HIV antibody discovered that binds to novel target on virus

An NIH-led team of scientists has discovered a new vulnerability in the armor of HIV that a vaccine, other preventive regimen or treatment could exploit. The site straddles two proteins, gp41 and gp120, that jut out of the virus and augments other known places where broadly neutralizing antibodies (bNAbs) bind to HIV. This newly identified site on the viral spike is where a new antibody found by the scientists in an HIV-infected person binds to the virus. Called 35O22, the antibody prevents 62 percent of known HIV strains from infecting cells in the laboratory and is extremely potent, meaning even a relatively small amount of it can neutralize the virus.

Following their discoveries, the scientists found that 35O22-like antibodies were common in a group of HIV-infected people whose blood contained antibodies that potently neutralized a broad array of HIV strains. According to the researchers, this suggests that it might be easier for a vaccine to elicit 35O22 than some other known bNAbs, which are less common.

Since 35O22 binds only to forms of the viral spike that closely resemble those that naturally appear on HIV, the scientists believe a vaccine that elicits 35O22-like antibodies would need to mimic the natural shape of the spike as closely as possible. This would require a different approach than that used in many previous experimental HIV vaccines, which have included just parts of the viral spike rather than a structure that looks like the entire native viral spike.

In addition, the researchers report, the HIV strains that 35O22 neutralizes complement strains neutralized by other bNAbs. This suggests that eliciting or combining 35O22 with a few other bNAbs in a vaccine or a prevention or treatment regimen could likely neutralize the vast majority of HIV strains found around the globe, according to the scientists.

Tolerating, not fighting, viruses a viable survival strategy

In ecology, disease tolerance is defined as a host strategy not to fight a pathogen tooth and nail, but rather tolerate it to live (and survive) better in the long term. One key feature of tolerance is that the disease only progresses very slowly - if at all - even if the host carries a high pathogen load.

Roland Regoes, a senior scientist at ETH Zurich's Institute of Theoretical Biology, has now transferred this approach to HIV. He set about investigating whether there are infected people who are more tolerant of the HI virus than others and if so which factors this tolerance depends upon.

Regoes came up with the idea for the study during his postdoctoral stay in Atlanta, where he was working with researchers from a large primate centre. They studied sooty mangabeys (Cercocebus atys) infected with SIV, an HIV-like virus that affects primates. Although a large amount of the SI virus was found in their blood, some of the monkeys did not become ill. "The infection in this primate species is one of the best examples of disease tolerance," says the researcher. He and his co-authors -- all medical doctors -- are now interested in whether the concept of tolerance can also be carried over to human diseases. In order to determine which factors are linked to tolerance, the scientists evaluated the data from the Swiss HIV Cohort Study statistically.

Their analyses revealed that certain patient groups are more tolerant of HIV than others. For instance, the twenty-year-old group is more tolerant than sixty-year-olds, with the disease developing 1.7 times more rapidly in older patients than in their younger counterparts.

The same goes for the group of patients whose HLA-B genes come in two different variants. HLA-B genes are a group of genes which facilitate immunity to the HI virus. Every person has two copies of every gene, which do not have to be identical. If they are not, this is referred to as heterozygosity. If both HLA-B variants are identical, i.e. homozygotes, the tolerance of the virus is considerably lower.

Certain HLA-B variants are known to facilitate an immune defence against the virus geared towards its destruction. These variants are not responsible for tolerance. Instead, tolerance is linked to combinations of other HLA-B variants.

Regoes and his co-authors did not find any difference in tolerance between genders. The ETH-Zurich researcher recorded roughly the same high values in women and men, although on average women exhibit lower initial viral loads than men.

For his analyses, Regoes used the number of particular immune cells, the CD4+ cells, on the one hand and the viral load during the asymptomatic phase on the other. The latter is a key quantity in HIV infection. As soon as the virus infects someone, it multiplies rapidly and heavily before the immune system reduces its number to a certain level. From then on, the immune system keeps the pathogen relatively well under control for a long time. However, the number of CD4+ cells drops continuously until it reaches a critical level. If the number of these immune cells falls below 200 per millionth of a litre of blood, AIDS breaks out. The researchers calculated the tolerance of HIV sufferers to the virus from the correlation between the rate at which the CD4+ cells decreased and the viral load during the asymptomatic phase.

