Kenyan part of team edging closer to finding HIV cure

Ten years ago, a young Kenyan student left the country for further studies in the US with just a degree in chemistry.

When he sat down with the Nation during his first return since he left, one could hardly deduce that the young man seated calmly at the reception had just joined a pool of niche scientists, in whom the world hinges its hopes for a cure for HIV.

ELIMINATE VIRUS

At 37, Benson Edagwa is not only a principal author or major contributor to more than 30 published biomedical papers in peer-reviewed journals, but is also listed as an inventor on 12 US patent applications.

But his most popular work revolves around a recently published research study, which shows that a cure for HIV could be on the horizon.

Three weeks ago, a journal, Nature Communications, reported that Prof Edagwa, and a team of researchers, had successfully eliminated HIV in living mice.

“For me, the driving force behind my focus on finding a treatment for HIV is personal. I’ve lost friends and family to the disease, and my country, Kenya, is still reeling from the disease,” he said.

With an estimated 19.6 million people in East and Southern Africa — 1.5 million Kenyans — living with HIV and about 380,000 recorded deaths, the journey to getting a cure seems to be nearing the homestretch.

Unless treated, HIV can turn into Aids that damages the immune system.

Prof Edagwa did an undergraduate degree in Chemistry at Moi University’s Chepkoilel Campus before enrolling into a master’s programme and later completing a PhD at the Louisiana State University (LSU) in 2012. He accepted a position at the University of Nebraska Medical Centre (UNMC) the same year.

In a study involving 29 mice, in some of the animals, the team used a combination of gene-editing technology (CRISPR) and a therapeutic treatment called Laser Art to erase HIV DNA from the genes of animals in what has been considered unprecedented.

But if it were not for Prof Edagwa’s wife, Dr Teresa Mutahi, this study would probably not have been accomplished.

“You know, it is funny that this great success came from my desire to have peace at home. My wife constantly asked if I had completed the project, which I had to hide from my boss because for him, the idea seemed crazy,” recounts the assistant professor of pharmacology at UNMC.

“So I pursued the project to the end.”

DISMISSED FEAT

Five years down the line, Edagwa’s idea bore fruit and buy-in with his supervisor. When he first told his supervisor who is also an expert on HIV about the idea he had, his senior dismissed the feat as impossible.

But that did not discourage him. That evening when I got home, I told my wife, a biology professor, about it and she urged me to pursue it.

“Every day I got home she would ask for a progress report. Yet, at work, my boss wanted me to focus my attention on what he deemed better ideas. Oftentimes it’s impossible to please everyone so after weighing my options, I decided to have peace at home by concluding the research,” the father of two said.

So, he went back to the lab to work with students and if an idea worked in the laboratory, he would push it forward.

“Many discoveries are realised when you work with a diverse team which complements each other’s skills. Growing up, I neither attended the best schools nor did I get the best grades but I worked hard, was passionate and shared my observations,” he said. Prof Edagwa is the only chemist in the team of 27.

When he joined the team of mostly biologists, he wanted to shift focus from what the virus does to the body — “an area where a lot of work had been carried out, to understand for ways of stopping it altogether,” he said.

He took what is currently in the market and tapped into the knowledge and expertise of biologists and HIV experts to see how to improve the medicines.

"I assigned my Ph.D. students a number of projects which I monitored physically from the laboratory," he said.

When he started his research, he had collaborated with British multinational pharmaceutical company Glaxosmithkline who dropped off along the way.

“I had made a lot of headways and one day they just stopped the funding without any explanation. Now the U.S government is our funder.”

PENETRATE BODY

HIV is a virus spread through certain body fluids that attacks the body’s immune system, specifically the CD4 cells, often called T cells. Over time, HIV can destroy so many of these cells that the body can’t fight off infections and disease. These special cells help the immune system fight off infections. Untreated, HIV reduces the number of CD4 cells (T cells) in the body. This damage to the immune system makes it harder and harder for the body to fight off infections and opportunistic diseases like cancer.

He wanted to achieve two things: reduce the frequency of drug intake by patients and also completely eliminate the virus from the body by coming up with a drug that could penetrate into hard-to-reach areas in the body like the brain, the lymph nodes and even cells, something that standard ARVs do not do.

“By reaching these reservoirs, we have demonstrated that HIV is a curable disease. What we had in the past were prevention and treatment strategies,” he said.

However, it has been very difficult to cure the disease because of how fast the virus that causes HIV infection mutates into other strains. But it wasn’t an easy feat to achieve.

Modern antiretroviral treatment can already suppress HIV to the point that it has no impact on life expectancy, and even make it untransmittable.

“Currently available antiretroviral therapy (ARVs) medicines in the market only target the active form of the virus and not the dormant one. Therefore, we set out to look for a way of combat both strains of the virus.”

This is because HIV usually targets and alters the patient’s immune system, increasing their risk and impact to other infections and diseases. The virus also has two strains; an active and dormant strain. Current ARVs cannot eliminate the virus entirely but they suppress its replication. But if they are modified with Laser Art, they can overcome this obstacle, and reach those reservoirs.

Edagwa’s team modified an ARV to reach the spleen, bone marrow and brain, where HIV might be hiding. After several weeks, they used the gene-editing tool to cut out the DNA fragments where HIV was still clinging.

'PEAKS AND VALLEYS'

“You can only say that you have a cure for the virus if the treatment can combat both strains. Under normal circumstances, when a patient takes ARVs and stop, the disease usually comes back. So the first thing was to find a way in which if the patient stops taking the ARTs the virus will not resurface,” he went on.

During the research, we combined the two [LASER (ART) and CRISPR Cas-9] then monitored the mice under normal circumstances to see whether or not the virus duplicated itself. LASER ART is a medicine that can be administered as an injection once monthly or annually after which the body is able to sustain the drug in concentrations that “keeps the virus in check” for either a month or year before another dose is given. That was the first goal

The second one was to see if the drug was able to penetrate into hard-to-reach areas in the body like the brain, lymph nodes, and even cells. Standard ARVs do not penetrate these parts of the body where the virus hides.

“We then had to look at the side effects of the drug. The essence of taking daily doses of the ARTs medication is to maintain levels of the drugs in the body. This is because the levels of the drug, when taken orally, oscillate from high to low (peaks and valleys), thereby exposing the patient to the side effects.”

In the body Prof Edagwa went on, LASER ART remains at the desired level for a longer duration of time. It can be controlled to remain at one level for as long as you want. Since this drug is able to penetrate the virus’ reservoir, it is able to control the active strain of the virus.

“After taking care of the active strain, you go in with gene editing using CRISPR Cas-9, which is essential acts like a scissor guided by an enzyme to the part of the DNA where the virus is. The scissors then snip out the dormant form of the virus in our DNA. That is the only way one can claim to have cured HIV because it will have been completely removed from ones’ DNA.”