Benefits of cannabis use for metabolic disorders and survival in people living with HIV with or without hepatitis C co-infection

We read with great interest the Editorial review by Costiniuk and Jenabian [1] published recently in AIDS and would like to bring additional evidence about the benefits of cannabinoids in people living with HIV (PLWH), including patients with hepatitis C virus (HCV) co-infection. As highlighted in the review, cannabis use was not associated with lower CD4+ count in the French nationwide multicenter ANRS CO13 HEPAVIH cohort of HIV/HCV co-infected patients, after adjustment for baseline CD4+ count and other clinical variables, suggesting that cannabinoids contained in cannabis do not have a negative effect on circulating CD4+ T cells [2]. In another multicenter cohort in Canada, cannabis use was not associated with liver fibrosis or cirrhosis progression among co-infected patients who did not have significant fibrosis or end-stage liver disease at baseline [3]. Similarly, data from the largest US cohort of HIV-infected women showed no significant association between duration or frequency of cannabis use and progression to significant fibrosis among HIV/HCV co-infected women [4]. In France, another study based on data from the ANRS CO13 HEPAVIH cohort showed no significant relationship between cannabis use and liver stiffness (based on transient elastography measures) [5], the latter being associated with increased overall and liver-related mortality in the cohort [6]. Moreover, a systematic review with meta-analysis found no association between cannabis use and liver fibrosis progression among HIV/HCV co-infected patients with chronic liver disease [7]. All of these findings are especially relevant given that liver-related complications are one of the main causes of morbidity and mortality in the HIV/HCV co-infected population [8]. Furthermore, in a previous longitudinal study based on data from the HEPAVIH cohort, cannabis use (whether occasional, regular, or daily) was significantly associated with lower risk of insulin resistance, after adjustment for other correlates and confounders [9]. This result is particularly important given that HIV/HCV co-infected individuals have a higher risk of insulin resistance and diabetes, which in turn increases their risk of liver damage, affecting morbidity and mortality [10]. In addition, this association was confirmed in HCV mono-infected patients participating in the French ANRS CO22 HEPATHER cohort, where cannabis use was independently associated with a lower risk of diabetes [11]. The association found between daily cannabis use and a 36% reduction in the risk of liver steatosis among HIV/HCV co-infected individuals in the ANRS CO13 HEPAVIH cohort (after adjusting for BMI, antiretroviral exposure and hazardous alcohol consumption) [12,13] seems to confirm the beneficial effects of cannabis on the metabolic system in this population. This result reflects those found in the general US population, where cannabis users exhibited lower prevalence of nonalcoholic fatty liver disease, independently of known metabolic risk factors [14,15]. In addition, in another US population-based study, cannabis use was associated with reduced incidence of progressive stages of advanced liver disease – including steatosis, steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma – among patients with abusive alcohol use [16]. Likewise, cannabis use was not identified as a risk factor for overall mortality among PLWH with or without HCV co-infection in both US [17] and French cohorts [18], whereas tobacco smoking was a main predictor of overall mortality risk. Interestingly, a competing risk modelling approach using data from the ANRS CO13 HEPAVIH cohort revealed that regular or daily cannabis use was associated with reduced HCV-related mortality by 72%, independently of tobacco smoking, the latter remaining a significant risk factor [19]. Together with the results reported in Costiniuk and Jenabian's Editorial review [1], these additional data suggest that medical cannabinoids may be of specific benefit to PLWH co-infected with HCV and those who are not. For some patients in these two populations, cannabis use is an act of self-medication. It can help manage HIV-related inflammation and, possibly, lessen the effects of a dysfunctioning endocannabinoid system [20] and its repercussions on other systems, in particular, those leading to metabolic disorders. Although further research on the health effects of cannabis use in PLWH with or without HCV co-infection is needed, improving access to controlled cannabinoid-based therapies and implementing risk reduction interventions to reduce smoking habits and promote a healthier lifestyle constitute priority actions, and have the potential to add years to life and life to years in PLWH with or without HCV co-infection. In conclusion, we share Costiniuk and Jenabian's opinion that clinical investigations are important to evaluate the efficacy and safety of cannabis-based therapies aiming to control morbidity and to reduce mortality in PLWH, particularly among HIV/HCV co-infected individuals, within the wider context of supporting healthcare interventions through innovative public policies. Acknowledgements Our thanks to Jude Sweeney for the English revision and editing of this manuscript. Funding: Part of this work was supported by the French National Agency for Research on Aids and Viral Hepatitis (ANRS: France Recherche Nord & sud Sida-hiv Hépatites), with the participation of Abbott France, Glaxo-Smith-Kline, Roche, Schering-Plough, BMS, Merck-Serono. Conflicts of interest There are no conflicts of interest.

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