{"id":2309,"date":"2018-10-12T04:12:57","date_gmt":"2018-10-12T04:12:57","guid":{"rendered":"https:\/\/www.mybiosource.com\/learn\/?p=2309"},"modified":"2023-03-06T13:15:56","modified_gmt":"2023-03-06T13:15:56","slug":"std-series-is-functional-cure-on-the-horizon","status":"publish","type":"post","link":"https:\/\/www.mybiosource.com\/learn\/std-series-is-functional-cure-on-the-horizon\/","title":{"rendered":"STD Series: Is Functional Cure on the Horizon?"},"content":{"rendered":"

Table of Contents<\/strong><\/span><\/h2>\n

I. Introduction<\/strong>
\n\u2022 The need for a functional cure for HIV
\n\u2022 Antiretroviral therapy (ART) and its impact on HIV treatment
\n\u2022 Definition of a functional cure
\nII. Strategies for HIV cure research<\/strong>
\n\u2022 Gene therapy
\n\u2022 Immunotherapy
\n\u2022 Shock and kill approach
\nIII. Conclusion<\/strong>
\nA. The importance of continued HIV cure research<\/p>\n

\n

Ever since Timothy Ray Brown<\/a><\/strong> escaped the clutches of HIV<\/span>, the idea of a functional cure for HIV<\/span> continues to be a distant dream for researchers and the medical community. Nearly 37 million people in the world are living with HIV<\/span> today, and sadly over 1.8 million new cases are piling up every year, despite colossal spending and monumental efforts put in by different governments and health regulators to firefight the spreading of HIV<\/span>.<\/p>\n

Since the mid-80s, Antiretroviral therapy<\/span> (ART<\/span>) has been used to prolong the lives of HIV<\/span> infected people. The Food and Drug Administration<\/span> over the last 30 years had certified six more classes of drugs \u2013 all focused on blocking viral replication<\/span> within the human body.\u00a0 In total, under seven classes, nearly 40 drugs are marketed under different brand names. Also, the screening landscape has changed drastically to accommodate the need of the hour, and the tests have become more sensitive and specific to HIV<\/span>.<\/p>\n

As a result, the deaths due to HIV<\/span>\/AIDS significantly dropped, and the AIDS epidemic was arrested. In 2012, The regulators approved PrEP<\/a><\/strong> for use among the high-risk population, another preventive measure in addition to using condoms.<\/p>\n

With an increase in the number of HIV<\/span> patients year over year, the need for a functional cure is more of a necessity than comfort, as people infected with HIV<\/span> undergo an enormous amount of trauma and stigma throughout their remaining life term. Besides, even though the life expectancy of affected individuals were restored to near normal by Antiretroviral therapies, the side effects due to treatment or HIV<\/span> is too burdensome to bear for anyone, and some of the side effects<\/a> are accelerated aging, cognitive<\/span> impairment, inflammation-related complications, effects on lipid levels and cancer.<\/p>\n

What is a functional cure? <\/strong><\/p>\n

In a broader sense, treatments that are focused on eradicating the virus in the bloodstream and reservoir cells could be considered as a functional cure. Interestingly, this would leave the infected individual with a healthy immune system – free of the virus and free from medications. As melodramatic as it seems, some institutions and organizations are working towards this finish line called the functional cure.<\/p>\n

At present, if a patient stops taking antiretroviral therapy<\/span>, the virus would continue to multiply and spread via the bloodstream or would kick in from reservoir cells. Eventually, the patient must return to antiretroviral treatment to protect the immune system. According to a study presented at the 6th International Conference on HIV Treatment and Prevention Adherence<\/a><\/em>, an interruption of just two days is significant enough for the viral load<\/span> to increase in patients. Also, the patients with HIV<\/span>, if interrupted with the treatment, would risk of having a detectable viral load<\/span> in a fortnight.<\/p>\n

What\u2019s cooking? <\/strong><\/p>\n

Research institutions across the world use different approaches\/strategies to solve the HIV<\/span> puzzle. Four well-known strategies under the radar are Gene therapy, Immunotherapy<\/span>, Shock and kill approach and stopping the replication of HIV<\/span>.<\/p>\n

Gene therapy <\/strong><\/p>\n

It is widely believed 1% of the world population inherit CCR5 delta-32, and of which majority inherit homozygous CCR5 gene copies resulting in the expression<\/span> of a shortened, non-functional CCR5 protein. This mutation seems to have no adverse health impacts but confers immunity<\/span> to the individuals.<\/p>\n

Based on this underlying science, Sangamo Therapeutics have two exciting candidates in the pipeline \u2013 one in phase 1 and another in phase 2.\u00a0 As crazy as it sounds, the company is planning to artificially edit CCR5 gene (propriety ZFN-mediated genome editing technology) in patients\u2019 immune cells<\/span> and reintroduce it in the body.<\/p>\n

