Researchers, HIV sanctuaries disinclined on HIV eradication

OPINION

By Dr. Majwala Meaud Major

As we commemorate the World AIDS Day, with a theme-Developing New HIV Prevention Options for Women- we should always be aware of the macroeconomic effects of HIV/AIDS in the world but most especially in Africa are substantial, and policies for dealing with them may be controversial-one is whether expensive antiretroviral drugs should be targeted at economically productive groups of people. Four million people died from AIDS in 2014, making it the world's fourth biggest cause of death, after heart disease, stroke, and acute lower respiratory infection.

Over 70% of the world's 40 million people living with HIV/AIDS are in Africa. Besides the human cost, HIV/AIDS is having profound effects on Africa's socio-economic and political development and hence its ability to cope with the pandemic.

While the impact of HIV/AIDS on people may be well documented, it has been much more difficult to observe the pandemic's effects on the African political economy as a whole or to assess how it might affect Africa's future development. Nevertheless Scientist, researchers and medical professionals have dedicated a lot of time and money on various inventions, innovations and research experiments to understand these broader causes and effects of the HIV/AIDS pandemic in order to form effective policy responses aimed at eradicating it. But what went wrong?

A goal-directed research sanctioned by the Global Healthcare & Education Initiative-Uganda Chapter (GHEI-Uganda)  focusing on the progress of HIV/AIDS prevention, control, treatment and positive living found out that the body has cellular, anatomical and microanatomical HIV viral compartments that are not necessarily reached by available pharmacological strategies.

However, some strategies have been developed in order to weaken viral persistence and, consequently, contribute to the eradication of the HIV. It is now a true story that the discovery of highly active antiretroviral therapy (HAART) has saved millions of people infected with the human immunodeficiency virus (HIV). However, complete virus eradication is not possible due to small reservoirs of latently infected immune cells.

These reservoirs are sanctuaries of undetected HIV-infected cells that produce active viral particles and can, therefore, be an obstacle for the eradication of HIV. We are yet to run the race to win on getting to the reality check about the eventual cure of the virus.

Nevertheless, almost all new infections occur from a single CCR5-tropic founder virus (an HIV virus that enters immune cells through their CCR5 receptors), but a CXCR4-tropic virus (a CXCR4 receptor-docking HIV virus) is reported in rare instances. Viral loads rise exponentially to high levels within one to three days, depleting around 50% of all CCR5+ memory CD4+ T cells (a type of immune cell that HIV uses to replicate) in an irreversible way.

Post-exposure prophylaxis with HAART can limit HIV replication by diminishing the size of the reservoirs and preserving the immune function. Some individuals are able to control viral replication even after treatment cessation (they are called as post-treatment controllers). It is believed that sixty to eighty years is the estimated time required to eradicate HIV based on available treatment with HAART! This viral persistence is associated with the cellular compartmentalization of HIV, suggesting that anatomical, micro anatomical and cellular locations are significant barriers to eradicating HIV.

Central memory CD4+ T cells are considered a stable and long-lasting reservoir of HIV because they have a low proliferation rate and relatively long half-life. Stem cell-like memory T cells expressing markers for CD45RA, CCR7, CD27 and CD62L receptors can be differentiated into central memory, effector memory or terminally differentiated T cells, and may represent a very stable and long-lived cellular compartment. Macrophages may be a viral reservoir in the presence of the accessory protein Vpx (a protein associated with HIV-2/SIV that can block host restriction).

According to Mr. Kasozi Dickson of GHEI-Uganda, the team leader of the research "the human body has also regions that can restrict the access of immune cells. The central nervous system (CNS) has an elevated HIV persistence since the virus can cross the blood-brain barrier by infected monocytes or macrophages.

HIV infects the microglia, among others, which is then not only able to produce viral particles, but also allows them to persist for several years. Its persistence in the CNS is potentiated due to the fact that not all antiretrovirals can cross the blood-brain barrier. The male genital tract is a sanctuary since HIV- or SIV-specific CD8+ T cells have been detected in the testis interstitial tissue, in the stroma of the epididymis, seminal vesicles, prostate and urethra, and within the epithelium of the epididymis, seminal vesicles and penile urethra. The adipose tissue also expresses HIV's entry receptors, such as CD4, CCR5 and CXCR4, and hosts CD4+ T cells containing latently integrated HIV".

