A recent study among HIV patients has found that an genetic background of heart disease seems to have more affect on the likelihood of developing coronary artery disease than other risk factors such as high cholesterol. It has also been shown that the anti-retrovirus drugs used to treat HIV patients will increase the likelihood that HIV patients will develop coronary artery disease.
According to the study genetics and anti-retroviral drugs are both just as likely to cause coronary artery disease. This information is very important to the treatment of HIV patients. The researchers believe that doctors should be collecting genetic on HIV patients in order to correctly determine the likelihood that the patient will develop coronary artery disease.
It is important to note that recent studies have found that HIV is linked to the development of heart disease. It is thought that this may be due to the inflammatory effects of the disease. However, the side effect from anti-retrovirus drugs has also been shown to be a major contribution.
The researchers believe that HIV patients must be closely monitored due to the anti-retrovirus drugs. However, they believe that in HIV patients who also have genetic history it may be appropriate to use more aggressive treatments before the coronary artery disease even develops.
Genetics have also been shown to play a large role in patients without HIV as well. Do you think it is okay to treat a disease before it has developed as the researchers in this study would like to do?
Original Article- http://www.aidsmap.com/Genetics-make-a-large-contribution-to-cardiovascular-risk-for-people-with-HIV/page/2635767/
Genetics in Heart Disease- http://usatoday30.usatoday.com/news/health/2004-12-22-cardiac-genetic-link_x.htm
An article in ScienceDaily says that the researchers at Albert Einstein College of Medicine have figured out how regulation occurs of the protein that blocks HIV-1 from multiplying in white blood cells. HIV-1 is the virus that causes AIDS and this discovery could serve as a potential elimination of the virus. It can eliminate the residue of the HIV-1 that remains in patients that have undergone antiretroviral therapy which reduces HIV-1 levels in the blood until it is undetectable, but it still remains in the phages. Dr. Felipe Diaz-Griffero says, “If you stop antiretroviral therapy, the virus emerges from these reservoirs and returns to the general circulation in a matter of days, as if the patient had never been treated.” Now that they have identified the protein and its regulation, they can prevent the HIV-1 from arising form reservoirs, eliminating them completely. Scientists have always known that the protein is SAMHD1 but they have never been able to figure out why it only prevents HIV-1 replication in certain cells but not other crucial ones such as macrophages. SAMHD1 exists in two forms: phosphorylated and unphosphorylated. A cell is only protected from the replication of the HIV-1 when there is unphosphorylated SAMHD1 proteins present. They are now trying to figure out a way to permanently keep SAMHD1 in its unphosphorylated state.
T-cell Infected by HIV
I think this is a great discovery in science. It can potentially lead to a cure of a disease that people have been searching for the longest time. It would be a great success in medicine if this technique could be introduced to the public. However, I am curious to know how they will be able to account for the differences that exist from patient to patient.
In a world where an estimated 300,000 newborns are delivered already infected with HIV, it is safe to say that any progress in stopping this epidemic would be considered remarkable. On March 3, 2013, it was finally announced that a young baby from Mississippi had allegedly been cured of HIV maternally transmitted while in the womb. If confirmed, this will be only the second documented cure of HIV in the entire world. Contrary to normal “prophylactic measures,” this baby was immediately placed on a rigorous three-drug combination antiretroviral therapy directly following post-delivery HIV testing. Initially at the University of Mississippi Medical Center, the baby tested HIV positive for 5 tests (4 viral RNA and 1 DNA). Two blood tests ordered hours apart to ensure further reliability revealed that the baby’s HIV viral levels were about “20,000 copies per milliliter.”
At 1 month old, the baby’s HIV levels were steadily decreasing in response to the rapid treatment. When the toddler reached 18 months, it was brought back to UMMC for further medical testing and viral assessment. To doctors’, nurses’, associated staff’s and the mother’s great surprise, all tests returned HIV negative.
The researchers, sponsored by amfAR, the Foundation for AIDS Research, put the baby through a battery of sophisticated tests. They found tiny amounts of some viral genetic material but no virus able to replicate, even lying dormant in so-called reservoirs in the body.”
Although skeptics unfortunately question the facts of this case, it has been hypothesized by many health professionals that the virus of this child was treated in such a rapid fashion that it did not have time to manifest into these “hidden reservoirs” of the body. For those plagued with HIV, the virus typically hides in a dormant state within reservoirs and is able to resist medication. Other doctors now contest the fact that this is a true cure if the child never actually established this “hiding areas” for the virus to hide and grow. Regardless, the results of this child’s case may prove of substantial importance in the innovation of future treatment of HIV and can serve as a heartwarming sense of hope for those longing for a cure.
