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When Will There Ever Be a Cure for HIV?

We’ve all read about AIDS and HIV, from the ongoing AIDS epidemic happening right here in the good ol’ U.S. of A, to the many countries of Africa (remember MBAs, Africa isn’t a country). Human Immunodeficiency Virus (HIV) is a Sexually Transmitted Disease (STD) shrouded in stigma, terror and prejudice. That’s because, unlike many other STDs like herpes, HIV can become lethal at its later stages of progression, during which patients can develop AIDS, or AutoImmune Disease Syndrome (AIDS). Sorry to toss the alphabet soup at you, but if you keep up, there might just be a nice prize at the end.

The virus can come in two flavors, HIV-1 and HIV-2, with HIV-1 making up 95 percent of all cases worldwide. Both are spread by blood-to-blood contact, sexual activity, and breast milk. There are also more interesting, less PG-13 combinations of those three that we won’t get into. When a person first acquires HIV, they’ll start to have symptoms that look like the flu for a few weeks. But after the body starts building immunity to the virus, there won’t be any noticeable symptoms at all for months, or even years, which makes treatment that much more difficult.

Global number of AIDS-related deaths, new HIV infections and people living with HIV from 1990 to 2015

HIV sucks

That’s because HIV is sneaky and likes to dig into immune cells, where the virus will hang out completely dormant. During times of stress, the virus will multiply, causing the host immune cells to burst and die. Just think of the classic chest-bursting scene from Aliens. Only in the final third stage of disease does an HIV patient start to notice severe symptoms, as their immune system, specifically T-cells or CD4 cells, gets slowly wiped out. This is the condition of AIDS, during which patients will contract a bunch of infectious diseases and will eventually die from them. HIV is some serious stuff.

A Market for a Cure

The market for an HIV cure could be extremely lucrative. More than 36.9 million people worldwide were living with HIV or AIDS in 2017, with another 1.8 million added to the roster that year, according to the UNAIDS. Some additional facts from the website: About 70 percent of those infected are living in Africa alone, while an estimated 1.1 million Americans are currently infected with HIV with a whopping 1 in 7 not even knowing that they have it. Currently, the basic cost of anti-retroviral treatments – just to keep the virus under control – averages $20,000 per year. Some quick back-of-the-napkin math tells us that’s nearly $800 billion per year for everyone infected with HIV.  

Issues with HIV Treatments

The virus lives inside immune cells, and so the body has a hard time looking for it. And since the virus also wreaks havoc on the host immune system, a patient will continue to have a tough time fighting the virus as T-cell counts continue to be depleted. These two features have made searching for an HIV cure a pain in the you-know-what. While HIV is currently incurable, fewer patients these days have to live with the advanced stages of full-blown AIDS. Just look at Magic Johnson.

The progression of HIV.

The progression of HIV. Credit: NIH

A major advancement came in the form of anti-retroviral cocktails developed in 1997 that have since become the gold standard for treatment. But the basic cost of these therapies rack up and can still lead to HIV remission. And further research and development into HIV vaccines has been halted by some major players. Swiss pharmaceutical company and developer of HIV treatments Roche announced in 2008 that it would no longer pursue active research into new vaccines after concluding pre-clinical trials on key leads. The National Institute of Allergy and Infectious Disease stopped clinical trials on the HVTN 505 vaccine in 2013; the vaccine simply didn’t show any change in HIV viral count. And the truth is that all AIDS vaccine candidates have failed so far to date. Nobel laureate winner Dr. David Baltimore has even gone on to say that there has been no real incremental progress in HIV and AIDS vaccine discovery within the last 20 years.

Nevertheless, there are still high hopes for genuine cures that prevent the transmission of HIV and AIDS. Earlier this year, the director of the CDC himself, Dr. Robert Redfield, has said that the science to eradicate the HIV epidemic exists today. So without further ado, here are some promising candidates currently in the pipeline.

Possible Cures for HIV in Development

A Double Whammy Cure for HIV

Click to go to company websiteGilead Sciences (GILD) is a listed pharmaceutical research company that boasts $26 billion annual revenues and focuses on early discovery and development of primarily antiviral treatments for HIV, hepatitis and influenza. In a research partnership with the Beth Israel Deaconess Medical Center supported by the Bill & Melinda Gates Foundation, Gilead revealed a new experimental anti-retroviral drug earlier this year.

