The Centre of Molecular Biology of the CNRS in Orléans has developed for many years an expertise concerning apoptosis via the discovery of the GALIG gene. This pro-apoptotic gene produces two proteins, one of which, cytogaligin, interacts with several proteins involved in autophagy.~Recent translational research conducted jointly by the CNRS and CHR Orléans teams have shown that PBMC from HIV-infected patients who have been on effective cART for at least 4 years show changes in the expression of certain genes involved in autophagy (BECN1, GABARAPL1, MAP1LC3B and GALIG). Gomez-Mora et al. also reported a decrease in autophagic function in CD4+ T cells of patients, with the impairment of autophagy being more important as the reconstitution of the CD4+ T compartment is incomplete. Thus, autophagy defects are more pronounced in patients whose CD4 T cell count remains low, suggesting a link between autophagy and CD4 T cell depletion.In summary, even after prolonged virological control and apparent immune reconstitution, PLWH (people living with HIV) exhibit deregulation of genes involved in autophagy.~In the simian model, Δ9-tetrahydrocannabinol (Δ9-THC) cannabinoids would reduce inflammation associated with intestinal tissues, but also SIV viral load and mortality in males only. A recent review points to the potential benefit of cannabinoids on inflammation in the context of HIV. PLHIV who regularly use cannabis, and therefore potentially exposed to Δ9-THC and cannabidiol (CBD), have been the subject of a significant literature. Thus, it has been reported that in these patients, compared to non-consumers, there is a greater reduction in the HIV reservoir (HIV-DNA), a decrease in activated monocytes, the latter being linked to inflammation, as well as a reduced activation of CD4+ and CD8+ lymphocytes.~A first analysis is based on 6 HIV+ patients virologically controlled for at least 4 years, having absorbed, as a dietary supplement, for 4 weeks a dose of 30 mg x2 per day of CBD duly controlled pharmacologically (Δ9-THC dosage < 0.1%) and having declared not to use drugs. We were able to note by discriminant factor analysis (DFA):~a significant change in the expression of genes involved in autophagy. Their activation profile of genes involved in autophagy is no longer identical to that of virologically controlled HIV+ patients who did not take CBD.~a profile of serum inflammatory cytokines that is close to the profile of HIV-negative individuals, but different from that of PLWHIV who have not consumed CBD.~Thus, CBD, which has no psychotropic effect, could have beneficial effects on HIV patients by reducing cellular senescence, inflammation and their consequences in terms of co-morbidities as well as the level of HIV reservoirs through an apoptotic phenomenon of cells hosting HIV in a quiescent state. Among the molecules present in the plant and in particular the species Cannabis sativa L., can be present the CBD, the Δ9 THC and a multitude of terpenes without psychotropic effects, which would be responsible for an effect of entourage. Studies argue for a synergistic effect of these molecules to lead to the suspected effects.
Autophagy and apoptosis are natural cellular mechanisms which consist for the first in a recycling and elimination process of potentially toxic cellular waste, and for the second in a process of cellular suicide when it becomes abnormal and not repairable, notably by autophagy. A deficit in autophagic function at the cellular level can lead to chronic inflammation and accelerated cellular senescence. Apoptosis is a beneficial phenomenon because it eliminates abnormal cells that could endanger the organism if it survives (e.g. karyotypic atypia). Uncontrolled, it can be deleterious if apoptosis is hypo or hyperactive.