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Smoking Outweighs HIV-Related Risk Factors for Non–AIDS-Defining Cancers
Keri N. Althoff1, Stephen J. Gange1, Chad Achenbach2, Lisa P. Jacobson1, Angel M. Mayor3, Michael J. Silverberg4, Amy Justice5, Richard Moore6, Yuezhou Jing1, Kelly Gebo6
1 Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. 2 Infectious Diseases, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States. 3 Universidad Central del Caribe, Bayamon, PR, United States. 4 Kaiser Permanente Northern California, Oakland, CA, United States. 5 Veterans Affairs Connecticut Healthcare System and Yale Schools of Medicine and Public Health, New Haven, CT, United States. 6 Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Background: The increased burden of non-AIDS-defining cancer (NADC) in HIV-infected adults is likely driven by both HIV-related and other cancer risk factors. The objective of this study is to estimate the population attributable fraction (PAF) for smoking and HIV-related risk factors for NADC, interpreted as the proportion of NADC that could be avoided in HIV-infected adults if all participants had the reference group exposure level.
Methods: Adults (≥18 years) participating in one of 16 contributing cohorts to the North American AIDS Cohort Collaboration on Research and Design who were observed for validated NADC diagnosis from January 1, 2000 to December 31, 2009 were included in this analysis. HIV-related risk factors included CD4 count <200 cells/mm3, HIV RNA ≥200 copies/mL, and clinical AIDS diagnosis. Hepatitis B (HBV) and C (HCV) infections and smoking were also examined. Data on alcohol use, BMI, and HPV infections were not currently available. Risk factors were measured at study entry, with the exception of time-dependent CD4 count and HIV RNA. Cox proportional hazard models with piecewise constant baseline hazard functions were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals ([,]). The PAFs for the modifiable risk factors of interest were estimated using the methodology described by Laaksonen, et al.
Results: Among 39,554 adults who contributed 159,914 person-years, there were 592 incident cancer outcomes distributed as 101 (17%) lung, 96 (16%) anal, 60 (10%) prostate, 54 (9%) Hodgkin, 42 (7%) liver, and 42 (7%) breast cancers. No other cancer type represented more than 5% of the NADC. At baseline, participants who developed NADC were older and had greater proportions with a history of smoking, dyslipidemia, HBV, HCV, and an AIDS diagnosis compared to those without NADC. The PAFs for the variables in the final model can be seen in Figure 1. After excluding lung cancers from the analysis, the PAF for smoking was 39% [23%, 52%].
Conclusions: Programs to prevent smoking initiation among adolescents and young adults at-risk for HIV could prevent up to 46% of NADC in HIV-infected adults. Using ART to preserve immune status, maintain HIV viral suppression, and prevent AIDS-defining illnesses could prevent up to 6% of NADC in HIV-infected adults. In order to reduce the NADC burden in HIV-infected adults, effective interventions to reduce smoking are needed with a continued focus on HIV treatment.