By combining their proprietary small-molecule drug, GS-9620, which works by forcing HIV out of its dormant state inside immune cells, with a PGT121 human antibody that has been shown to bind and neutralize 65 to 70 percent of HIV-1 at low concentrations, the new combo drug has shown promising results in preclinical animal trials conducted with rhesus monkeys. Out of 11 Simian/Human Immunodeficiency Virus (SHIV)-infected monkeys, five had low-level viral loads, while the remaining monkeys could suppress the virus without ongoing antiretroviral therapy. The promising results are part of a new track of “double whammy” drug strategies to eradicate HIV.

Genetic-based Cures for HIV

Click to go to company websiteSangamo Therapeutics (SGMO) is another publicly traded pharmaceutical company headquartered out of California, which focuses on that research around gene-based therapeutic drugs. Sangamo is conducting the first ever in vivo human genome editing studies to modify human T-cells into expressing a mutant form that HIV can’t enter, rendering the immune cells permanently resistant to infection by the virus. The company is currently in a Phase 2 clinical study to evaluate the safety and efficacy of the drug, SB-728-T, as a potential first cure to HIV.

A graphic that only a scientist could love.

A graphic that only a scientist could love. Credit: Sangamo

In 2016, Sangamo reported in a partial release of study results that four out of nine patients treated with the gene therapy remained off antiretroviral therapy. Stay tuned for the remaining results forthcoming this year.

Click to go to company websiteFounded in 2013, Abivax (ABVX:FP) is a French clinical-stage biotechnology company headquartered in Paris that raised about $23 million before going public more than three years ago. ABX464 is their lead candidate, and is currently undergoing Phase 2 clinical trials. As an oral anti-viral molecule, ABX464 works by targeting the hybrid protein-RNA replication machinery of HIV from within the infected cell’s nucleus.

ABX464 works by targeting the hybrid protein-RNA replication machinery of HIV from within the infected cell’s nucleus.

ABX464 works by targeting the hybrid protein-RNA replication machinery of HIV from within the infected cell’s nucleus. Credit: Abivax

This mode of action prevents HIV from undergoing the process of recreating more viruses, which would normally cause the infected immune cells to die. Recent data released within the past three months were encouraging, showing the drug could clear patients of HIV over 28 days, but didn’t delay viral rebound.

Immunotherapy Cures for HIV

Click to go to company websiteFounded in 2000 through a merger, Bionor Immuno AS is privately held Norwegian biopharmaceutical company that has taken in an undisclosed amount of funding to focus on developing immunotherapy treatments for HIV. Vacc-4x and Vacc-C5 are two proprietary vaccines that the company has developed and completed clinical trials on. Bionor’s platform technology is based around selecting the most vulnerable proteins attached to HIV and stimulating the immune system with both these proteins and an immune response-enhancing adjuvant. In the same way as any other vaccine, the body learns to respond quickly to these proteins, so when an HIV finds its way in, the body can focus on recognizing those vulnerable parts of the virus.

Click to go to company websiteFounded in 2008, Immunocore is a privately held British biotech company based in Oxfordshire that has raised $360 million, including $40 million last year from the Bill and Melinda Gates Foundation. Their drug technology, ImmTAC, is based on harnessing the immune system to recognize and kill off latent HIV hiding inside immune cells using engineered T-cell receptors that bind directly to HIV particles. Currently in pre-clinical trial stage, the technology has been shown to work in human tissue samples.

Immunocore's technology, ImmTAC, is based on harnessing the immune system to recognize and kill off latent HIV hiding inside immune cells using engineered T-cell receptors.

Immunocore’s technology, ImmTAC, is based on harnessing the immune system to recognize and kill off latent HIV hiding inside immune cells using engineered T-cell receptors. Credit: Immunocore

Conclusions

The hope for a successful HIV vaccine candidate remains strong despite the setbacks of the past two decades. While researchers continue to scramble for a drug that can actually prevent the AIDS epidemic from spreading, organizations like the Bill & Melinda Gates Foundation will keep pumping grant money into the research machine. With the potential explosion in biotechnology that’ll be made available by human gene-editing research through CRISPR, the future is still bright for the discovery of an HIV cure. And that will be nearly 37 million people who won’t have to live with this life-threatening disease.

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