>10% weight gain during first two years of ART linked to double the risk of cardiometabolic disease

A major article in Clinical Infectious Diseases reports associations between weight gain and metabolic consequences during the first two years on first-line ART. [1]

Combined data from two US cohort studies collected between 2000 and 2013 show that people who gained >10% weight were two-fold more likely to develop cardiometabolic disease.

As background, weight gain as part of the return-to-health phenomenon is a positive indicator for people who at baseline are underweight or have normal BMI. The opposite is true of those who are overweight or obese.

Two observational ACTG cohorts were used to recruit 2624 participants. Demographics included: female (19%), Black (35%), Hispanic (22%) and mean age was 38 years (SD +/– 10). BMI at baseline was classified as normal for 47%, whilst 33% were overweight and 17% were obese.

Mean weight change in year one was +3.6 kg (SD: 7.3 kg) and was greater in women than men (4.2 kg vs 3.5 kg). This trend continued at 10 years with a mean weight change of +7.1 kg (SD: 10.7 kg).

Over the first year, 22% of participants gained >10% of their baseline weight in the first year, and after ten years this increased to 40%. The paper noted that the 10-year increase was similar to the general US population (36%).

In adjusted analyses, baseline CD4 count below 200 cells/mm³ was associated with weight gain (HR: 5.02; 95% CI: 4.23 to 5.95) and emergent obesity (HR: 2.76; 95% CI: 2.25 to 3.39). Metabolic markers shifted per kilogram of weight gain, with small increases of fasting glucose, total cholesterol and LDL, whilst HDL decreased.

Weight gain of >10% was associated with doubling the rate of incident diabetes (HR 2.01; 95% CI: 1.30 to 3.08, n=130) and metabolic syndrome (HR 2.02; 95% CI: 1.55 to 2.62, n=360) and increasing cardiometabolic events 1.5-fold (HR 1.54; 95% CI: 1.22 to 1.95, n=424).

However, cardiovascular events were not associated with weight gain (HR 0.62, 95% CI 0.22 to 1.67, n=28).

Weight loss of >5% was associated with a reduced risk of metabolic syndrome (HR 0.60, 95% CI 0.37 to 0.98).

comment

The results were not stratified by ART use and the study design did not include matching. Data also predates both TAF and second-generation integrase inhibitors that are currently linked to weight gain.

The authors do not report an increase in cardiovascular events which is probably due to the young mean age of the cohort (38 ± 10 years). The increased signal for cardiometabolic complications suggests that CVD incidence might easily increase in the future.

An overview of weight gain and ART use by Prof Andrew Carr was included in the 2023 BHIVA conference and reported in HTB. [2]