HIV Research
How the Immune System Can Detect HIV
New HIV research has been revealing the workings of the human immune system. The hidden inner workings hold keys to solving some of the most formidable infections facing humankind. One such unlocked mystery is the discovery that one of the immune system’s sensor cells – cGAS – can detect HIV-1.
The cellular molecule, cGAS, is what sounds the alarm when there is an invasion of foreign matter. It has been believed, up until now, that cGAS could not detect retroviruses (such as HIV-1) because of the structural design of its DNA. Human DNA has two strands connected by molecular rungs. Retroviruses have just one strand. Researchers, therefore, concluded that this was one reason the body has trouble ridding itself of the intruder.
The HIV1 can, however, join together. They do this by twisting around each other to form a double strand. While these are more likely to be detected, the strand is often too short and passes through the cGAS radar. Here, however, is where the next piece in this chess game comes into play. The molecular building blocks of these DNA strands, called guanosines, can be detected by cGAS. It does not matter whether the HIV-1 is in its single-strand mode or not. Actually, it hardly mattered at all. What triggered the greatest immune response was the amount of guanosines. When more was added, the cellular defense response increased significantly. This strong reaction declined when the amount was lessened and all but stopped when it was removed altogether.
When HIV-1 infects a body, it imposes its DNA onto the healthy cell’s DNA. The result is a DNA that is curiously lacking in guanosines. It could be a reason as to why HIV-1 is particularly adept at cloaking – being virtually undetected by its host. However, some patients present with such a high number of HIV DNA that the guanosines that do remain still alert the cells, and the defense systems are activated. In these instances, the virus can remain suppressed indefinitely. This strong immune response is believed to be because of the detection of these all-important guanosines and the sensitive radar that detects it, cGAS.
Antibodies in the Future of HIV Treatment
Antibodies, also known as Y-shaped proteins produced by plasma cells, play an important role in keeping us healthy and free from infection. Now, HIV research scientists have identified a protein known as bNAbs. It stands for ‘broadly neutralizing antibodies’ and it may hold the promise of preventing HIV infections. The virus has spikes on it – not unlike many villains – and it uses these to bind and take over healthy cells.
The envelope spike or protein is the preferred target for the bNAbs. They are well equipped to recognize and subdue the virus. However, each type of bNAb is programmed to target specific epitopes or antigens on the spike. Certain bNAbs, therefore, have greater success in suppressing the virus than others. What most known bNAbs do have in common is that they tend to recognize the envelope spike in its closed position.
A virus will attach itself to a healthy cell, but in doing so the spike will open and close – depending on the stage it’s in. One lab has discovered a particular bNAb that can detect the virus when the spike is closed but also when it is partially opened. It was found while the research team was studying the antibodies of those whose bodies successfully control the HIV infection on their own. What is this special antibody called? 8ANC195. Continued efforts to see how 8ANS195 does what it does may lead to big things.
This could prove extremely beneficial in aiding those who are battling with HIV infection. These bNAbs could prove invaluable in identifying and neutralizing HIV that has gone undetected by the immune system. Seeing as most bNAbs target the virus when the envelope spike is closed, the virus with an open spike is free to continue unhindered. Now, with the discovery of antibodies that can detect the virus in its different forms, treatments can be more effective.
For HIV research, the promise of hope offered by these special bNAbs comes with more good news – it could be available in treatments in a short period of time. Clinical trials are already under way. Also, plans to make the antibodies even more effective are in the works. Researchers feel that introducing this bNAb to the cocktail will enhance the treatment therapies currently used.
Genetics May Account for Some HIV Drug Failures
When anti-HIV drugs fail to suppress the condition or prevent transmission, the situation is usually blamed on a patient who does not take the treatment as is needed for it to work correctly. Recent research, however, shows that some individuals, and even some parts of the body may be genetically predisposed to treatment failure.
Consider the drug Tenofovir. It is on the market under the brand name Viread, and the FDA approved this medication back in 2001 as an HIV treatment. Then in 2012 approval was given for use as an oral prophylactic, this time with the goal of preventing HIV transmission.
