We found a main effect of group on net IGT scores, such that MJ+ had overall lower net IGT scores than HC. These findings may highlight differences in decision-making performance between young adult MJ+ and HC. Results from this study underscore the importance of interventions targeted at reducing risky decision-making in young adult MJ users. As our study is cross-sectional, further longitudinal research is needed to understand whether impairments in MJ users are related to the neurotoxic effects of MJ or if riskier decision-making may be present in MJ users prior to initiation of use, and whether these differences persist after abstinence.Lung disease remains a common comorbidity in persons living with HIV, despite the widespread use of combination antiretroviral therapy that has substantially reduced morbidity and mortality related to opportunistic lung infections. Previous studies in the U.S. have reported higher incidence of both infectious and non-infectious lung diseases in HIV-infected compared to uninfected populations. This increased prevalence is explained, in part, by more tobacco smoking among HIV+ individuals, while HIV disease-related factors including unsuppressed viral load and low CD4 T cell count may also contribute to higher rates of lung disease. The high prevalence of non-infectious obstructive lung disease is expected to continue to increase among HIV+ individuals in the U.S. and globally, yet the potential contributions of other risk factors remain poorly defined.
Smoked cannabis grow system is a potential risk factor for lung disease, as it contains many of the same toxic constituents present in tobacco smoke. In the U.S., the proportion of HIV+ individuals who frequently smoke marijuana is higher than in the general population and has increased in recent years. Previous studies of HIV-uninfected emphysema,while other studies reported no significant association between marijuana smoking and these diagnoses or other measures of lung health. Among HIV-infected individuals, few data exist regarding the association between marijuana smoking and respiratory burden, despite high prevalence of lung disease in HIV-infected populations and its associated mortality and morbidity. The aims of this study were to investigate the effects of marijuana smoking on infectious and non-infectious pulmonary diagnoses in HIV-infected individuals in the combination antiretroviral therapy era, and to compare its effects in HIV-infected vs. uninfected individuals with similar demographic characteristics using data from a large prospective cohort of men who have sex with men .Cross-sectional analyses of baseline characteristics and prevalence of pulmonary diagnoses were stratified by HIV serostatus and marijuana smoking, and HIV serostatus, marijuana, and tobacco smoking, respectively. Marijuana smokers were defined as participants reporting ≥1 year of daily or weekly use in follow-up; tobacco smokers were participants reporting any tobacco smoking in follow-up. Cox proportional hazard models were used to assess the association between marijuana smoking and first incident infectious pulmonary diagnosis, and chronic bronchitis, which comprised the majority of noninfectious diagnoses. Participants were followed until their first incident diagnosis, loss to follow-up, death, or end of study in 2014, whichever came first. For each outcome, models were fit separately for HIV+ and HIV− participants using two time-varying variables for marijuana and tobacco smoking: Model 1, current marijuana smoking and prior two-year average tobacco smoking,and Model 2, prior two-year average marijuana smoking and prior two year average tobacco smoking.
Models were adjusted by time-invariant baseline education status, race, and baseline calendar period to adjust for potential differences in participant composition between MACS recruitment periods. Models for HIV+ participants were also adjusted by time-varying CD4 T cell count, and by time-varying self-reported ART use in models of infectious diagnoses; 65 participants with no CD4 data during follow-up were omitted from these analyses. Age was used as the time variable in all models.Continuous variables summarizing marijuana and tobacco smoking were right skewed and therefore square-root transformed and reported as back transformed estimates in their original scale. Additional analyses were performed with models for HIV+ participants using: a) visits restricted to CD4 count ≥200 cells/μl, b) time-varying cumulative exposures of marijuana and tobacco smoking in the prior ten years,and c) visits restricted to HIV viral load b400 copies/ml. Cumulative hazard curves estimating risk differences by marijuana and tobacco smoking were constructed by holding other model covariates at their mean values. Generalized estimating equation logistic regression models were used to assess the association between marijuana smoking and infectious pulmonary diagnoses while including repeated measures and potentially multiple diagnoses within the same individual. To minimize the potential for duplicate reports of a single diagnosis, only the first of identical diagnoses at consecutive visits were included. Exposure and adjustment variables were the same as for Cox models, except time varying, continuous duration in study, and baseline age were included. All analyses were performed with R .Among HIV+ participants, CD4 T cell count, HIV viral load, or ART use did not differ between marijuana smokers and non-smokers.
