HIV Virus in the bloodstream / Photo by Shutterstock
Scientists were stunned after almost a decade of ongoing research and clinical trials involving the hunt for the possible cure for HIV. Such developments have long been established from antiretrovirals to therapies involving the use of genes and other substances. New discoveries by scientists aid progression towards leading a step closer in finding a remedy to this disease.
Since its first discovery in the 1980s, efforts to find the cure had been unsuccessful and yet these experiments had provided subsequent information vital for the researches that are being conducted today. Various data involving the disease and potential treatments have come a long way since then.
Updates on Clinical Researches
Researches at Temple University and the University of Pittsburgh unveiled a proof-of-concept study that described how the CRISPR-Cas9 gene-editing tool could be used to eliminate HIV from infected cells. Now, in another potential step towards a permanent cure, the team has demonstrated that the technique works to keep the virus from spreading and, in latent cases, rips it from its hideout. The animal trial was conducted into three phases of HIV infected mice and was successful in inactivating the virus.
Once the virus is out from hiding, it makes it easier locating and removing the virus. Mice with an acute infection of the equivalent virus (called EcoHIV) were the primary source of the study involving the gene tool.
"During acute infection, HIV actively replicates," says Dr. Kamel Khalili, co-lead author of the study. "With EcoHIV mice, we were able to investigate the ability of the CRISPR-Cas9 strategy to block viral replication and potentially prevent systemic infection."
"The next stage would be to repeat the study in primates, a more suitable animal model where HIV infection induces disease, in order to further demonstrate elimination of HIV-1 DNA in latently infected T cells and other sanctuary sites for HIV-1, including brain cells," says Khalili. "Our eventual goal is a clinical trial in human patients." he added.
As stated in Science Daily, researchers from UNSW Sydney and the UK have discovered that the human immunodeficiency virus (HIV) hijacks a small molecule from the host cell to protect itself from being destroyed by the host's immune system. They were able to identify a new target for antiviral therapy against HIV and provide a method for testing and measuring new drugs designed to target the capsid.
UNSW Ph.D. student Chantal Márquez, conducted the study and was the first who pioneered the new method.
HIV forms a protein shell -- called a capsid -- that shields its genetic material from host defense mechanisms as it enters the cell and makes its way to the nucleus to establish infection.
The research teams found that HIV specifically incorporates a small molecule -- inositol hexakisphosphate -- to strengthen its capsid. The researchers also found that inositol hexakisphosphate, which is abundantly present inside mammalian cells, makes the capsid much stronger, stabilizing it for 10-20 hours.
"It's like a switch. When you bind this molecule, you stabilize the capsid, and release the molecule to open it up," explains Associate Professor Böcking.
"The HIV capsid has been intensively studied, but it remains as one of the great mysteries in HIV biology," says Dr. Leo James, leader of the research team at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK.
Most of the currently approved HIV therapies target enzymes needed at different stages of the virus' life cycle, but none of them are actually directed at the HIV capsid. New drug alternatives could improve the treatment of HIV with reduced toxic effects.
The Berlin Patient
A patient named Timothy Brown was the very first HIV patient to be rendered cured of the disease after almost a decade without antiretrovirals. The virus was undetectable in his system and thus was considered ‘free’ from the disease. Prior to the prognosis of the disease, he had received a bone marrow transplant from a healthy HIV non-reactive donor. With this glorious feat, the world of medicine subjected to further research to finally search for the potential cure for this unlikely affliction.
However, attempts to replicate the Berlin patient case have not been successful and the procedure of bone marrow transplants carry high risks for HIV-positive patients. There have been improvements on antiretroviral drugs and HIV vaccines are underway, but an HIV cure has remained elusive.
One of the biggest concerns around any HIV treatments is the virus’ ability to quickly mutate and develop resistance, and for many of these new approaches, there is still no data on whether the virus will be able to become resistant.
Further research shows that a cure is soon underway in the year 2020, we hope that this will now be the key in finally being able to provide this disease to an end. Some are skeptical since no method had been passed for late-stage clinical testing yet, thus it might not seem we have found a cure so far. However, this would be the start of a milestone which would advance the continuous search for a prospective medical treatment. Most likely, if rendered successful, then the approval of the first functional HIV cure will finally be made available.