It is possible that adiponectin impairs the cytotoxic activity provided by CD8+ T cells against HIV-infected CD4+ T cells. The B cell follicle within the lymph node is a key compartment because it is relatively deprived of CD8+ T cells which could recognize and kill virally-infected cells.

These cellular, anatomical and microanatomical viral sanctuaries are important barriers against an HIV cure. However, some strategies have been developed in order to weaken the viral persistence and, consequently, contribute to the eradication of the HIV.

The Case for Marijuana as HIV Medicine

Support for medicinal marijuana has reached an all-time high in the many parts of the world especially among the medical practitioners. With over 70 percent of the elite community in favor of the use of cannabis to lessen the effects of a large number of chronic medical conditions.

People with HIV have long realized that cannabis can ease many HIV-related conditions, including nausea, loss of appetite, depression, weight loss, and neuropathic pain. In addition to treating common symptoms of HIV and side effects of antiretroviral drugs, research indicates that cannabis may help fight HIV itself.

An increasing number of scientific studies, conducted at well-known institutions and published in prominent medical journals, are revealing antiviral effects of cannabis against HIV. These studies detail diverse approaches in measuring favorable effects that cannabis may have in slowing HIV disease progression.

As we tend to get to the conclusion in belief for this, THC in monkeys may lessen HIV's damage in the gut During primary infection HIV attacks the gut-associated lymphoid tissue (GALT), where a substantial amount of the immune system is located, hitting CD4 cells hard and early during this process. The initial damage done to GALT is believed to be essential to the progression of HIV disease.

A study funded by the National Institutes of Health and the National Institute on Drug Abuse of United States of America and published in AIDS Research and Human Retroviruses in 2014 found that THC, the best-known component of cannabis, had a positive effect on GALT in rhesus monkeys that were infected with SIV, the simian version of HIV, after 17 months of receiving THC.

Checking the monkeys five months later, researchers from the Louisiana State University Health Sciences Center found that THC produced a generalized decrease in viral load and tissue inflammation and increased production of disease-fighting CD4 and CD8 central memory T cells in GALT.

Finding a way of blocking HIV's entry

To this end, the effects of cannabis are a result of interactions between cannabinoids and receptors located on many cells, including macrophages (a tissue cell of the immune system) and CD4 cells called cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). Researchers at New York City's Mount Sinai School of Medicine published data in 2012 demonstrating that stimulation of CB2 with compounds called cannabinoid receptor agonists can block the signaling process between HIV and CXCR4, one of the main types of receptors that allow HIV to enter and infect a cell.

CXCR4 is used by HIV during advanced disease and allows for faster disease progression. By stimulating activation of CB2 with cannabinoid receptor antagonists, Mount Sinai researchers decreased the ability of HIV to infect cells that utilize CXCR4, reducing the frequency of infected cells by 30 to 60 percent.

The future of cannabis in HIV

Yes we are optimistic with the various research findings, many of the researchers are indisposed and loath about the final verdict on the total eradication of HIV, with reasons not given. Although Big Pharmacies are yet to make a serious commitment to the study of cannabis for the treatment of disease, many universities and a small number of biotech companies are investing in the research and development of cannabinoid-based medications.

One such company has taken an interest in cannabis and HIV. Cannabis Science is exploring the use of cannabinoids to treat Kaposi's sarcoma in people with HIV as well as a potential therapy directed at inhibiting the HIV protein Tat, which is key for viral replication and modulates the expression of genes that regulate a variety of cellular activities.

This would be revolutionary for people living with HIV, as chemotherapy, a primary treatment for Kaposi's sarcoma, is largely unavailable in Africa, which has the highest burden of the disease.

A cannabinoid-based antiviral would be cheaper than currently available drugs, greatly decreasing the cost of treating HIV and allowing for increased access to treatment for the nearly 7 million HIV patients around the world who need antiretroviral drugs but do not currently have access to them.

We need to work together for the common good.

The writer is the president of Sustainable World Initiative-East Africa.
E.mail: majormeaud@gmail.com