Category Archives: HIV/AIDS

Marijuana use and viral suppression in persons receiving medical care for HIV-infection.

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“Marijuana use is common among persons living with HIV (PLWH), but studies on its effect on HIV clinical outcomes are limited. We determined the association between marijuana use and HIV viral suppression among PLWH.

Of the 1,902 PLWH receiving antiretroviral therapy, completed an interview, and had a linked MRA, 20% reported marijuana use (13% less than daily and 7% daily use) and 73% achieved durable viral suppression. In multivariable analysis, marijuana use was not significantly associated with durable viral suppression in daily [Adjusted Odds Ratio (AOR): 0.87, 95% confidence interval (CI): 0.58, 1.33] or in less than daily [AOR: 0.83, 95% CI: 0.51, 1.37] users as compared to non-users when adjusting for sociodemographic factors, time since HIV diagnosis, depressive symptoms, alcohol, cigarette and other substance use.

CONCLUSION:

In this sample of PLWH receiving medical care in Florida, there was no statistically significant association between marijuana use and viral suppression. However, as the limits of the confidence intervals include effects that may be considered to be clinically important, there is a need for additional evidence from other samples and settings that include more marijuana users.”

http://www.ncbi.nlm.nih.gov/pubmed/27398989

Pharmacologic and non-pharmacologic treatments for chronic pain in individuals with HIV: a systematic review.

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“Chronic pain occurs in as many as 85% of individuals with HIV and is associated with substantial functional impairment. Little guidance is available for HIV providers seeking to address their patients’ chronic pain. We conducted a systematic review to identify clinical trials and observational studies that examined the impact of pharmacologic or non-pharmacologic interventions on pain and/or functional outcomes among HIV-infected individuals with chronic pain in high-development countries. Eleven studies met inclusion criteria and were mostly low or very low quality. Seven examined pharmacologic interventions (gabapentin, pregabalin, capsaicin, analgesics including opioids) and four examined non-pharmacologic interventions (cognitive behavioral therapy, self-hypnosis, smoked cannabis). The only controlled studies with positive results were of capsaicin and cannabis, and had short-term follow-up (≤12 weeks). Among the seven studies of pharmacologic interventions, five had substantial pharmaceutical industry sponsorship. These findings highlight several important gaps in the HIV/chronic pain literature that require further research.”

http://www.ncbi.nlm.nih.gov/pubmed/27267445

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

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“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

No significant effect of cannabis use on the count and percentage of circulating CD4 T-cells in HIV-HCV co-infected patients (ANRS CO13-HEPAVIH French cohort).

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“Despite cannabis use being very common in patients co-infected with HIV and hepatitis C virus (HCV), its effect on these patients’ immune systems remains undocumented.

Documenting the potential effect of cannabis use on HIV immunological markers would help caregivers make more targeted health recommendations to co-infected patients.

We performed a longitudinal analysis of the relationship betweencannabis use and peripheral blood CD4 T-cell measures in co-infected patients receiving antiretroviral therapy.

Findings show no evidence for a negative effect of cannabis use on circulating CD4 T-cell counts/percentages in HIV-HCV co-infected patients.”

http://www.ncbi.nlm.nih.gov/pubmed/27073179

http://www.thctotalhealthcare.com/category/hivaids/

Cannabinoids Occlude the HIV-1 Tat-Induced Decrease in GABAergic Neurotransmission in Prefrontal Cortex Slices.

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“In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is now considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND).

Endocannabinoids exhibit neuroprotective and anti-inflammatory properties in several central nervous system (CNS) disease models, but their effects in HAND are poorly understood.

Results indicated a Tat-induced decrease in GABAergic neurotransmission, which was occluded by cannabinoids via a CB1R-related mechanism.

Understanding the relationship between Tat toxicity and endocannabinoid signaling has the potential to identify novel therapeutic interventions to benefit individuals suffering from HAND and other cognitive impairments.”

http://www.ncbi.nlm.nih.gov/pubmed/26993829

http://www.thctotalhealthcare.com/category/hivaids/

Longitudinal examination of the intestinal lamina propria cellular compartment of SIV-infected rhesus macaques provides broader and deeper insights into the link between aberrant microRNA expression and persistent immune activation.

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“Persistent gastrointestinal tract (GI) disease/inflammation is a cardinal feature of HIV/SIV infection. Increasing evidence points to a critical role for microRNAs (miRNAs) in controlling several aspects of the immune/inflammatory response. Here, we show significant dysregulation of miRNA expression exclusively in the intestinal lamina propria cellular compartment through the course of SIV infection. Specifically, the study identified miRNA signatures associated with key pathogenic events such as viral replication, T-cell activation and microbial translocation. The T-cell enriched miR-150 showed significant downregulation throughout SIV infection and was confirmed to target IRAK1 (Interleukin-1 receptor 1 kinase), a critical signal-transducing component of the IL-1 receptor and TLR signaling pathways. Reduced miR-150 expression was associated with markedly elevated IRAK1 expression in the intestines of chronically SIV-infected macaques. Finally, delta-9 -tetrahydrocannabinol mediated blockade of CD8+ T cell activation in vitro significantly inhibited miR-150 downregulation and IRAK1 upregulation suggesting its potential for targeted immune modulation in HIV infection.”

http://www.ncbi.nlm.nih.gov/pubmed/26937033

Medicinal cannabis.

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“A number of therapeutic uses of cannabis and its derivatives have been postulated from preclinical investigations.

Possible clinical indications include spasticity and pain in multiple sclerosis, cancer-associated nausea and vomiting, cancer pain and HIV neuropathy.

Controversies lie in how to produce, supply and administer cannabinoid products.

Introduction of cannabinoids therapeutically should be supported by a regulatory and educational framework that minimises the risk of harm to patients and the community.

The Regulator of Medicinal Cannabis Bill 2014 is under consideration in Australia to address this.

Nabiximols is the only cannabinoid on the Australian Register of Therapeutic Goods at present, although cannabidiol has been recommended for inclusion in Schedule 4.”

http://www.ncbi.nlm.nih.gov/pubmed/26843715

“There is some evidence of therapeutic benefit for cannabis products in defined patient populations.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674028/

Marijuana Use is Not Associated with Cervical Human Papillomavirus Natural History or Cervical Neoplasia in HIV-Seropositive or HIV-Seronegative Women

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“Laboratory data suggest that marijuana could have an immunomodulatory effect.

Little is known, however, regarding the effects of marijuana use on cervical HPV or neoplasia. Therefore, we studied the natural history (i.e., prevalence, incident detection, clearance/persistence) of cervical HPV and cervical neoplasia (i.e., squamous intraepithelial lesions; SIL) in a large prospective cohort of 2,584 HIV-seropositive and 915 HIV-seronegative women.

No positive associations were observed between use of marijuana, and either cervical HPV infection or SIL. The findings were similar among HIV-seropositive and HIV-seronegative women, and in tobacco smokers and nonsmokers. These data suggest that marijuana use does not increase the burden of cervical HPV infection or SIL.

In summary, our investigation found no positive associations between marijuana use and cervical HPV or SIL. These findings are comforting given the high prevalence of marijuana use in HIV-seropositive and other populations…”

http://cebp.aacrjournals.org/content/19/3/869.full

Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC).

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“During human immunodeficiency virus (HIV) infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role.

For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages.

Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells (MDDC).

Our results show a differential effect of alcohol and cannabinoids, which may provide insights into the divergent inflammatory role of alcohol and cannabinoids to modulate MDDC function in the context of HIV infection.”

http://www.ncbi.nlm.nih.gov/pubmed/26733986

http://www.thctotalhealthcare.com/category/hivaids/