Jessica Conway has spent her career studying patterns. Initially, she probed the patterns that form in vibrated fluid layers. But she quickly turned her attention and modeling skills to epidemiology and understanding the patterns seen in disease data, such as how the timing of vaccination influences the severity of a flu season. Conway and her group have now developed a model that predicts if and when the HIV virus will rebound if someone stops taking their medication. Speaking in early January at the Dynamic Days conference in Hartford, Connecticut, she said the model could help inform efforts to find a so-called functional cure, where the disease is kept below detectable levels without the need for continued drug intervention.

“Our aims are modest,” Conway says. “We don’t want to go to a clinician and say, ‘do this.’ Rather we want to generate hypotheses and make testable predictions as to what mechanisms might delay or control viral rebound.”

HIV is a disease of the immune system. The disease infects white blood cells, known as CD4 cells, and then uses the machinery of these cells to replicate and spread through the body. Antiretroviral therapies disrupt this cycle by stopping the virus from replicating. But the drugs are not a cure. Typically, when a person living with HIV stops taking their medication, the virus starts to replicate again, and the amount of HIV in the blood (the viral load) jumps back up. There is significant variability in the timing of this rebound, which can take from days to years. In fact, two studies, one in France and the other in the US, identified some HIV sufferers whose viral load never rebounded. Conway wanted to see if she could explain the variability in rebound times.

Conway’s model predicts an individual’s viral state at future times, given certain initial medical indicators. Her approach is based on a standard model of viral dynamics, which captures the infection and spreading of the virus via CD4 cells through a series of coupled differential equations. But Conway’s version has two important modifications. First, she added in the effects of so-called latently infected cells. These are infected cells that may lie dormant for days, months, or years and then suddenly wake up and start spreading the disease. If a person with HIV stops taking their drugs, these latently infected cells can cause the infection to rebound. She also included the impact of “killing” cells, which destroy infected cells and are meant to mimic the natural immune response. She then ran the model, varying parameters such as the efficacy of the killing cells and the number, or “reservoir size,” of latent cells in the body.

In 2015, Conway succeeded in predicting three medically observed outcomes from a single rebound model. She found that rebound occurs below a certain killing rate, while rebound is avoided when killing rates are high enough and latent reservoirs are sufficiently small. Finally, a certain combination of inputs led to a third state called elite control, where an infected individual keeps the disease at bay without ever needing medication.

More recently, Conway has also captured the variability in observed viral rebound times using a simplified version of the model, which predicts the distribution of rebound times for a group. The essential assumption is that the activation rate of the latent cells—when they wake up and start producing virus—decays exponentially in time. “An exponentially decaying rate does a great job at capturing the short and long delays,” Conway says. “It captures them a lot better than we anticipated.” But Conway notes that this behavior is still under investigation and the results have yet to be vetted by peer review.

Now that Conway has a model that can replicate a diversity of HIV rebound scenarios, she hopes the information could be used by doctors to better plan clinical trials that work toward a functional cure for HIV. For example, her model predicts that if rebound occurs, it should happen within 1 to 4 weeks for 90% of people with HIV. That information could help determine how soon a person should get tested after stopping therapy. The model could also be used to inform treatment strategies that aim to avoid rebound. For example, knowing that a small latent reservoir is key to stopping the virus from rebounding, clinicians might monitor biomarkers associated with an individual’s reservoir to determine how, when, or if the person should be taken off their drugs.

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A new report has shown a high level of novelty and diversity for the HIV first-in-class pipeline which targets drug resistance and latency reversal.

According to a new report, the HIV pipeline is robust, with 450 products in active development that display a high degree of novelty and diversity. Promisingly, there are 87 first-in-class products that act on a range of 50 molecular targets, which can broadly be classified as host or viral factors, indicating a high level of innovation in comparison with the marketed products.

The report by GlobalDatacontinued that the majority of the 10 highest-ranking targets have demonstrated evidence, either in vitro or in vivo, of latency-reversing potential and/or efficacy in drug-resistant HIV strains which shows that first-in-class innovation is centred on addressing these major unmet needs in the HIV market.

“The persistence of latent HIV reservoirs in antiretroviral therapy (ART)-treated patients represents a major barrier to the development of a functional cure, while the global rise in HIV drug resistance compromises the significant advances in disease management that have been achieved since the 1980s,” said Sarah Elsayed, Pharma Analyst at GlobalData. “However, the most pressing unmet need remains to be a cure that results in viral eradication.”

Furthermore, HIV vaccines have a strong presence in the overall pipeline (27.2 percent), the report states. Preventive and curative vaccines have received high attention in research recently, since they may potentially translate into a cure that will eradicate the virus and help control the HIV pandemic, the report pointed out. 

Cell/gene-based therapy is also being investigated in the early stages of development, with two first-in-class products, both of which are at the discovery stage, the outlet said, which is different from the conventional antiretroviral treatment, since it can potentially be translated into a revolutionary cure in the near future.

“Although 60 percent of these pipeline drugs are still in early development, the innovation of molecular targets is promising and presents the potential to expand the existing HIV drug classes, which have not completely fulfilled the primary unmet need for long-acting therapies,” Elsayed concluded.

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TALLAHASSEE, Fla.(WTXL) — A new discovery by Florida State University College of Medicine researchers is expected to help in the fight against the HIV virus and hepatitis B.

According to Florida State University, the study will open the door for new and more potent treatment options for many of the more than 36 million people worldwide impacted by HIV and hepatitis B.