Marijuana smokers were more likely to report one or more infectious or non-infectious pulmonary diagnosis compared to nonsmokers during follow-up among HIV+ participants ,while there was no association between marijuana smoking and either diagnosis among HIV− participants.Given the high prevalence of tobacco smoking among participants, frequencies of diagnoses were determined after stratifying participants by marijuana and tobacco smoking during follow-up. The proportion of HIV+ participants with one or more infectious pulmonary diagnosis was elevated among marijuana smokers and participants reporting any tobacco smoking in follow-up. Influenza and viral pneumonia and other pneumonias were among diagnoses occurring more frequently in marijuana smokers: other pneumonias were reported in 22% and 23·9% of participants smoking marijuana only, or both marijuana and tobacco, respectively, compared to non-smokers.Among HIV− participants, infectious diagnoses were more prevalent in individuals smoking both marijuana and tobacco, and non-infectious diagnoses were elevated among tobacco but not marijuana smokers. The majority of diagnoses were assessed from ICD coding data, while chronic bronchitis diagnoses were predominantly assessed from self report.When modeled as a continuous variable, each 10 days/month increase in marijuana smoking in the prior two year period was associated with a 6% increased risk of infectious pulmonary diagnosis.CD4 T cell count b200 vs. ≥350 cells/μl was most strongly associated with infectious pulmonary diagnosis risk in both models,and therefore, additional models were fit restricted to 17,529 person-visits with CD4 T cell count ≥200 cells/μl of 19,009 total person-visits.
Both current daily or weekly and prior two-year average marijuana smoking remained associated with increased risk of infectious pulmonary diagnoses in these adjusted models.Smoking ≥1/2 vs. 0 packs of tobacco/day was strongly associated with increased risk of infectious pulmonary diagnoses,while low CD4 count remained associated with a higher risk of infectious pulmonary diagnoses. Cumulative estimates of marijuana and tobacco smoking in the prior ten years remained associated with infectious pulmonary diagnoses in additional models adjusted for the same factors.Additionally, the association between daily or weekly marijuana smoking and infectious pulmonary diagnoses remained significant in models restricted to 14,666 person-visits with suppressed HIV viral load.There were no associations between marijuana smoking and infectious pulmonary diagnoses in HIV− participants, while tobacco smoking showed a strong association.The association between marijuana smoking and infectious pulmonary diagnoses remained significant in GEE logistic regression models using longitudinal data, which allowed for multiple diagnoses within the same individual.A total of 516 diagnoses were reported for 421 of 1287 total participants at 22,694 person-visits with ≥200 CD4 T cells/μl.There was no association between marijuana smoking and infectious pulmonary diagnoses in HIV− individuals. Cox proportional hazard models of non-infectious pulmonary diagnoses were limited to chronic bronchitis, given these diagnoses comprised the majority of events. Current daily or weekly marijuana smoking was associated with increased risk of chronic bronchitis among HIV+ participants, while there was a marginal association between marijuana smoking in the prior two years and chronic bronchitis in these models.CD4 T cell count and tobacco smoking in the prior two years were more strongly associated with chronic bronchitis risk compared to marijuana smoking.Cumulative estimates of marijuana and tobacco smoking in the prior ten years showed similar associations with chronic bronchitis in additional models adjusted for the same factors.There were no associations between marijuana smoking and chronic bronchitis in HIV− participants, although tobacco smoking was strongly associated with this outcome.There were no significant interactions between marijuana and tobacco smoking in any multivariable model tested for HIV+ participants, indicating independent effects of these factors, and no significant interactions between marijuana smoking and time in GEE analyses of repeated infectious pulmonary events, indicating no evidence for changing risk level over the study duration.