Tolerance and resistance are alternative but complementary defence strategies deployed by a host to combat pathogens. In the case of tolerance, it is not the destruction of the adversary and thus the reduction of the viral load that is the priority, but rather the alleviation of the negative effects of the infection for the host. This is not tantamount to capitulation. Instead, the strategy ensures that the evolutionary race between the parties cools off. "It is heading in the direction of commensalism," says Regoes -- a kind of ceasefire between two disparate partners. However, the two strategies have different evolutionary consequences: while tolerance tends to suppress the emergence of adaptations, resistance challenges the adaptability of viruses, which results in an evolutionary arms race with the adversaries.

"In the long run, one could try to use this ceasefire therapeutically," says the ETH-Zurich researcher. Tolerance-based therapeutic strategies could constitute interesting alternatives as they are not expected to lead to treatment-resistant pathogens.

Complexities of reducing HIV rates in Russia

Decreasing HIV transmission among Russian HIV-infected drinkers will require creative and innovative approaches, results of a new study conducted in St. Petersburg, Russia, show. While new HIV infections globally have declined, HIV rates remain high in Russia. This is due in large part to injection drug use and spread via heterosexual sex transmission.Results of a new study conducted in St. Petersburg, Russia, show that decreasing HIV transmission among Russian HIV-infected drinkers will require creative and innovative approaches.

While new HIV infections globally have declined, HIV rates remain high in Russia. This is due in large part to injection drug use and spread via heterosexual sex transmission. Alcohol use also has been shown to be related to risky sexual behaviors and sexually transmitted infections (STIs).

The study showed that a behavioral intervention did not lead to a reduction of STIs and HIV risk behaviors in Russian HIV-infected heavy drinkers when compared to the control group. This study was led by researchers from Boston University School of Medicine (BUSM), Boston Medical Center (BMC) and First St. Petersburg Pavlov State Medical University, Russia.

In this study, the researchers adapted a Centers for Disease Control and Prevention-best evidence risk reduction intervention for a Russian clinical setting and assessed its ability to reduce STIs and HIV risk behaviors among 700 HIV-infected heavy drinkers. The intervention stressed disclosure of HIV serostatus and condom use in two individual sessions and three small group sessions. Participants had a laboratory test at a 12-month follow up appointment to determine if they had contracted STIs. They also answered questions about risky behaviors, including unprotected sex, drinking alcohol or injecting drugs.

At the 12-month follow-up assessment, STIs occurred in 20 subjects (8 percent) in the intervention group and 28 subjects (12 percent) in the control group. Both groups, however, reported having decreased their participation in risky behaviors.

"Addressing prevention of HIV transmission from HIV-infected Russian drinkers, a group at particularly high risk for disease transmission, requires creative approaches and aggressive uptake of antiretroviral therapy," said Jeffrey Samet, MD, MA, MPH, professor of medicine at BUSM and chief of the section of general internal medicine at Boston Medical Center. "This study shows that we need to explore other options to help stem the growing epidemic.".

Why HIV patients develop dementia

HIV-associated neurocognitive disorders" (HAND) include disorders of the cognitive functions, motor capacities as well as behavioural changes. How exactly HAND occur has not, as yet, been fully understood. "Scientists assume that HIV is harmful to cells directly and that is also triggers indirect mechanisms that lead to nerve cell damage," explains Dr Simon Faissner (RUB clinic for neurology, St. Josef-Hospital).

The researchers strongly suspect that, once activated in the brain and the spinal cord, immune cells keep up a chronic inflammation level which then results in the destruction of nerve cells. An immune activation in peripheral tissue as well as therapeutic consequences may likewise contribute to nerve cell damage in the brain.

The HIV virus overcomes the blood-brain barrier hitchhiking on infected immune cells, the monocytes and probably the T cells. The researchers from Bochum tested the hypothesis that HIV-infected monocytes activate specific immune cells in the brain, the so-called microglial cells. These cells, in turn, respond by releasing harmful substances, such as reactive oxygen metabolites and inflammatory signalling molecules, i.e. cytokines. To test this hypothesis, the researchers developed a cell culture system in which they initially examined the effect of HIV-infected monocytes on microglial cells. The researchers simulated the individual steps of HIV infection and measured the volume of the cytokines released at each stage. Thus, they were able to demonstrate that releasing the viral RNA in the monocytes was a sufficient trigger for maximal microglial activation. Subsequent infection phases -- reverse transcription into DNA and the resulting formation of HIV proteins -- did not augment activation any further.

