Posts tagged Antiretroviral drugs
Drugs are often a double-edged sword. While their purpose is to cure or alleviate symptoms caused, many of them come with complications. This is often the case with drugs for severe conditions such as HIV drugs.
Furthermore, HIV is one of the most troublesome diseases in the world. Medications help fight off the virus but they can also have adverse effects on the body. One of the most common drugs for HIV is abacavir. The side effects of this drug are rare but a certain portion (5 to 8 percent) of patients do experience an intense allergic reaction to it.
Abacavir is known to cause hypersensitivity syndrome. This is a life threating reaction which can cause fever, rash, nausea, vomiting, diarrhea, and abdominal pain. If patients have a particular human leukocyte antigen (HLA), these symptoms usually appear within the first two to six weeks of taking the HIV drug.
The HLA protein is a substance that induces an immune response. These proteins are located on the surface of a cell and often communicate with T-cells. If an entity other than a co-binding peptide binds to an HLA protein and changes it, the protein will deem it foreign. This signals the T-cells, and cause an immune response. Often, the abacavir drug appears as an unknown entity when it tries to bind to the cells.
Researchers Take a Closer Look at HIV Drug
A test was performed at North Carolina State University. Researchers used a computer model to get a closer look at the abacavir drug reaction on a molecular level. They wanted to see the drug’s interaction with the HLA proteins.
“There are 15,000 variants of HLA, and everyone carries some of these variants,” says Denis Fourches, assistant professor of chemistry at NC State. “HLA-B*57:01 is one of the first variants studied in the context of a drug-induced immune reaction. We know that it binds with abacavir, but little was understood about exactly what was happening structurally at the molecular level, especially in terms of the relationship with the co-binding peptide. This is a very complex system.”
The computer was able to create 3D models of the HLA protein, abacavir, and the co-binding peptides. Researchers simulated the docking process with and without co-binding peptides. They also ran simulations of the process with 13 other HIV drugs that have similar effects.
“The models allowed us to identify key atomic interactions that cause abacavir and other drugs to bind to the HLA variant protein and ultimately trigger the immune response,” Fourches says. “When you can forecast and understand the elements of the drug that enable the binding to occur, you may be able to create new active compounds that do not have that problem.”
The research team at NC state hopes that his in-depth look at binding process will provide them a better understanding of how the immune system reacts to drugs. With this knowledge, they can predict the side effects of medications. In the future, they can also build better drugs. Hopefully, they will avoid life-threatening situations.
The advancements in HIV treatment have made it easier to stall the progression of the virus. However, a new study suggests that the news of these treatments is having an unintended consequence. More gay men are engaging in risky behavior because they believe that antiretroviral medicines will keep them safe. However, the continuation this kind of behavior only increases their risk despite taking proper prevention methods.
The Risk to Gay Men
Gay Men are already more likely to contract HIV than others. In 2015, gay and bisexual men accounted for 67 percent of all new diagnoses. Anal sex is the highest risk factor for HIV transmission. Receptive anal sex puts more men at risk than insertive anal sex. This is because of the rectums thin lining, which allows HIV to enter the body more easily. The transmission of HIV can happen from semen or pre-seminal fluid.
The Danger of Relying Solely on Medicinal HIV Treatment
Study leader Seth Kalichman of the University of Connecticut and his team analyzed a survey spanning 19 years. Participants at a gay pride event noted their sexual habits. Here is what they found:
- An increase in condomless sex among men.
- A rise in the number of sexual partners that men engaged with.
- Condomless receptive anal sex has doubled in HIV-negative men.
- Condomless insertive anal sex has tripled in HIV-negative men.
We are seeing a considerable increase in unsafe sex because gay men perceive antiretroviral drugs to be enough. However, after looking at the survey data, they found there wasn’t much of a reduction of new HIV infections in major cities. In fact, certain countries with HIV testing programs and antiretroviral drugs have seen infection grow among gay men. The risk remains when unsafe behavior increases.
Kalichman concludes that “The current study adds to the mounting evidence that substantial changes have occurred in community-held beliefs that condomless anal sex is safer in the era of HIV treatment as prevention.”
In the fight against HIV, antiretroviral drugs are the strongest weapon we have. While these medications do not cure or kill the virus, they stop it from progressing any further. Unfortunately, this treatment is a combination of several different types of drugs. When combined, they slow down HIV. However, according to new research, they may also leave significant neurological damage.
The Risks of Antiretroviral Drugs
Like most drugs for serious conditions, antiretroviral drugs do have side effects. However, their ability to stop the progression of HIV to AIDS has outweighed any minor complications. To this day, they are so successful that patients with AIDS are a rarity.
