HIV Management
Possible New HIV Therapies with the Discovery of Viral Insertion Variants
The human immunodeficiency virus (HIV) has the ability to attach its DNA to the host’s immune system’s DNA and manipulate the host cells to continue its replication process. This ultimately kills the affected cells, destroying the host’s immune system along the way. Researchers had long ago discovered that the HIV protein integrase is responsible for the HIV’s cell’s ability to attach itself to a host cell’s DNA, but for over twenty years they were not able to learn how this process actually happened. New discoveries into this process have shown that new HIV therapies are possible, because they are now attempting to retarget the entry points of the initial HIV cells, and thus weaken the virus’s ability to replicate so rapidly.
Researchers at KU Leuven’s Laboratory for Molecular Virology and Gene Therapy have learned that two amino acids are responsible for the integrase’s integration of the viral DNA to the host DNA. “HIV integrase is made up of a chain of more than 200 amino acids folded into a structure,” says Jonas Demeulemeester, one of the doctoral researchers working on this project. These amino acids, which are all folded in on each other, manipulate themselves in such a way that only two of the amino acids come into direct contact with the host’s DNA, and this becomes the initial entry point of the HIV cell.
The process of how HIV links to a host cell’s DNA is similar to related animal-borne viruses. Using this model to look at the animal-borne viruses, the researchers were able to learn that by manipulating and re-targeting the amino acids that make up the integrase they can cause the HIV cells to enter the host’s DNA at variant points. They learned that some entry points are more susceptible to a rapid replication and destruction of the host cells, and at the same time there are “safer” entry points of the host’s DNA which cause for a very slow and manageable reproduction rate of the viral cells. Now possible new HIV therapies exist because of this discovery, as we can now target the individual amino acids within the viral DNA, hopefully manipulating them into extinction.
In Africa, Traditional Healers Can Undermine Efforts of Modern HIV Treatments
Imagine you start to show signs of possible HIV infection: your skin color changes, your immune system is visibly weaker than ever before, and a flu-like feeling just won’t go away. You go to your trusted healer, the traditional healer your family has seen for years, decades, possibly generations. Now, imagine this traditional healer tells you that these symptoms are not due to a blood-borne virus infecting your body, but by a curse a neighbor has placed upon you and your family. His or her treatment will not recommend antiretroviral medications, but to chant incantations and rub medical herbs into an open cut made from a razor. Although this is not heard of as a practice in any area of the United States, no matter how rural, this type of traditional healing is still very common in rural areas of Mozambique and other sub-Saharan African countries. When these traditional healers speak of curses and angered ancestors as the causes for the HIV symptoms, there is an inevitable delay between the first signs of symptoms and the administration of the first antiretroviral medicines. Prolonging this crucial timeframe shows that these traditional healers can undermine efforts of modern HIV treatments, which can harm the patient in irreparable ways, possibly causing the individual to develop AIDS before receiving the medicine he or she needs.
A study led by Carolyn Audet, Ph.D., an assistant professor of Health Policy, focused on sub-Saharan African countries. Over 60% of the rural residents in this study who started showing symptoms of HIV infection visited at least one traditional healer before consulting a trained medical professional, sometimes seeing several healers before any doctors. This caused, on average, a two-and-a-half-time longer delay for receiving the needed medicine, as over 50% of those who saw traditional healers first were initially diagnosed with having a curse placed upon them. With countries like Mozambique having over ten percent of its population infected with HIV (in the US it is roughly 0.6%), mistreatment has become an epidemic of serious concern. These delays can undermine efforts of modern HIV treatments, as many traditional healers are resistant to incorporating Western medicine into their religious and healing practices, which can seriously harm or even cause the preventable death of patients before receiving life-saving antiretroviral medicines.
HIV May Evolve into an Ineffective Virus
HIV, like most viruses, evolves continually and at a rapid pace. Its process of replication is through constant mutation, so HIV cells can generate thousands of mutations of themselves. Some mutations die off before they take control over the virus cells of a host body, and some mutations become a dominant factor in the local virus population. Mutations that help the cells survive the longest have the best chance of dominating, and although some believe this may make HIV a stronger virus over time, there is evidence now emerging that shows the possibility that HIV may evolve – eventually – into a weaker, more treatable, and possibly ineffective virus.
The research showing this new evidence comes out of Africa. Philip Goulder, from the University of Oxford, and his team of researchers looked at the HIV epidemics in Botswana and South Africa. The epidemic started in Botswana roughly ten years before it hit South Africa, so the researchers took blood samples from roughly 2,000 HIV positive women from these two countries to compare the DNA structures of the viruses in each population. HIV cells in infected Botswanan women had developed mutations which helped them evade the immune system. Although this sounds like a bad sign, the mutations – in helping the virus evade detection – crippled the virus in many ways. Mutations in the Botswanan women slightly slowed down the replication speed of the virus cells, causing a 10% decrease in replication time. This slight variation helped the women’s immune systems keep up with the virus for a few years longer, causing a longer period between initial infection and when the virus caused AIDS to develop (meaning the immune system had been compromised completely).