In the second step, they analysed nerve cells from rat brains to determine if the substances released by the microglial cells could lead to cell death. Compared with the control group, the number of cell deaths was indeed twice as high. Studies of liquor cerebrospinalis received from HIV-infected patients have shown a positive correlation with marker of neuronal degeneration in patients who did not as yet present any neurocognitive disorders. Detailed understanding necessary for therapeutic strategies

"Thanks to our research, we have gained a better understanding of the mechanisms of HIV-associated neurodegeneration," concludes Prof Dr Andrew Chan. "These results are likely to contribute to HAND biomarkers becoming established. In the long term, these data will be used to develop therapeutic strategies aiming at retarding HAND progression in HIV-infected patients." Starting points may include activation of microglial cells -- a method that is applied in other autoimmune diseases of the central nervous system, for example in multiple sclerosis.

Gut flora influences HIV immune response

Normal microorganisms in the intestines appear to play a pivotal role in how the HIV virus foils a successful attack from the body's immune system, according to new research.

The study builds on previous work from researchers at the Duke Human Vaccine Institute that outlined a perplexing quality about HIV: The antibodies that originally arise to fight the virus are ineffective.

These initial, ineffective antibodies target regions of the virus's outer envelope called gp41 that quickly mutates, and the virus escapes being neutralized. It turns out that the virus has an accomplice in this feat -- the natural microbiome in the gut. "Gut flora keeps us all healthy by helping the immune system develop, and by stimulating a group of immune cells that keep bacteria in check," said senior author Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute. "But this research shows that antibodies that react to bacteria also cross-react to the HIV envelope."

Haynes said the body fights most new infections by deploying what are known as naïve B cells, which then imprint a memory of the pathogen so the next time it encounters the bug, it knows how to fight it.

But when the HIV virus invades and begins replicating in the gastrointestinal tract, no such naïve B cells are dispatched. Instead, a large, pre-existing pool of memory B cells respond -- the same memory B cells in the gut that fight bacterial infections such as E coli. This occurs because the region of the HIV virus that the immune system targets, the gp41 region on the virus's outer envelope, appears to be a molecular mimic of bacterial antigens that B cells are primed to target. "The B cells see the virus and take off -- they make all these antibodies, but they aren't protective, because they are targeted to non-protective regions of the virus envelope."

Haynes and colleagues said the findings were confirmed in tests of people who were not infected with HIV. Among non-infected people, the researchers isolated mutated gp41-gut flora antibodies that cross-react with intestinal bacteria.

"The hypothesis now is that the gp41 antibody response in HIV infection can be derived from a pre-infection memory B cell pool triggered by gut bacteria that cross-reacts with the HIV envelope," said lead author Ashley M. Trama. "This supports the notion that the dominant HIV antibody response is influenced by previously activated memory B cells that are present before HIV infection and are cross-reactive with intestinal bacteria."

Haynes said the finding provides compelling new information for HIV vaccine development, which is the next phase of research. "Not only can gut flora influence the development and function of the immune system, but perhaps also pre-determine our reaction to certain infections such as HIV," Haynes said.

AIDS and Seniors

HIV (short for human immunodeficiency virus) is a virus that kills cells in your immune system, the system that fights diseases. Once your immune system is weakened to the point where you get certain types of life-threatening diseases, infections, and cancers, you have what is called AIDS or acquired immunodeficiency syndrome. AIDS is the most advanced stage of HIV infection. If there's any chance that you might be infected with HIV, you should be tested because now there are drugs you can take to help your body keep the HIV in check and fight against AIDS.

Many people do not have any symptoms when they are first infected with HIV. It can take as little as a few weeks for minor flu-like symptoms to show up or as long as 10 years or more for more serious symptoms. Symptoms can include headache, chronic cough, diarrhea, swollen glands, lack of energy, loss of appetite and weight loss, frequent fevers and sweats, frequent yeast infections, skin rashes, pelvic and abdominal cramps, sores on certain parts of your body, and short-term memory loss. People age 50 and older may not recognize HIV symptoms in themselves because they think what they are feeling and experiencing is part of normal aging.