Some patients have been known to experience appetite loss, lipodystrophy, diarrhea, fatigue, mood changes, nausea, and bone loss. Scientists are working to make these drugs stronger and safer for patients. With the right precautions, patients can even make the side effects less debilitating.
The Connection to Alzheimer’s Disease
At the University of Pennsylvania, research has implicated some antiretroviral drugs in the progress of Alzheimer’s disease. They suggest that protease inhibitors are the cause. Protease inhibitors are the drugs that work the best against HIV. Apparently, some of these drugs promote the growth of the peptide beta-amyloid, which damages neurons.
“Protease inhibitors are very effective antiviral therapies, but they do have inherent toxicities,” said Kelly Jordan-Sciutto, senior author on the study. “Our findings may cause us to rethink how we’re using these drugs and even consider developing an adjunctive therapy to reduce some of these negative effects.”
Through testing, they were able to identify that the drugs did indeed cause the reaction and damage to the neurons. However, they are working to inhibit the enzyme called BACE1, which leads to the production of the beta-amyloid.
“Targeting PERK and/or BACE1 could help contribute to a therapeutic approach to treat drug-associated cognitive disorders.” said Jordan-Sciutto.
Finding effective treatment for HIV is a long-standing battle. Scientists are fighting against the disease every day. The search for answers may lead to drastic measures. However, at what point do the risk outweigh the cure? That’s the question posed by researchers at the Johns Hopkins University of Medicine when it comes to the ‘shock and kill’ treatment.
What is the ‘Shock and Kill’ Treatment for HIV?
The shock-and-kill treatment reveals HIV hidden within the cells. This is the problem that many scientists run into – HIV hides. When it is dormant, the virus does not trigger the immune system to fight back. It’s also the reason that antiretroviral therapies are only capable of keeping the disease at bay.
The proposed shock-and-kill treatment essentially wakes HIV from its dormant state to make it vulnerable to the immune system and antiretroviral drugs. However, testing this method has led scientists to believe the supposed ‘cure’ could have disastrous results.
The treatment was tested on the simian immunodeficiency virus (SIV), a disease that is found in primates and is very much similar to HIV. One of the test subjects displayed encephalitis symptoms and brain inflammation. The symptoms only worsened and the primate had to be put down humanely.
This treatment spells trouble if the disease is hiding within the brain. Activation in this area only makes a patient’s condition worse, especially when scientists do not know where the disease is hiding to begin with. Researchers advise caution.
“The potential for the brain to harbor significant HIV reservoirs that could pose a danger if activated hasn’t received much attention in the HIV eradication field,” says Janice Clements, Ph.D., professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine. “Our study sounds a major cautionary note about the potential for unintended consequences of the shock-and-kill treatment strategy.”
Studies have shown how a patient’s life expectancy with HIV has gotten better over the past 20 years. A lot of progress has been made. Researchers have found breakthrough treatment methods. And treatment itself has gotten more readily available.
It’s now well known that HIV is no longer a death march. Patients are now able to live fuller lives compared to previous decades. But how much longer are they expected to live for? And what factors lead to such vast improvements? Let’s take a closer look at that right now.
Life Expectancy With HIV Over The Years
From 1996-97, the death rate for HIV-positive people was at 7%. For people diagnosed with HIV, their average life span was typically 10 years. For 20-year-olds with the virus, it was higher. On average, they lived until 39. These numbers are now significantly better.
By 2006, that number jumped to 24 years. More than double the average from a decade previous. And a 20-year-old with HIV lived until 56 on average. That number is now in the high 60s. That leaves a separation of about 13 years between an HIV-positive and HIV-negative 20-year-old.
That’s the smallest gap in life expectancy between the two parties to date. It goes to show how far we’ve come in two decades. But that there’s still work to be done.
How Life Expectancy Has Improved
Antiretroviral Therapy (ART) was not yet readily available in 1996. That’s changed over the past two decades. As a result of there being easier access ART, it revolutionized HIV treatment. By preventing the virus from reproducing, ART is able to lower the viral load in the bloodstream. When successful, the viral load is so low that the virus is undetectable. HIV is still there. And it can still be spread to someone else. But there aren’t any symptoms.
Treatment is more effective across the board. Over half of those eligible for treatment are now receiving it. Also, Linkage to Care numbers continues to increase. The necessary work is being done.
In addition to being more effective, HIV treatment is now simpler, too. Fewer pills are needed. And there’s no longer a complex schedule to follow. A lot of patients can now take one pill a day and be fine. They work for a longer period of time and have fewer side-effects. It’s less likely for a patient to have to switch medications periodically.