Unfortunately, some people, and also some parts of the body, have enzymes that take the active Tenofovir and return it to an inactive state that does not combat HIV. The research showed different enzymes to be at work in the vagina and rectum causing the treatment to have different results depending on where it was used on the body. But even when used in the same manner, results still varied.
That is because the location of the treatment was not the only determining factor. About one in 12 women who were part of the study suffered from a genetic variation that rendered the medication inert regardless of how it was used.
Learning this is a big step for researchers since it was previously just assumed that human error was involved when the drug didn’t work. Now the realization is that genetics may be involved. The next stage of research may reveal that genetic testing can determine in advance if Tenofovir is a viable treatment option or not for a particular individual.
The next step is a clinical trial. It is hoped that such continued research will determine how anti-HIV drugs function and what variants definitely affect how successful the treatment will be from person to person.
Research Shows Why HIV Progresses Faster in Some
A study was performed to determine why HIV is able to evade the efforts of current HIV treatments and persist in the body. This study will lead to improved HIV prevention. Let’s look at a breakdown of the HIV genetic code and what researchers found which may eventually lead to better treatments.
Researchers understand the way HIV spreads within the body. In order for HIV to enter a host cell, there is a sort of viral envelope. This envelope contains two glycoprotein molecules that have been named gp41 and gp120. The gp120 molecule has been further studied and broken down into sections that have been labelled with either a C or a V and the numbers 1 through 5.
In turn, this genetic code tells the virus to use the R5 receptor to enter a CD4 immune cell. This entry point is the focus of most HIV drugs. However, in about half of patients the virus will avoid using the R5 entry point and switch to the X4 receptor. This change results in a worsening of the disease and difficulty treating HIV with currently available medications.
Previous research made it seem that the gp120’s V3 region was the part that was solely responsible for this change and progression in how the disease spreads within the body. While the V3 region does clearly play a role, a minute genetic change in the gp120’s C2 region also comes into play. This genetic change, though slight, could prove to be an important discovery for researchers.
Now, it is up to researchers to figure out how to put this knowledge to use in combating HIV’s ability to progress despite treatment. It is hoped that the additional knowledge as to how the disease changes which receptor it focuses on will result in finding ways to predict progression and find a way to develop better means for HIV prevention and treatment.
HIV Outbreaks Spur Calls for Lifting Needle Exchange Ban
The drug scene in this country is changing and not for the better. Injection drug users are on the rise, just not where most expected. What was once contained and limited to larger, populated areas is now spreading to the most rural backdrops. Due to this surge, HIV outbreaks have been sprouting in what some would have considered, unlikely regions. Take for example a small agricultural county in Indiana.
This small county, bordering Kentucky, averaged just a few cases of HIV per year in the past. In the first half of this year, however, 169 new cases were reported – a drastic change. To add to that, 80% of those infected with HIV have been infected with Hepatitis C as well.
Experts long feared that this shift in demographic would bring about these tragic consequences. Drug abuse is now common among rural, predominantly white areas. Another alarming statistic shows that the number of male and female abusers are about equal. Along with injecting drugs comes the increased risk of spreading HIV. While proven methods in the past have effectively faced these challenges, one such method has a federal funding ban on it. Needle exchange programs worked well in the past to ensure that those who used needles would not pass them on to other users. A filled prescription for a needle could be refilled once the used needle was returned. It is a simple concept, but it worked and worked well.
The issue at hand is that there is currently a ban on federal funding for these programs. Without funding, the programs cease to run. Anyone with needle prescriptions can simply toss or pass along the used item. It is precisely these actions that have health officials worried that more HIV outbreaks in small communities will be making headlines. The call now is for a lift on this ban in hopes of stemming the changing tide.
As for the small Indiana community, the state governor has allowed funds to go into the needle exchange program for that county. The rest of the state will not be receiving the same benefits. The funding for each county is conditional: that is, based on need.