Anyone can get HIV and AIDS. Regardless of your age, and especially if you are 50 years old or older, you may be at risk for HIV if any of the following is true:

• If you are sexually active and don't use a male latex condom. You can get HIV/AIDS from having sex with someone who is infected with the HIV virus. The virus passes from the infected person to another through the exchange of body fluids such as blood, semen, and vaginal fluid. HIV can get into your body during sex through any opening, such as a tear or cut in the lining of the vagina, vulva, penis, rectum or mouth.
• If you don't know your partner's sexual and drug history. Has your partner been tested for HIV/AIDS? Has he or she had a number of different sex partners? Does your partner inject drugs?
• If you inject drugs and share needles or syringes with other people. Drug users are not the only people who might share needles. People with diabetes, for example, who inject insulin or draw blood to test glucose levels, might share needles. If you have shared needles for any reason or if you have had sex with someone who has, you should be tested for HIV/AIDS.
• If you had a blood transfusion between 1978 and 1985, or a blood transfusion or operation in a developing country at any time.
• If any one of the above is true, you should be tested for HIV/AIDS. Check your local phone directory for the number of a hospital or health center where you can get a list of test sites. In most states the tests can be confidential (you give your name) or anonymous (you don't give your name).

There are many myths about HIV/AIDS. The examples below are facts:

1. You cannot get HIV through casual contact such as shaking hands or hugging a person with HIV/AIDS.
2. You cannot get HIV from using a public telephone, drinking fountain, restroom, swimming pool, Jacuzzi, or hot tub.
3. You cannot get HIV from sharing a drink or being coughed or sneezed on by a person with HIV/AIDS.
4. You cannot get HIV from donating blood
5. You cannot get HIV from a mosquito bite.

What Are The Real Chances Of Finding Cure For HIV?

Human Immunodeficiency Virus (HIV) is behind the largest and deadliest pandemic in the recent human history. In 2011, 34 million people were living with HIV worldwide. In our age of advanced medicine, the situation when infectious disease spreads seemingly out of control is very rare. For the majority of common infectious diseases we have either medicine capable of curing them, or at least, medication making them manageable. Also, preventive measures such as vaccinations allow to put most infections under control. But effective therapeutic management is now available. HAART (Highly Active AntiRetroviral Therapy) helps to eliminate the most of virus from the body of infected person, thus reducing to the minimum his or her chances to develop AIDS and suffer any other infection-related health problems. In fact, people receiving the antiretroviral therapy can now expect to live almost normal life, and their average life expectancy is almost the same as in the healthy population.

Advantages And Problems Of Modern Antiretroviral Therapy

Modern drugs effectively reduce the level of virus in the blood (viral load) to almost undetectable level. The decrease in viral load not only improves the immune system of the patient but also decrease the risk of HIV transmission to healthy people. The price to pay - take a pill every day. Like any other chronic disease, HIV needs to be treated by drugs on a daily basis. And there is always a danger of developing drug resistance thus making the medicines ineffective. On top of this, drugs do have both short-term and long-term side effects that in some cases can be severe.

Finally, the newest and most efficient drugs are costly and often unaffordable. The price of unsubsidized drug bill can easily reach $30,000 per year.
The problems of living with HIV make the development of cure very desirable. Lots of research is being done worldwide in the pursuit of this goal. But how achievable is this target? Can we expect any real breakthrough that is so eagerly anticipated by millions of infected people? Although modern HAART therapy is hailed as a great success, the cure of HIV remains an elusive goal. There were, however, several reports of so-called functional cure of HIV infection in several individuals.

One HIV-positive patient received the bone marrow transplant from a donor with a rare natural genetically programmed resistance to HIV infection. The monitoring of this patient so far did not reveal any signs of disease return. He was declared completely free from HIV thus making him the first ever person to be cured of the disease.

Another very recent report described the case of a newborn baby who got infection from mother. Therapeutic intervention with HAART has started almost immediately after the baby was born and seemed to be successful in completely elimination of virus.

Obviously, the above strategies are not viable for the overwhelming majority of patients. Something else has to be done.

Complete Cure For HIV Is Difficult But Not Impossible To Achieve - The problem lies with the mechanism of drug action: all modern drugs are active only against the actively replicating virus. The virus does become silenced in some situation. For example, the host cells of immune system can become dormant and shut down almost all replication mechanisms. In such cells virus can stay without showing any activity for very long time. As a result, this virus remains completely insensitive to all drugs. Once the cell wakes up, the virus starts to reproduce as well and easily replenish its population in the body if the drugs were discontinued.