In the 35 years of the HIV epidemic, only four HIV vaccine concepts have been tested in humans, and only one has provided evidence of protection in an efficacy trial -- a canarypox vector prime, gp120 boost vaccine regimen tested in the RV144 trial in Thailand lowered the rate of human infection by 31% but its effect was considered too low to advance the vaccine to common use.
However, simultaneous vaccine trials were conducted and finally clinched the impending efficacy of the immunity regimen at a larger scale.
A team of researchers had passed this struggle to ever been the closest to producing a successful vaccine, with an experimental drug moving to a large-scale human trial in southern Africa.
As published from The Lancet, Dan Barouch from Harvard Medical School, and one of the researchers leading to the prior successful vaccine trials does urge caution, suggesting that the challenges faced in developing an effective HIV vaccine are unprecedented and excitement should be moderated.
"We eagerly await the results of the phase 2b efficacy trial called HVTN705, or 'Imbokodo', which will determine whether or not this vaccine will protect humans against acquiring HIV," says Barouch.
According to research, an experimental HIV-1 vaccine regimen is generated comparable and had robust immune responses against HIV in healthy adults and rhesus monkeys. Moreover, the vaccine candidate was protected against infection with an HIV-like virus in monkeys.
In a parallel study, the researchers assessed the immunogenicity and protective efficacy of the same Ad26-based mosaic vaccine regimens in rhesus monkeys using a series of strains from simian-human immunodeficiency virus (SHIV) -- a virus similar to HIV that infects monkeys.
The Ad26/Ad26 plus gp140 vaccine candidate induced the greatest immune responses in humans and also provided the best protection in monkeys. They also note that there is no definitive immunological measurement that is known to predict protection against HIV-1 in humans.
New vaccine concepts and vectors are in development and can progress to efficacy trials, which is an important process since the development of an AIDS vaccine remains urgent. Despite unprecedented advances in HIV treatment and prophylaxis, the number of people living with HIV infection continues to increase worldwide. Implementation of an effective HIV vaccine together with the existing HIV prevention and treatment strategies is expected to contribute greatly to the evolving HIV/AIDS response. It is therefore essential that a commitment to pursue multiple vaccine development strategies continues at all stages.
Previous HIV-1 vaccine candidates have typically been limited to specific regions of the world. The experimental regimens tested in this study are based on 'mosaic' vaccines that take pieces of different HIV viruses and combine them to elicit immune responses against a wide variety of HIV strains.
"These results represent an important milestone. This study demonstrates that the mosaic Ad26 prime, Ad26 plus gp140 boost HIV vaccine candidate induced robust immune responses in humans and monkeys with comparable magnitude, kinetics, phenotype, and durability and also provided 67% protection against viral challenge in monkeys," says Professor Dan Barouch, Director of the Center for Virology and Vaccine Research.
He adds: "These results should be interpreted cautiously. The challenges in the development of an HIV vaccine are unprecedented, and the ability to induce HIV-specific immune responses does not necessarily indicate that a vaccine will protect humans from HIV infection. We eagerly await the results of the phase 2b efficacy trial called HVTN705, or 'Imbokodo', which will determine whether or not this vaccine will protect humans against acquiring HIV."
A hurdle to most HIV vaccine development has always been the lack of direct comparability between clinical trials and preclinical studies. To address these issues, Barouch and colleagues evaluated the leading mosaic adenovirus serotype 26 (Ad26)-based HIV-1 vaccine candidates in parallel clinical and pre-clinical studies to identify the optimal HIV vaccine regimen to advance into clinical efficacy trials.
This is one of only five experimental HIV-1 vaccine concepts that have progressed to efficacy trials in humans in the 35 years of the global HIV/AIDS epidemic. The vaccines administered were proclaimed safe and thus paved the way to further clinical trials to be conducted soon.
It is estimated that 1.8 million people contract HIV every year.
CRISPR-Cas9 gene editing tool / Photo by Shutterstock