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.
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.
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