There are also so-called anatomical reservoirs of the virus. HIV can hide at different anatomic locations such as gastrointestinal tract and brain of the patients receiving antiretroviral therapy. These sites have various kind of barriers limiting the ability of antiretroviral drugs to reach the infected cells. Again, when the treatment is stopped the virus from these places could cause re-infection. Some researchers hypothesize that HIV can infect certain non-immune cells and survive there in dormant stages for many years.

The logical answer to the problem of latent viruses lurking somewhere in the safe heavens around the body is to get them out of their hiding places. Two major strategies are currently being developed by researchers working in this field. First strategy aims to activate the latent cells of immune system. Activation would also turn on the replication process of the virus .With the virus replicating inside the cell, the cell will ultimately die, and the released viruses could be get rid of using the traditional and highly effective antiretroviral therapy. There are different agents which could potentially help in activating the latent T cells. One such agent, Interleukin-7 (IL7) is currently undergoing clinical trials. Prostratin is another compound that could do this but at present time only limited data is available for its safety profile and efficiency in humans. It will take several years to get enough data and see if these drugs serve the purpose.

The second strategy relies on turning on the HIV genes within the latent cells infected by virus. Histone deacetylase inhibitors (HDACI) seem to be able to do exactly this. These drugs could turn on the gene expression in the viruses present inside the silent T cells thus making them vulnerable for antiretroviral drugs. Further studies are needed to evaluate the efficiency of these drugs.

With the pace of developments in the HIV research, many scientists now believe that the cure for HIV is only few years away. The infection has already proven itself as a very difficult target to treat. Many drugs previously developed with curative intent have failed to their promises.

But this time the level of confidence among scientists and observers is higher than ever. Let’s hope that they are right.

Linking microbial, immune environment in semen to HIV viral load, transmission

While HIV is found in many body fluids, sexual transmission through semen is the most common route of infection. Consequently, the amount of virus in semen (the semen viral load) affects the likelihood of HIV transmission. Besides sperm, semen also contains immune factors and communities of bacteria, an environment that could influence the viral load. Research published on July 24th in PLOS Pathogens reports that HIV infection re-shapes the relationship between semen bacteria and immune factors which in turn affects viral load, suggesting that the semen microbiome plays a role in sexual transmission of HIV.

Researchers led by Lance Price, from the Translational Genomics Research Institute, USA, and Rupert Kaul, from the University of Toronto, Canada, studied the relationship of semen bacteria with HIV infection by analyzing semen samples from 49 men who have sex with men (MSM). They focused on MSM because of the high risk of sexual HIV transmission in this population. 27 of the men were HIV infected, and provided samples both before they started anti-retroviral therapy (ART) and one and six months after. Samples from 22 MSM not infected with HIV served as controls.

In HIV-infected men not on ART, overall numbers of bacteria in the samples -- the semen bacterial load -- was correlated with HIV viral load. Analyzing the bacterial DNA in the samples, the researchers detected a total of 248 unique types of bacteria in semen from the controls, on average 71 different ones per sample. In samples from HIV-infected untreated men, semen microbiome diversity was markedly reduced, and the relative abundance of the more common bacterial groups differed. ART for six months reduced semen viral load to undetectable levels, and restored bacterial diversity and composition to a situation similar to the controls.

There was no correlation in uninfected controls between levels of immune factors and semen bacterial load. In contrast, in HIV-infected men, several factors, and most strongly one called interleukin-1beta (IL-1b), a mediator of inflammation, showed a correlation with both semen bacterial load and semen viral load.

"While delineating the directionality and causality of the complex relationships they observed will require further studies," the researchers say, their data "suggest an interaction between semen microbiome, local immunology, and semen viral load. Higher bacterial load in semen could lead to higher IL-1b levels, which in turn could induce viral shedding, thereby increasing viral load." They conclude that the results "support the hypothesis that semen bacteria play a role in local inflammation and HIV shedding, and that they are a possible target for reducing HIV transmission."

Women living with HIV benefit from 'expressive therapy' intervention

New research from UC San Francisco shows that an "expressive therapy" group intervention conducted by The Medea Project helps women living with HIV disclose their health status and improves their social support, self-efficacy and the safety and quality of their relationships.

