Description
Human immunodeficiency virus (HIV) is a lentivirus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk. Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells. The four major routes of transmission are unsafe sex, contaminated needles, breast milk, and transmission from an infected mother to her baby at birth (Vertical transmission). Screening of blood products for HIV has largely eliminated transmission through blood transfusions or infected blood products in the developed world.

HIV infection in humans is considered pandemic by the World Health Organization (WHO). From its discovery in 1981 to 2006, AIDS killed more than 25 million people. HIV infects about 0.6% of the world's population. In 2005 alone, AIDS claimed an estimated 2.4–3.3 million lives, of which more than 570,000 were children. A third of these deaths are occurring in sub-Saharan Africa, retarding economic growth and increasing poverty. According to current estimates, HIV is set to infect 90 million people in Africa, resulting in a minimum estimate of 18 million orphans. Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but routine access to antiretroviral medication is not available in all countries.

HIV infects primarily vital cells in the human immune system such as helper T cells (to be specific, CD4+ T cells), macrophages, and dendritic cells. HIV infection leads to low levels of CD4+ T cells through three main mechanisms: First, direct viral killing of infected cells; second, increased rates of apoptosis in infected cells; and third, killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections.

Most people infected with HIV eventually develop AIDS. These individuals mostly die from opportunistic infections or malignancies associated with the progressive failure of the immune system. HIV progresses to AIDS at a variable rate affected by viral, host, and environmental factors; HIV-specific treatment delays this process. Most will progress to AIDS within 10 years of HIV infection: some will have progressed much sooner, and some will take much longer. Treatment with anti-retrovirals increases the life expectancy of people infected with HIV. Even after HIV has progressed to diagnosable AIDS, the average survival time with antiretroviral therapy was estimated to be more than 5 years as of 2005. Without antiretroviral therapy, someone who has AIDS typically dies within a year.

The Cannabis Science™

J Immunol. 2008 Nov 1;181(9):6406-16.

Cannabinoids Inhibit HIV-1 Gp120-Mediated Insults in Brain Microvascular Endothelial Cells.

Lu TS, Avraham HK, Seng S, Tachado SD, Koziel H, Makriyannis A, Avraham S.

Division of Experimental Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.

HIV-1 infection has significant effect on the immune system as well as on the nervous system. Breakdown of the blood-brain barrier (BBB) is frequently observed in patients with HIV-associated dementia (HAD) despite lack of productive infection of human brain microvascular endothelial cells (HBMEC). Cellular products and viral proteins secreted by HIV-1 infected cells, such as the HIV-1 Gp120 envelope glycoprotein, play important roles in BBB impairment and HIV-associated dementia development. HBMEC are a major component of the BBB.

Using cocultures of HBMEC and human astrocytes as a model system for human BBB as well as in vivo model, we show for the first time that cannabinoid agonists inhibited HIV-1 Gp120-induced calcium influx mediated by substance P and significantly decreased the permeability of HBMEC as well as prevented tight junction protein down-regulation of ZO-1, claudin-5, and JAM-1 in HBMEC.

Furthermore, cannabinoid agonists inhibited the transmigration of human monocytes across the BBB and blocked the BBB permeability in vivo. These results demonstrate that cannabinoid agonists are able to restore the integrity of HBMEC and the BBB following insults by HIV-1 Gp120. These studies may lead to better strategies for treatment modalities targeted to the BBB following HIV-1 infection of the brain based on cannabinoid pharmacotherapies.

PMID: 18941231 [PubMed - indexed for MEDLINE]

Evaluation of Oral Cannabinoid-Containing Medications for the Management of Interferon and Ribavirin-Induced Anorexia, Nausea and Weight Loss in Patients Treated for Chronic Hepatitis C Virus.

OBJECTIVES: The systemic and cognitive side effects of hepatitis C virus (HCV) therapy may be incapacitating, necessitating dose reductions or abandonment of therapy. Oral cannabinoid-containing medications (OCs) ameliorate chemotherapy-induced nausea and vomiting, as well as AIDS wasting syndrome. The efficacy of OCs in managing HCV treatment-related side effects is unknown.

