Cancer incidence and risk factors among people with HIV in REPRIEVE.

OBJECTIVE: Cancer is a leading cause of morbidity and mortality among people with HIV (PWH), who face a greater risk than the general population. An enhanced understanding of cancer incidence and associated risk factors among PWH receiving effective antiretroviral therapy (ART) may guide targeted preventive interventions. DESIGN AND METHODS: Analyses included REPRIEVE participants without cancer at baseline, followed until first cancer incidence or trial end. Incidence rates were computed for all cancers, AIDS-defining cancers (ADCs), non-AIDS-defining cancers (NADCs), both infection-related and noninfection-related, by Global Burden of Disease (GBD) region and sex. Cause-specific Cox models assessed associations with traditional [age, sex, region, body mass index (BMI), smoking] and HIV-related (nadir CD4, baseline CD4, CD4/CD8 ratio) factors. RESULTS: Among 7507 participants (31.5% women) with median follow-up of 5.6 (Q1-Q3: 4.6-6.3) years, 219 incident cancers occurred [incidence rate (IR): 5.6 per 1000 person-years, 95% confidence interval (CI): 4.9-6.4]. Noninfection-related NADCs were most common (3.4 [2.8-4.0]), followed by infection-related NADCs (1.5 [1.1-1.9]) and ADCs (0.6 [0.4-0.9]). Incidence was higher in males and participants from high-income countries. Leading cancers included prostate, breast, lung, and anal. Older age, high-income country residence, and current smoking were independently associated with higher cancer risk, whereas sex, BMI, and HIV-related factors were not. CONCLUSIONS: In a global cohort of PWH on effective ART, cancer remains an important comorbidity, with risk varying by demographic and behavioral factors. Targeted prevention strategies, particularly smoking cessation and age- and region-specific cancer screening approaches, may help reduce cancer burden in this population.