Further Limitations of a Model-Based Study of People Living With HIV and Lung Cancer Mortality

To the Editor In an Original Investigation published in a recent issue of JAMA Internal Medicine, Reddy and colleagues¹ used a microsimulation model to calculate cumulative lung cancer mortality in people living with HIV (PLWH) on antiretroviral therapy stratified by age, sex, and smoking exposure.

Reddy and colleagues¹ acknowledged the limitations of a model-based study but did not account for limitations in the studies from which the input parameters were derived. The study¹ used an HIV-associated lung cancer (HALC) mortality risk ratio of 1.7 that was based on the incidence rate ratio of HALC reported in a Veterans Aging Cohort Study by Sigel et al.² However, the cohort had an understandably large sex disparity with 98% of the cohort being male,² and this sex disparity is problematic. A study by Engels et al³ reported that among PLWH, the standardized rate ratio of lung cancer was 2-fold greater in women compared with men. Hence the HALC mortality risk ratio used by Reddy et al¹ may underestimate mortality in the female PLWH population. The sensitivity analyses that were carried out used a range of parameter estimates including alternative HALC risk ratios from 1.0 to 1.9. This range of parameter estimates could therefore be insufficient as the actual HALC rate ratio in female patients could potentially be up to 2-fold greater than 1.7.