This mutation only occurred over 10 years between when Botswana had its HIV outbreak and when the HIV outbreak spread to South Africa, so in a relatively short amount of time (one decade), HIV naturally evolved into a weaker virus. Goulder, of the research team looking at these mutations, says, “HIV can generate any mutation in the book, on any day,” so he’s not surprised that big mutations like this could occur so quickly. This mutation changes the time that the virus causes AIDS in untreated infected individuals to go from roughly 10 years to 12.5 years, which could mean the difference of life and death for those awaiting treatment. These mutations are already showing researchers where to focus their attacks on the virus, possibly leading to the development of an effective HIV vaccine. And, with the virus already mutating in this fashion, HIV may evolve to the point where the virus never completely compromises the natural human immune system, and where the immune system alone could maintain and control the HIV virus indefinitely.
How HIV Affects the Brain
HIV infection is known to cause several side effects as it invades the body. Because of advances in medicine, along with our overall understanding of what HIV is and how the virus works inside the human body, we have been able to prolong the side effects that was so disastrously prevalent in the 1980s and 1990s: death due to a completely compromised immune system. As we are now able to keep the virus essentially ineffective, even though we are still not able to eradicate it from the body, infected individuals are now able to live much longer than before, and many die of other natural causes before they develop AIDS from their HIV infection. With people now living longer than they were able to before, researchers have noticed slow-showing side effects that an elongated HIV infection can cause. One of the more feared, as well as least understood, side effects of HIV is its negative effects on a person’s mental abilities. To learn how HIV affects the brain, researchers out of Washington University in St. Louis have looked at one of the two leading theories on the subject.
The two leading theories on how HIV affects the brain are: 1) the early immune system’s responses to the infection which triggers a series of effects that slowly impair memory and mental function; 2) how the disease and co-infections commonly seen with HIV affect the brain independently of the HIV infection. The research team decided to focus on the co-infection theory, as they saw ways to judge whether these infections were indeed affecting the brain instead of HIV itself. Through statistical elimination, they determined the only co-infection which is common enough to affect so many HIV-infected individuals is hepatitis C. So, they looked at the effects of hepatitis C and the possibilities it has in affecting a brain when it is co-infected along with HIV. Knowing that this virus predominately attacks the liver led researcher David Clifford, MD, to rule out this theory, because he believes hepatitis C does not affect the brain in any directly negative manner. The study included almost 1,600 HIV infected individuals who roughly 400 were co-infected with hepatitis C. These patients were given two exams – one written and one physical – to determine any differences they may have in their cognitive and mental abilities. The exams looked at how the patients expressed themselves, made decisions, learned and retained new information, and controlled their body. The results were that there was no distinction between those co-infected with hepatitis C and those who were only infected with HIV. This lack of distinction was made even more impressive, according to Clifford, because those who were co-infected with hepatitis C were almost all older, had less of an education, and generally had lower reading and math scores than the others. They now feel the leading theory – that the immune system’s initial reactions of inflammation of the bowels and brain – is the correct one, and are working to prove this.
Are You More Immune to HIV Than You Thought?
For the past several decades, doctors and scientists could not understand why some people quickly get sick – and can die – when infected with HIV, while others seem to naturally resist the virus for several years with less damage done to their immune systems. Researchers at the University of Minnesota’s College of Biological Sciences and Medical School looked at the virus’s rapid-mutation ability, along with how it attacks the human immune system to replicate, and hypothesized that this distinct difference in how the virus differently affects infected individuals is somehow caused by the genetics of the infected host. In trying to understand why some are more immune to HIV than others, these researchers discovered a new crack in the HIV cell’s armor which helps explain this phenomenon.
HIV attacks the immune system in order to replicate within the infected host’s cells. It seeks out the immune system cells called T lymphocytes (T cells), and uses the cell’s molecular machinery to replicate within them, killing the cells when it is done with each cell. This infection eventually depletes the system of necessary T cells, leaving the infected host helpless to other invading viruses and bacteria. The T cells do have a defense against this, as they have an anti-virus protein in their arsenal – called APOBEC3 – which has the ability to block the HIV cell’s replication process. If they are successful, they can effectively stop the virus from replicating and eventually clear it from the system as the virus cells die off. Unfortunately, HIV has developed a counter-attack to this protein, a protein of their own – called Vif – which attach themselves to the APOBEC3 cells and trick the T cells into destroying their own protein, leaving them defenseless to the virus’s replication and destructive abilities. To learn why some seem to be able to naturally fend off the virus – at least for a lot longer than others – researchers looked closer at these proteins. They found strong clues as to why some immune systems work better against the virus than others.
Some people have a greater ability to create a version of the APOBEC3 protein, which is known as APOBEC3H. This particular form of the protein is boosted whenever someone is infected with HIV, which made the researchers believe this plays an important role in the immune system’s defense against HIV. What they found was a confirmation of this assumption, as people with a more stable accumulation of the APOBEC3H protein seem to be more naturally immune to HIV than those with a more unstable accumulation of this protein. Whenever the infecting HIV cells had a weaker version of their Vif protein (as constant mutations cause the virus to be varied in its strengths and weaknesses), the infected individual with a stable APOBEC3H protein in their T cells had a better time limiting the HIV cells from replicating. This was not the case if the infecting virus cells were equipped with a stronger Vif protein. This discovery helps scientists and doctors with a new path towards attacking HIV, with a possible road to a cure. The more we can suppress the virus’s Vif protein, the more our natural immune system has a chance to combat against the infection. Coupled with a strong antiretroviral regimen, this could help stop the virus from replicating, and possibly killing it outright.