METHODS: All patients who initiated interferon-ribavirin therapy at The Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario) between August 2003 and January 2007 were identified using a computerized clinical database. The baseline characteristics of OC recipients were compared with those of nonrecipients. The treatment-related side effect response to OC was assessed by c2 analysis. The key therapeutic outcomes related to weight, interferon dose reduction and treatment outcomes were assessed by Student's t test and c2 analysis.

RESULTS: Twenty-five of 191 patients (13%) initiated OC use. Recipients had similar characteristics to nonrecipients, aside from prior marijuana smoking history (24% versus 10%, respectively; P=0.04). The median time to OC initiation was seven weeks. The most common indications for initiation of OC were anorexia (72%) and nausea (32%). Sixty-four per cent of all patients who received OC experienced subjective improvement in symptoms. The median weight loss before OC initiation was 4.5 kg. A trend toward greater median weight loss was noted at week 4 in patients eventually initiating OC use (-1.4 kg), compared with those who did not (-1.0 kg). Weight loss stabilized one month after OC initiation (median 0.5 kg additional loss). Interferon dose reductions were rare and did not differ by OC use (8% of OC recipients versus 5% of nonrecipients). The proportions of patients completing a full course of HCV therapy and achieving a sustained virological response were greater in OC recipients.

CONCLUSIONS: The present retrospective cohort analysis found that OC use is often effective in managing HCV treatment-related symptoms that contribute to weight loss, and may stabilize weight decline once initiated.

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Cannabis as Medicine: Time for the Phoenix to Rise?

Since 1971 British doctors have been barred from prescribing cannabis under the Misuse of Drugs Act. Many otherwise law abiding people have subsequently thought it worthwhile to expose themselves to the risk, inconvenience, and expense of obtaining illegally a drug they believe can ease symptoms inadequately controlled by conventional medicines. Patients have told me how effective cannabis can be in relieving aches and pains, numbing the symptoms of opiate withdrawal, improving sleep, reducing anxiety, and alleviating the vomiting, ano­rexia, and depression associated with AIDS related dis­orders. Anecdotes such as these are all very well, but is there any scientific evidence that cannabis has real therapeutic value?

The BMA has addressed this question with an excellent report, which begins by reviewing the pharmacology. Only a few of the 60 or so chemicals unique to Cannabis sativa (cannabinoids) have so far been studied, the best known of which is the main psy­choactive ingredient, δ-9­-tetrahydrocannabinol (THC). Specific cannabinoid receptors in the brain and in spleen macrophages, and naturally occurring sub­stances which bind to these (anandamides), have been identified in recent years. These findings open the door to developing novel agents for therapeutic use or exploring the physiological role of the anandamide system—which may be concerned with mood, memory and cognition, perception, movement, coordination, sleep, thermoregulation, appetite, and immune response.

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Nabilone as eEffective Therapy for Intractable Nausea and Vomiting in AIDS

Nabilone is a synthetic cannabinoid (Ward & Holmes, 1985) with powerful anti-emetic properties. In the U.K. at the present time the only licensed indication for its usage is in the control of nausea and vomiting resulting from the administration of cytotoxic chemotherapeutic agents used in the treatment of neoplastic disease (ABPI, 1989).

A 52 year old bisexual HIV-seropositive man who had developed a cryptosporidial infection of his gastrointestinal tract was recently treated in the Infectious Diseases unit. He had originally been diagnosed as having the acquired immune deficiency syndrome (AIDS) in April 1988, following a bout of Pneumocystis carinii pneumonia. The cryptosporidial infection led to the development of intractable nausea and vomiting which in turn severely compromised the patient's ability to maintain a satisfactory enteral nutritional input. Furthermore it proved impossible to treat his underlying cryptosporidiosis (no reliable anti-cryptosporidial drug has as yet been discovered) as well as to control his gastrointestinal symptoms with conventional agents such as prochlorperazine, cyclizine, domperidone and high-dose intravenous infusions of metoclopramide. In view of the severe distress sustained by the patient, he was commenced on oral nabilone 1 mg twice daily; the therapeutic response was remarkably successful, resulting in complete cessation of the patient's nausea and vomiting, which made the patient feel more comfortable generally. The patient was maintained on nabilone for 4 days, the only side effect being a degree of drowsiness which the patient found acceptable prior to the terminal stages of his illness. He ultimately died of a probable septicaemia.

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