Effect of Body Weight and Other Metabolic Factors on Risk of Non-Small Cell Lung Cancer among Veterans with HIV and a History of Smoking

SIMPLE SUMMARY: Among people living with HIV (PWH), there has been an increasing incidence of non-small cell lung cancer (NSCLC) and metabolic abnormalities, such as diabetes and high cholesterol, which affect the risk of NSCLC. In this article, we evaluate which metabolic risk factors increase the risk of NSCLC among PWH who smoke. Through a retrospective study that includes 33,351 veterans, we found that the risk of NSCLC was lower in well-controlled PWH (1.46 vs. 2.06/1000 patient/year [PY]). Metabolic factors associated with higher NSCLC risk included lower body weight at HIV diagnosis and a remote history of involuntary weight loss in PWH regardless of whether they had a well-controlled infection or not. Lower HDL and triglyceride levels increased the risk of NSCLC only in non-well-controlled smokers. Our results suggest these factors may be important to consider in targeting surveillance and for early identification of NSCLC in PWH smokers. ABSTRACT: Among people living with HIV (PWH), there has been an increasing incidence of non-small cell lung cancer (NSCLC) and metabolic abnormalities, including dyslipidemia, which can modulate NSCLC risk. In this article, we evaluate which metabolic risk factors are associated with incident risk among PWH who smoke. This is done through a retrospective cohort study, using data of HIV+ veterans who smoke from the nationwide Veterans Affairs (VA) healthcare system. Data on diagnostic codes, medication, and laboratory values of 33,351 veterans were obtained using the VA’s Corporate Data Warehouse and Central Cancer Registry. We calculated NSCLC incidence and utilized Cox regression to determine metabolic factors associated with NSCLC risk. HIV+ cohort was 97.4% male; median age = 47 years and 20,050 (60.1%) well-controlled (≥80% follow-up time undetectable viral load). Crude incidence rates were lower in well-controlled PWH (1.46 vs. 2.06/1000 PY). Metabolic factors associated with incident NSCLC risk included lower BMI at HIV diagnosis and cachexia history in both groups, while HDL and triglycerides were significant in non-well-controlled smokers only. Our findings that lower BMI at HIV diagnosis, history of cachexia among individuals with well-controlled HIV, and cachexia presence at diagnosis are associated with increased risk of developing NSCLC in PWH with a history of smoking have important implications.