"Medication alone is totally insufficient," said the study's first author, Edward L. Machtinger, MD, director of the Women's HIV Program at UCSF. "Over 90 percent of our patients are on effective antiretroviral therapy but far too many are dying from suicide, addiction, and violence. Depression, addiction, and especially trauma are very common and often devastating for women living with HIV but are not being effectively addressed by most clinics. We believe that helping women develop the skills and confidence to tell their stories publicly will reduce their isolation and be the first step towards their becoming genuinely healthy. We partnered with The Medea Project to deliver an effective expressive therapy intervention that starts to address the primary causes of death in our patients."

The Medea Project was founded in 1989 by Rhodessa Jones as a group performance intervention to empower incarcerated women to improve their lives and reduce recidivism. Jones adapted the program to help women living with HIV. The process consists of a series of intensive workshops that culminate in a theatrical performance.

The Medea Project's method focuses on storytelling as a means of healing and empowerment. The storytelling includes talking about and processing other stigmatizing and traumatic experiences in a group setting with the support of other women. In the case of the study, the process included specific prompts given to the women asking how they found out they were HIV-positive and whom they had told about their HIV status. The burden of secrecy was relieved and self-identity could be recast in a more positive light. Then, through public performance, participants felt the power that their stories could have on others and gained both an appreciation for their lives and a desire to unleash their newly found "voices" to change the social conditions that create HIV risk, stigma and trauma.

In the study, eight HIV-positive women and seven HIV-negative women from Medea's core group formed the final performance group that culminated in a professional theatrical run of eight shows seen by more than 1,000 people. None of the HIV-positive participants had publically disclosed their HIV status prior to the study; all disclosed their status during the performances.

"Eddy Machtinger challenged me to take women living with HIV and apply the processes I had used for over two decades with incarcerated women to get them to open up and talk about living with HIV. Sharing is an important process in creating the play and violence is what they talked about the most," said study co-author Rhodessa Jones, director of The Medea Project. "Our data revealed five core themes that described the impact of the intervention on the participants' lives: sisterhood, catharsis, self-acceptance, safer and healthier relationships and gaining a voice.

Importantly, half of the participants reported leaving or avoiding unhealthy or unsafe relationships, a significant impact since we know women living with HIV experience high rates of intimate partner violence," said Machtinger. "Integrating this type of intervention into the primary care of women living with HIV is the first step towards transforming primary care from treatment to actual healing," he said.

The Use of Human Growth Hormone in the treatment of HIV / AIDS

HIV (human immunodeficiency virus) is the virus that causes AIDS (acquired immune deficiency syndrome). The HIV retrovirus may be passed from one person to another when infected blood, semen, vaginal secretions or other bodily fluids come in contact with an uninfected person's broken skin or mucous membranes. People with HIV have what is called HIV infection and are fit and well. Some of these people will develop AIDS as a result of their HIV infection.

Growth hormone is a popular bodybuilding and performance enhancing aid, and the use of recombinant human growth hormone (rHGH, or simply GH) to treat various conditions in HIV infection has been debated with excitement for years. Indeed it is licensed for the treatment of wasting syndrome in advanced stages of AIDS. GH is also a commonly used bodybuilding and performance enhancing drug, which can be purchased on the black market; used to help both muscle anabolism / strength and reduction in body fat levels. Both of these applications have possible significance in the treatment of HIV.

Other than in the treatment of wasting disease, results from the studies using rHGH to treat body changes associated with HIV and/or drugs used to treat HIV have been very favourable. One which has been studied extensively is the use of rHGH in reducing HIV-associated adipose redistribution syndrome (HARS). However, the positive effects of HGH treatment in HIV may be more direct. Several studies have proposed that rHGH may bolster the immune system in ways that might improve clinical outcomes in HIV.

Wasting
Like cancer cachexia, advanced stages of AIDS are characterised by severe muscle wasting and weakness. The reasons for this are because the patient often has a very poor appetite and food intake, as well as there being direct wasting effects from the HIV and some associated diseases which the patient may have, e.g. pneumonia. The patient then enters a downward cycle with diminished strength, poor food intake and further wasting, and it's often this which leads to eventual death.

Both anabolic steroids and rHGH therapy are used clinically to both slow the effects of wasting and to help improve appetite. Both have been shown to prolong life significantly and improve quality of life in advanced stages of AIDS.