[For more on this article, check out the following links: http://www.nytimes.com/2013/03/04/health/for-first-time-baby-cured-of-hiv-doctors-say.html?pagewanted=2&_r=0&hpw & http://abcnews.go.com/Health/mississippi-baby-born-hiv-functionally-cured-doctors/story?id=18645410]
In a recent article published in Science Daily discusses how we might have a potential cure for HIV. Researchers in UCLA were able to test engineered stem cells in mice, that were able to decrease the levels if HIV in blood. The stem cells were engineered to become multi-functional HIV specific CD8 cells that only target HIV, not being able to damage any other part of the body.
In the study there was a slight weakness: “Human immune cells reconstituted at a lower level in the humanized mice than they would in humans, and as a result, the mice’s immune systems were mostly, though not completely, reconstructed.” In order to solve this dilemma; the scientists can use multiple forms of T-cell receptors, to compensate for high levels of HIV mutation in humans.
Human stem cells are very controversial in modern science. They have been used for many different things that some do not agree with, but everyone can agree that finding a cure for HIV would be a miracle. This miracle may actually be possible with the use of stem cells. At UCLA, a team of researchers have shown that genetically engineered stem cells can attack HIV-infected cells in a living organism.
This group of researchers were able to use stem cells in order to make a higher quanitity of CD8 cytoxic T lymphocytes. These new cells were made to target any cells containing HIV proteins. This new study was tested on mice in order to prove that it was actually possible. After giving the HIV infected mice the new genetically engineered cells, weeks later it was found that there were more and more T lymphocytes and less HIV in the blood. This may mean that the possibility of finding a cure to HIV is possible, and we may be closer than we thought.
A team of researchers at UCLA, led by Scott G. Kitchen, who is an assistant professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA, have demonstrated that human stem cells that have been genetically altered into HIV-fighting cells can actually be used in living organisms to attack HIV-infected cells. The research team at UCLA, knowing that CD8 cytotoxic T lymphocytes of the “killer” T cells are able to destroy the HIV-infected cells but are not sufficient enough in numbers to destroy all of the HIV-infect cells to clear the body, have discovered a way to clone the receptor cells which has allowed them to genetically engineer human blood stem cells. They made this discovery by implanting human thymus tissue, which they have injected with the human stem cells, into mice. This allowed the research team to study the reaction that the human stem cells had inside of a living organism. They discovered that the human stem cells developed into HIV-specific CD8 cells that could attack the cells that contained the HIV proteins, but in doing so realized that the T cell receptors need to be matched to an individual. The mice were tested two and six weeks after being introduced to the engineered human stem cells and concluded that the steam cells were capable of developing and fighting the infections. The research showed that during these tests the CD4 “helper” T cells had increased and the HIV infected cells had decreased. They concluded with a potential weakness that HIV- infected cells may be less likely to attack mice cells as quickly as humans so this could be one way to account for a possibly higher mutation rate of the HIV cells in humans.This is still a great first step in correcting the defects of the human T cell with regards to HIV infected humans.
In an article from Medical News Today, United States scientists in Los Angeles have found engineered human stem cells in mice acting against the HIV virus. This team had previously discovered that it was possible to create cells that find and kill the virus, but this was the first time that it was done in a living organism. Researchers now believe that human stem cells can help to push viruses down to very low levels among the population and will overall “engineer the human immune response to combat viral infections” (Medical News Today). Although this experiment has come a long way to reach such a great discovery, this will begin a very long journey to be able to use this in every day life with humans. Scott G. Kitchen who was the lead investigator of this study, plans to contain HIV and white blood cells (T cells) that target pathogens in the body until he finds a way to have the T cells successful destroy the HIV virus. Within the mice, it was found that “helper” T cells increased in the blood while HIV decreased.
If this study is proven to be successful and down the road becomes a treatment for anyone, millions of lives would be saved. Not only will this help the HIV virus to a minimum in the human population, but it will also help to open the door to solving many other diseases with unknown treatments, such as cancer.