The work of researchers has established for the first time the mechanism responsible for how two widely used antiviral drugs inhibit viruses.

In a paper published by Communications Biology , an open-access journal from Nature Research, Professor Zucai Suo and colleagues provide the key to understanding how a single HIV-1 mutation can inactivate the anti-HIV drugs.

FSU says those drugs are worth billions in annual sales for the companies that make them.

The paper discusses new pathways for developing drugs able to avoid specific virus mutations that can render these drug treatments ineffective for many patients.

Officials say the number of drug choices available when one combination fails is limited. More than a million of those infected with HIV live in the U.S.

“In our paper, we suggest new chemical possibilities for more potent L-nucleoside analog drugs, which may possess different drug-resistance mutation profiles from the most widely used current anti-HIV drugs,” said Suo, the study’s co-lead author, and an Eminent Professor and the Dorian and John Blackmon Chair in Biomedical Science at the FSU College of Medicine. Eric Lansdon of Gilead Sciences Inc. is the co-lead author.

“Right now, there are a limited number of FDA-approved drugs available,” Suo said. “New drugs need to be developed if doctors are to have other options when treating so many patients who may have developed resistance to most of the FDA-approved anti-HIV drugs.”

Researchers say the drugs remain highly effective in keeping the disease under control for most patients, however some patients manage to develop a resistance due to mutations within the HIV virus.

Suo’s current paper also explains how a mutation found in some patient populations leads to developing resistance to antiviral L-NRTI drugs.

The university says this work was supported by Gilead Sciences Inc. and a grant from the National Science Foundation.

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Last week, the FDA denied the approval of Cabenuva, the first of its kind monthly HIV injection treatment. Developers hoped that the monthly injection would replace daily pills, thus making life easier for HIV patients and also possibly removing some of the stigma associated with the disease. 

According to ABC News, the FDA had no concerns with the drug’s efficacy or safety. Rather the application’s denial was due to concerns regarding the drug’s manufacturing process. In their Complete Response Letter (CRL) regarding the New Drug Application, the FDA stated their rejection was related to “Chemistry, Manufacturing, and Controls (CMC),” EMPR reported.

Cabenuva passed trials and proved to be effective at repressing virus levels in HIV-positive patients. New trials will not be required as the FDA denial was not related to concerns with drug safety. Instead, the manufacturers plan to “work closely and with urgency with the FDA to determine the appropriate next steps for this new drug application,” a drug spokesperson told ABC News. 

“Clearly this is disappointing and not the news we hoped for,” said a spokesperson.

HIV is a virus that weakens a person’s immune system by interfering with their ability to fight off infection. Although there is no cure, there are certain medications that can help control the disease by slowing the virus’ progression in the body. These drugs may also aid in lowering an individual’s risk of spreading HIV to others by reducing the amount of the virus in your body, the Center for Disease Control and Prevention report. 

The Cabenuva injection contains two active ingredients (cabotegravir and Janssen’s rilpivirine). The long-lasting drug is administered every four weeks. For some HIV patients there is a fear of stigma associated with their health status. Release from the dependence of daily pills may save some from this stigma. 

In addition to HIV treatment, there are also medications used called PrEP (Pre-Exposure Prophylaxis), which help prevent HIV negative individuals from contracting the virus. The combination of these HIV prevention and treatment medications have helped to slow the rate of HIV transmission in the U.S. and improve the lives of those living with the virus.

Although the FDA cited that there were no concerns with the safety of Cabenuva, doctors express concerns of may come along with a monthly injection versus a daily pill. For example, patients who miss an injection may be at greater risk for the virus to grow in numbers and strength, ABC News reported. 

The drug application was filed by ViiC Healthcare, which is majority-owned by GlaxoSmithKine. Pfizer and Shionogi also have small stakes.

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Scientists at US healthcare major Abbott Laboratories have discovered a new strain of HIV virus, the company has announced.

The new subtype of the human immunodeficiency virus is called HIV-1 Group M, subtype L, the group that led to a global pandemic. A new strain of the HIV virus has been found after 19 years.

“This research marks the first time a new subtype of ‘Group M’ HIV virus has been identified since guidelines for classifying new strains of HIV were established in 2000. Group M viruses are responsible for the global pandemic, which can be traced back to the Democratic Republic of Congo (DRC) in Sub-Saharan Africa,” said Abbott in a statement.

The findings, published in the Journal of Acquired Immune Deficiency Syndrome (JAIDS), show the role next-generation genome sequencing is playing in helping researchers stay a step ahead of mutating viruses and avoiding pandemics.

Since the beginning of the global AIDS pandemic, 75 million people have been infected with HIV and 37.9 million people today are living with the virus.

Even though the new HIV infections are going down globally, researchers are monitoring new strains to make sure testing and treatments continue to work.

There is no cure for AIDS, the disease caused by the HIV virus, but the viral load is controlled through Antiretroviral (ART) therapy.

Abbott created its Global Viral Surveillance Program 25 years ago to monitor HIV and hepatitis viruses and identify mutations to ensure improved testing mechanisms.

“Identifying new viruses such as this one is like searching for a needle in a haystack,” said Mary Rodgers, principal scientist and head of the Global Viral Surveillance Program, Diagnostics at Abbott, and one of the study authors, in a statement.

“By advancing our techniques and using next generation sequencing technology, we are pulling the needle out with a magnet. This discovery can help us ensure we are stopping new pandemics in their tracks,” she added.

The company is making the new strain accessible to the research community to evaluate its impact to diagnostic testing, treatments and potential vaccines.

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