/µL, CD4+ counts of 500 or more (MD, -3.514 kg; P <.001), 350 to 499 (MD, -3.640 kg; P <.001), and 200 to 349 (MD, -3.593 kg; P <.001) cells/µL were significantly associated with weight gain after ART initiation.

[I]ndividual obesity-related SNPs could help to develop risk scores for predicting overweight and obesity and their related diseases and using them to make clinical decisions when selecting antiretroviral regimens.

In the genetic analysis, SNPs in the genes zinc finger CCCH-type containing 4 (ZC3H4) and BCDIN3 domain-containing RNA methyltransferase (BCDIN3D)/FAS apoptotic inhibitory molecule 2 (FAIM2) showed significant interaction with post-ART initiation weight change.

For the SNP in ZC3H4, carriers of the GG genotype had a mean weight gain of 4.26 kg compared with 2.66 kg for carriers of AA or AG genotypes (P =.007). For the SNP in BCDIN3D/FAIM2, GG genotype carriers had a mean weight gain of 3.35 kg compared with 2.51 kg for carriers of genotypes AA or AG (P =.010). Similar trends were observed for mean change in BMI in comparisons between SNP genotypes. Increases in weight of more than 10% by week 96 were significantly more likely among patients with the ZC3H4 GGgenotype compared with those with AA or AG genotypes (P =.029).

Study limitations include the linkage disequilibrium observed between candidate SNPs.

According to the researchers, “individual obesity-related SNPs could help to develop risk scores for predicting overweight and obesity and their related diseases and using them to make clinical decisions when selecting antiretroviral regimens.”

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.

References:

Berenguer J, Jarrín I, Bellón JM, et al. Obesity-related SNPs and weight gain followingfirst-line antiretroviral therapy. Clin Infect Dis. Published online November 8, 2022. doi:10.1093/cid/ciac880