These cells would be permanently resistant to HIV<\/span> and therefore fight off both HIV<\/span> and opportunistic infections<\/span>. This approach almost mimics how Mr. Timothy Ray Brown<\/span> got rid of HIV<\/span>.<\/p>\n

On February 07, 2018, the company and Western Reserve University jointly announced that they received a grant of $11 million from the National Institutes of Health for a planned study (involving 20 patients) of gene-edited T cells designed to eradicate\u00a0persistent HIV<\/span> infection in patients receiving antiretroviral therapy<\/span>, a combination of medicines that slow the rate at which HIV<\/span> replicates.\u00a0Until now, there were no adverse events reported related to this study.<\/a><\/p>\n

Immunotherapy<\/span><\/strong><\/p>\n

One of the most promising of all buzz going on around HIV<\/span> drug research is the recently published study by IrsiCaixa AIDS Research Institute and the Fight AIDS Foundation. In a clinical trial<\/span> of 13 participants, five are reported to be off antiretrovirals from 5 weeks to 27 weeks, at the time the study was made public. i.e., February of 2017. The clinical trial<\/span> has proved that it is possible to re-educate the immune system to take control of the body, thereby weakening the hold of HIV<\/span> over immune cells<\/span>.<\/p>\n

The same team sitting in Europe (Spain and UK) is also focused on developing a vaccine that can mount an immune response thousand times stronger than usual to kick out (kick and kill strategy) the virus when induced to come out from reservoir cells.\u00a0 In 2016, the same team reported 5 of 15 patients were clear of HIV<\/span> for seven months.\u00a0 The team is also trying to understand why almost half the participants in the study were not responding to their experimental therapy. To know more about this study.<\/a><\/p>\n

Kick and Kill Approach<\/strong><\/p>\n

Once thought to be an exciting strategy, (to wake up reservoir cells and then kill them using vaccine or immune boost), the disappointing results from the River Study<\/a> published in August of this year has brought a negative connotation to this approach. Interestingly, this is one of the studies that many were looking forward to as it involved nearly 60 participants. The test results indicated there was no difference in the measure of the viral reservoir between people who were only taking ART<\/span> and people who received the \u201ckick and kill\u201d strategy.<\/p>\n

Not to be upset with the River Study results, there is one more ongoing study based on this approach. Oslo-based Biopharma Bionor published its phase 1 results in July of 2016; the vaccine infusion reduced viral presence in 88% of patients to an undetectable level after combination treatments with Celgene\u2018s enzyme inhibitor, Istodax, and standard retroviral<\/span> drugs. To know more about this study.<\/a><\/p>\n

Killing the reservoirs and replication process<\/strong><\/p>\n

The most straightforward approach of all, inhibiting the replication process of HIV<\/span> is not as easy as it sounds. The French drug manufacturer Abivax drug candidate ABX464, (focused on killing viral reservoirs) in combination with Antiretrovirals, showed a 25% to 50% reduction in HIV<\/span> reservoirs in Phase 2a results, which is a significant milestone in the search for the functional cure. The new data published by the company in July 2018 showed mixed results but is encouraging for the right reasons.\u00a0 \u00a0To know more about this study.<\/a><\/p>\n

Road Not Taken<\/strong><\/p>\n

A novel approach to solving the HIV<\/span> puzzle is also on the horizon; researchers at Kumamoto University believe in locking and killing the virus by injecting this newly developed compound (L-HIPPO) and triggering infected cell death through apoptosis<\/span>.<\/p>\n

Road Ahead<\/strong><\/p>\n

It is very heartening to see several leading pharmaceutical firms pursuing eradication strategy by backing academic studies focused on functional cure rather than to rely on Antiretrovirals to mint money.\u00a0 In early 2018, Gilead Sciences<\/a> reported encouraging data from an animal study indicating that a two-drug regimen was able to suppress HIV<\/span> for several months even after treatment was discontinued.<\/p>\n","protected":false},"excerpt":{"rendered":"

Table of Contents I. Introduction \u2022 The need for a functional cure for HIV \u2022 Antiretroviral therapy (ART) and its impact on HIV treatment \u2022 Definition of a functional cure II. Strategies for HIV cure research \u2022 Gene therapy \u2022 Immunotherapy \u2022 Shock and kill approach III. Conclusion A. The importance of continued HIV cure […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"off","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[31],"tags":[33,13],"class_list":["post-2309","post","type-post","status-publish","format-standard","hentry","category-news","tag-functional-cure","tag-hiv"],"_links":{"self":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts\/2309","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/comments?post=2309"}],"version-history":[{"count":0,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts\/2309\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/media?parent=2309"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/categories?post=2309"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/tags?post=2309"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}