Imputation of missing observations by last value carried forward was validated with Cox model estimates pooled from ten data-sets using predictive mean matching multiple imputation, which demonstrated similar associations between daily or weekly marijuana smoking and infectious pulmonary diagnoses and chronic bronchitis for HIV+ participants.Cumulative hazard curves from multivariable Cox models are shown in Fig. 2, which predicts highest hazard rates for both infectious pulmonary diagnoses and chronic bronchitis among HIV+ participants smoking both cannabis grow lights and tobacco.In this prospective study of 2704 MSM contributing over 53,000 person-visits, marijuana smoking was associated with increased risk of both infectious and non-infectious pulmonary diagnoses among 1352 HIV-infected participants independent of tobacco smoking, CD4 count, ART adherence, and demographic factors. To our knowledge, this study is the largest investigation of smoked marijuana and pulmonary diagnoses in HIV-infected individuals to date. In multi-variable Cox models, current daily or weekly marijuana smoking and increased average marijuana smoking over the prior two years were associated with elevated risk of infectious pulmonary diagnoses in HIV+ participants; these results were confirmed in GEE logistic regression models allowing for repeated diagnoses within the same individual. Current marijuana smoking was also associated with increased risk of chronic bronchitis in multi-variable Cox models, while increased average marijuana smoking in the prior two years was marginally associated with these outcomes.Marijuana and tobacco smoking were independent risk factors in Cox models, and the predicted additive risk of smoking both substances was markedly higher than smoking either substance alone. In contrast, there were no significant associations between marijuana use and infectious pulmonary diagnoses or chronic bronchitis in multi-variable models of 1352 HIV− participants adjusted by tobacco smoking, age, race, education, and calendar period. These findings confirm the known association between HIV infection and increased prevalence of pulmonary disease, and provide evidence that HIV-infected individuals may be more vulnerable to marijuana’s effects on lung disease compared to uninfected participants with similar exposures.
In contrast to the well-studied effects of tobacco smoking, the effects of marijuana smoking on lung function and health in the general population remain unclear, though multiple studies reported an increased prevalence of chronic respiratory symptoms in frequent marijuana smokers. Spirometric forced expiratory volume,forced vital capacity,and their ratio are measures of airflow obstruction; FEV1/FVC is reduced in tobacco smokers compared to non-smokers, while studies of marijuana smokers have reported conflicting results. Likewise, a cross-sectional study of pulmonary function among HIV-infected recreational drug users in the U.S. reported no association between marijuana smoking and airflow obstruction or radiographic emphysema. In the U.S., marijuana remains an illegal Schedule 1 substance nationally, and is not regulated by the Food and Drug Administration. Marijuana contains substantial variation in the quantity of psychoactive delta-9 tetrahydrocannabinol and other combustible components, complicating systematic comparisons based on observational studies. While marijuana and tobacco smoke contain many of the same toxic constituents, previous studies reported higher concentrations of hydrogen cyanide, ammonia, and polycyclic aromatic hydrocarbons in marijuana smoke, and higher concentrations of blood carboxyhemoglobin concentrations, greater depth of inhalation, and greater puff volume in marijuana compared to tobacco smokers. Pulmonary disease risk may be increased in HIV-infected vs. uninfected individuals due to HIV-specific factors including lung immune cell depletion and dysfunction, persistent immune cell activation, systemic inflammation, respiratory microbiome alterations, and oxidative stress, or a combination of these effects with modifiable risk factors including tobacco smoking. Previous studies linked marijuana smoke with alveolar macrophage dysfunction in both humans and mouse models, and a potential additive risk of marijuana smoking and HIV disease may explain the increased prevalence of infectious pulmonary diagnoses in our adjusted analyses. The association between HIV infection, low CD4 T cell count, and increased risk of infectious and non-infectious pulmonary disease has been previously reported, and was the strongest predictor of infectious pulmonary diagnoses in HIV+ participants in our study.