Among people living with HIV who are initiating antiretroviral therapy (ART), those with obesity potentially face a higher long-term risk of cardiovascular disease (CVD), cancer, or death, according to an observational study.
Over a maximum of 15 years following ART initiation (median 7 years), the primary composite outcome of CVD, cancer, or death occurred in 19.1 percent of participants with obesity vs 12.4 percent of those without obesity (p=0.0029), reported Prof Cristina Mussini from the University of Modena and Reggio Emilia, Modena, Italy. [EClinicalMedicine 2026;doi:10.1016/j.eclinm.2026.104150]
Obesity was associated with a 47-percent increased risk of the primary composite outcome in the unadjusted Cox model (hazard ratio [HR], 1.47, 95 percent confidence interval [CI], 1.14–1.90; p=0.003). When adjusted for baseline confounders, the model consistently showed a clinically relevant risk increase (adjusted HR [aHR], 1.28, 95 percent CI, 0.98–1.67; p=0.073), as Mussini and colleagues noted.
“Results were similar, although the magnitude of the association was attenuated, when we analysed the endpoint considering only comorbidities (aHR, 1.08, 95 percent CI, 0.75–1.55; p=0.67) and after restricting cancers to BMI-related cancers (aHR, 1.17, 95 percent CI, 0.86–1.60; p=0.31),” they added.
Stratified analysis showed no evidence for interaction with age (p=0.758), although there was a trend for a larger effect among younger participants with obesity (18–30 years: aHR 1.83; 31–60 years: aHR 1.49; >60 years: aHR 1.20).
“In light of our findings suggesting an association between obesity at ART initiation and poorer clinical outcomes in people living with HIV, clinicians should be encouraged to address obesity,” Mussini and colleagues said.
It is important to reduce excess weight at ART initiation, given that several studies have reported weight gain during ART treatment, following the adoption of integrase inhibitors as the preferred ART regimen, according to the authors. [Lancet HIV 2025;12:e473-e484]
If the findings are confirmed in other studies, clinicians should recognize young and middle-aged individuals with obesity as a vulnerable subgroup prone to developing serious clinical outcomes, they added.
The study included 11,652 people living with HIV (median age 38 years, 20.7 percent female) who are initiating ART. Of these, 5.6 percent individuals had obesity (BMI ≥30 kg/m2). People with obesity were more likely to be older (median age, 41 vs 38 years; p<0.001) and were less likely to be men having sex with men (31.7 percent vs 44.8 percent; p<0.001) compared with those who had no obesity. At ART initiation, people with obesity also had higher baseline CD4 count (389 vs 349 cells/mm3; p<0.001) and higher prevalence of diabetes (6.8 percent vs 1.5 percent; p<0.001).
During the follow-up, a total of 837 adverse clinical events occurred, including 122 CVD, 374 cancers, and 341 deaths.