Medical researchers are now seeing that curing AIDS may be possible thanks to the positive outcomes of two patients. The article says that the first patient cleared his infection through bone marrow transplants. The second patient, a 50-year old man, although not yet cured, was able to briefly control the virus while being off of drug treatment by undergoing a a simpler gene therapy procedure. In the past, there have been attempts to cure HIV, however most experts found it more efficient to focus on prevention and treatment. Such treatment has effectively changed HIV from being a deadly disease to being a chronic disease. The treatment does not eliminate the disease, and if the infected patient were to stop taking the antiviral drugs, the virus would come “roaring back”. Dr. Steven Deeks, professor of medicine at the University of California, San Francisco, said that he does not think the world has the resources to provide these daily drugs to the tens of millions of infected people for decades. Therefore a cure for the disease is becoming increasingly more vital. Grants totaling over $70 million are now being awarded to research teams with the intentions of finding a cure. It is expected to take years to find a cure, if at all, but it was said that they are closer to finding a cure than a vaccine.
There are two approaches being taken. The first being a sterilizing-cure, wiping out all traces of the virus from the body, like the first patient. The second being similar to the case of the 50-year old man, where the virus would not be eliminated but it would be possible to control the virus without taking the antiviral drugs daily.
The first patient’s elimination of the cancer was circumstantial. While receiving bone-marrow transplants to treat his leukemia, he received an immune system resistant to the virus because the donor had lacked a protein, CCR5 which is on the surface of immune cells and is the entry point for the virus. This cleared the virus out of the patient’s system. Bone marrow transplants are painful, risky, and expensive so this procedure could not be used as an ultimate cure. There is also the problem of finding immunologically matching donors and a donor with the rare mutation in the CCR5 gene. However, this case has built on the idea of finding a way to modify patient’s immune cells to make them resistant to infection by eliminating CCR5.
This was what was done with the second patient. The man’s white blood cells were treated with gene therapy to disrupt the CCR5 gene. A month later he was taken off his antiviral medication. The HIV in his blood shot up at first but by the end of 12 weeks fell down to an undetectable level again and his immune cell counts increased. His success might have been due to having an inherited mutation in one of his CCR5 genes already because the gene therapy did not work so well for 5 other patients. What was learned from the case however was that it could take freeing as little as 10 percent of the main immune cells infected by the HIV from the virus to control it since a vast majority of the patient’s cells were not genetically altered.
There is currently being research and work done on disabling the CCR5 genes in blood stem cells. This would make the entire immune system resistant to the virus although it would require a stem cell transplant.
Medical researchers may now be back in pursuit of what was thought to be an unachievable goal: curing HIV. One man from San Francisco may have done what was thought to be impossible, cleared his body of any detectable signs of HIV. The treatment is several bone marrow transplants. Hope for the cure was raised in part by the experience of the patient, an American named Timothy Brown who had both HIV and leukemia.
In 2007 and 2008, while living in Berlin, Mr. Brown received two bone-marrow transplants to treat his leukemia. The donor was among the 1% of Northern Europeans naturally resistant to HIV infection because they lack CCR5, a protein on the surface of immune cells that the virus uses as an entry portal. With his own immune system replaced by one resistant to infection, Mr. Brown, 45, has apparently been free of the virus for about four years. There is a downside to this new discovery, however. Bone marrow transplants are grueling, risky and expensive. Moreover, it is hard enough to find an immunologically matching donor, let alone one with mutations in both copies of the CCR5 gene. There is still hope for gene therapy in HIV patients. The therapy inducesthe cells to produce proteins called zinc-finger nucleases that can disrupt the CCR5 gene.
While currently there is no definite path to a safe, marketable cure, hope lies on the horizon for those suffering with HIV and AIDS.
In 2007, a man in Germany donated blood stem cells to an American man living with both leukemia and HIV. The transplant cured both diseases apparently due to the donor’s immunity to HIV. This report can be found here. About 1% of white people and less of minorities are immune to the virus. This article reports on promising follow up research from this discovery.
The rare immunity is due to absence of both copies of the CCR5 gene which creates a protein receptor where the HIV virus normally would enter. Sangamo BioSciences Inc., in California has produced a treatment which deletes exact portions of DNA, permanently erasing a gene, like the one which codes for the protein receptor, CCR5. The treatment was carried out on 6 HIV positive individuals and the result was that their blood was maintaining and reproducing the resistant cells- up to 6% of their total T-cells, were now resistant to HIV a year after initial infusion. It is still unknown if the treatment carries risks or if it will need to be redone in the future. The goal of this is that people will not have to take the massive amounts of medicine to survive. So far the results are outdoing expectations it seems. We may be on the path to a cure.
HIV virus
