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Cancer Risks and Factors · Journal article
Eclinicalmedicine · August 15, 2026
Encouraging direction, but not yet definitive.
This prospective cohort study of 11,652 HIV-positive individuals initiating antiretroviral therapy found that obesity (BMI ≥30 kg/m²) was associated with an elevated unadjusted 15-year cumulative risk of CVD, cancer, or death (19.1% vs 12.4%, p=0.0029). However, after adjustment for confounders, the association was attenuated to borderline non-significance (aHR 1.28, 95% CI 0.98–1.67, p=0.073), with a possible age-related gradient suggesting stronger effects in those under 60 years.
Prospective cohort study. ART-naïve adults with HIV enrolled in the Icona Foundation study across 96 sites in Italy; aged 18+ years with BMI >18.5 kg/m²; free from AIDS, CVD, and cancer at ART initiation; median age 38 years (IQR 31–46), 20.7% female. Intervention: Obesity at ART initiation (BMI ≥30 kg/m²). Compared with: No obesity at ART initiation (BMI 18.5–29.9 kg/m²). n = 11,652. 96 sites in Italy.
Unadjusted 15-year cumulative risk of CVD/cancer/death: 19.1% (95% CI 14.1–24.9%) with obesity vs 12.4% (95% CI 11.3–13.4%) without obesity, log-rank p=0.0029 Adjusted hazard ratio for obesity: aHR 1.28 (95% CI 0.98–1.67), p=0.073 Total 837 events recorded: 122 CVD, 374 cancers, 341 deaths among 11,652 participants
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Clinicians should be aware that obesity at ART initiation is associated with a clinically meaningful absolute increase in 15-year risk of major adverse events (6.7 percentage point increase), but the adjusted association is borderline statistically significant and may be partly confounded. Further investigation is warranted, particularly in younger and middle-aged PWH where the signal is stronger.
Prospective cohort study with adequate sample size and hard clinical outcomes (CVD, cancer, death), but unadjusted effect is attenuated to borderline significance after adjustment (aHR 1.28, 95% CI 0.98–1.67, p=0.073), limiting definitive causal inference.
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Quoted from the source exactly as published.
Clinicians should be aware that obesity at ART initiation is associated with a clinically meaningful absolute increase in 15-year risk of major adverse events (6.7 percentage point increase), but the adjusted association is borderline statistically significant and may be partly confounded. Further investigation is warranted, particularly in younger and middle-aged PWH where the signal is stronger.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background Altered adipose tissue biology plays a key role in the development of cardiovascular disease (CVD) and cancer and contributes to mortality. We assessed the association between obesity in people with HIV (PWH) at antiretroviral therapy (ART) initiation and the risk of clinical events. Methods In this prospective cohort study, we included ART-naïve adults PWH enrolled in the Italian Cohort Naive Antiretrovirals (Icona) Foundation study cohort in Italy across 96 sites between January 1997 and July 2025. Participants were included if they initiated ART, had body mass index (BMI) > 18.5 kg/m 2, and were free from AIDS, CVD, and cancer at ART initiation. Participants were classified as having obesity, defined as BMI ≥ 30 kg/m 2, or not having obesity, defined as BMI 18.5–29.9 kg/m 2, at ART initiation. The primary outcome was the first occurrence of CVD, cancer, or death. We performed a standard survival analysis with time-fixed covariates at baseline with a composite outcome of CVD/cancer/death. We hypothesized that age may be an effect measure modifier: results are presented after stratification by age (young [18–30], middle aged [31–60] and older [>60 years]). Findings A total of 11,652 PWH (20.7% females, median age 38 years [Inter Quartile Range (IQR): 31, 46]) were included: 11,005 (94.4%) were people without obesity and 647 (5.6%) people with obesity. A total of 837 events were recorded: 122 CVD, 374 cancers and 341 deaths. By 15 years from ART initiation, the risk of CVD/cancer/death was 19.1% in people with obesity (95% Confidence Interval [CI]: 14.1–24.9%) vs. 12.4% in people without obesity (95% CI:11.3–13.4%, log-rank p=0.0029). After controlling for confounding, the difference was attenuated (adjusted hazard ratio [aHR] 1.28 [95% CI:0.98–1.67], p=0.073). Although we did not find evidence for interaction (p-value = 0.758) there was a trend for a larger effect among younger PWH: young (aHR 1.83 [95% CI 0.74, 4.56]), middle aged (aHR 1.49 [95% CI 1.11, 2.00]) and older (aHR 1.20 [95% CI 0.60, 2.41]). Interpretation Obesity at ART initiation may be associated with a clinically meaningful increase in the risk of CVD, cancer, and death. We found weak evidence of a possible age-related gradient, with larger effect size in PWH under 60 years of age, which warrants further investigation. Funding The Italian Cohort Naive Antiretrovirals (Icona) Foundation Study is supported by unrestricted grants from Gilead Sciences, ViiV Healthcare, Merck Sharpe & Dohme.
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