Marijuana Use Impacts Midlife Cardiovascular Events in HIV-Infected Men

Abstract

Background: Marijuana use is prevalent among persons infected with human immunodeficiency virus (HIV), but its long-term effects on HIV disease progression and comorbidities are unknown.

Methods: In this prospective study of 558 HIV-infected men enrolled in the Multicenter AIDS Cohort Study between 1990 and 2010, there were 182 HIV seroconverters and 376 with viral suppression on combination antiretroviral therapy (ART). Associations between heavy marijuana use and HIV disease markers or white blood cell (WBC) count were examined using mixed-effects and linear regression models. Effects of marijuana use on cardiovascular (CV) events and other endpoints were estimated using Kaplan-Meier and logistic regression analyses.

Results: The median baseline age of participants was 41, 66% were white, 79% had education >12 years, and 20% reported heavy marijuana use at ≥50% of biannual visits during follow-up. Long-term heavy marijuana use showed no significant associations with viral load, CD4 counts, AIDS, cancer, or mortality in both cohorts but was independently associated with increased CV events between ages 40-60 after adjusting for age, tobacco smoking, viral load, and traditional risk factors (odds ratio [OR], 2.5; 95% confidence interval [CI] 1.3, 5.1). Marijuana and tobacco use were each independently associated with higher WBC counts in adjusted models (P < .01); the highest quartile of WBC counts (≥6500 cells/µL) was associated with increased CV events (OR 4.3; 95% CI, 1.5, 12.9).

Conclusions: Heavy marijuana use is a risk factor for CV disease in HIV-infected men ages 40-60, independent of tobacco smoking and traditional risk factors.

Keywords: AIDS; HIV; cardiovascular disease; marijuana.

Figure 1.

Cohort selection and longitudinal patterns of marijuana and smoking exposures. A, Cohort selection flowchart. B, Lasagna plots illustrating self-reported patterns of marijuana use (top panel) and cigarette smoking (bottom panel) among participants in the chronic HIV cohort. Each row depicts visit-level exposure data for an individual in the study interval used for group classification. Abbreviations: cART, combination antiretroviral therapy; HCV, hepatitis C virus; HIV, human immunodeficiency virus.

Figure 2.

Association between marijuana use, HIV disease marker trajectories, and health outcomes. A, Mean values of HIV disease markers by marijuana use. B, Kaplan-Meier curves of AIDS diagnoses, mortality, cancer diagnoses, and cardiovascular events for the merged HIV+ cohort stratified by marijuana use. P values denote pair-wise log-rank test vs control group. Abbreviations: HIV, human immunodeficiency virus.

Figure 3.

Heavy marijuana use and white blood cell (WBC) count are independently associated with increased odds of cardiovascular (CV) events. A, Estimated mean trajectories for WBC (top panels) and neutrophil counts (bottom panels) by cigarette smoking (left panel) or by marijuana use and cigarette smoking (right panel), for the merged HIV+ cohort with follow-up between ages 40 and 60 years from mixed effects models adjusted for viral load, race, age at entry, education, and total cholesterol (Supplementary Table 3). B, Kaplan-Meier curves of first CV event stratified by smoking only (left panel) or by marijuana use and cigarette smoking (right panel) for the merged HIV+ cohort with follow-up between ages 40 and 60. Mj+ denotes heavy marijuana users, Mj−, occasional or nonusers, Sm+, moderate or heavy smokers (≥0.25 packs/day, average), Sm−, light or nonsmokers, P values, pair-wise log-rank test vs control group. C, Forest plot showing estimated odds of adverse CV events for the indicated covariates from logistic regression model 2 (Table 3) with WBC values by quartiles. Abbreviations: CI, confidence interval; HIV, human immunodeficiency virus; Mj, marijuana; Sm, smoking; WBC, white blood cells.