HIV-associated adipose redistribution syndrome (HARS)
HARS is a type of lipodystrophy (abnormal distribution of body fat), where there is accumulation of excess truncal fat and visceral adipose tissue, as opposed to regular gynoid (glutes and hips) or android (abdomen) deposition. This is observed in HIV infected people, moreso as virus load increases. Although not a debilitating condition in itself (indeed extra body fat can prolong life if followed by wasting), HARS is unpleasant for the individual, giving reduced confidence in body image; another negative aspect of the disease. rHGH therapy has been shown to significantly reduce HARS, leading to an improved body image, and significant improvement in psychological well-being. Numerous studies have demonstrated the benefits of this, leading to rHGH being licesenced for the treatment of HARS in some countries. It should also be noted that improvement in psychological well-being could also contribute to a positive clinical outcome, in that it reduces the effects of wasting.

Immune system
Of most interest in HIV therapy are the possible benefits of rHGH use on the immune system, since HIV's primary adverse effect is reduction in the immune system. It has been clearly demonstrated that rHGH does benefit the immune system, but the method by which it helps is still under debate. One theory is that rHGH may stimulate renewal of the thymus gland, an important organ in the immune system. This may, in turn, lead to improved immune health in people with HIV. Studies are now examining whether or not renewing thymus tissue leads to better health and longer survival.

The thymus is necessary for developing new T-lymphocytes, which are key immune cells in the defence against disease, and numbers of which steadily reduce in HIV as infection progresses. In particular the thymus gland is involved in the development of CD4+ and CD8+ cells, and it is the CD4+ level which is a very critical marker in HIV outcome. Without some thymus activity, immune reconstitution that produces a wide range of functional CD4+ cells is not believed to be possible. Thus, the state of the thymus in HIV disease and how therapies affect it are of great interest to those researching ways to restore the immune system.

Napolitano et al  researched rHGH and its impact on the thymus in HIV. Doses ranged from 1.5 (4.5IU) to 3.0mg (9IU) per day for 6–12 months in healthy HIV volunteers. After six months, marked increases in thymus mass were noted, beyond what has been seen using anti-HIV therapy alone. This increase was sustained during the course of rHGH therapy and correlated with a higher CD4+ count, suggesting that the thymus is functioning properly and helping make new T-cells, further suggesting a stronger immune system. When rHGH was stopped, there was a loss of thymus mass; however, CD4+ cell count increases seen over the course of therapy were sustained despite this loss of mass.

Napolitano later did a twenty-person study using 3mg (9IU) rHGH a day injected under the skin (subcutaneous injection). This was followed by 1.5mg (4.5IU) rHGH a day for another six months, for a total of one year of daily therapy. Of the 20 volunteers (all of whom stayed on anti-HIV therapy during the study), ten took one year of rHGH according to the schedule described above while the other ten were merely observed. After one year, the group on rHGH stopped therapy and were observed for a second year, while the group who hadn't taken rHGH therapy then started one year of it. The size of the thymus increased in those on rHGH during the first year, but not among the second group. Those on rHGH had a significant increase in thymus mass while those only on anti-HIV therapy actually had a slight decrease.

Also, these increases in thymus size (together with increases in both thymus density and volume) related to marked increases in naïve CD4+ cells (69% increase among those taking rHGH during the first year compared to only 9% increase for those only on anti-HIV therapy), but not naïve CD8+ cells. This was further associated with more pronounced increases in total CD4+ cell counts (19% increase among those on rHGH versus 1% increase among those only on anti-HIV therapy).

Interestingly the most pronounced increase in both naïve and total CD4+ cell counts were seen among those on rHGH with a rise in the hormone IGF-1 (insulin-like growth factor-1) which is also associated with immune function. In subjects with pronounced increase in IGF-1 levels due to rHGH use, naïve cells increased by 95% and CD4+ increased by 25%.

The AIDS Clinical Trials Group (ACTG) conducted a larger 60-person study. One group was given anti-HIV therapy and 1.5mg (4.5IU) rHGH a day for 48 weeks. A second group took anti-HIV therapy alone for 24 weeks, followed by 3mg (9IU) rHGH a day for 24 weeks. By the end of 48 weeks, both groups showed notable increases in naïve and total CD4+ cell counts. The first group took rHGH for a longer period of time but were on a lower dose that took longer to result in CD4+ cell increases. However, people in the lower dose group showed more pronounced increase by week 48 in another measure of recent thymic activity called TREC (T cell receptor excision circles). Seven out of 11 people in the lower dose rHGH group showed increased thymus mass after 24 weeks while seven out of nine showed the same effect after 24 weeks on the higher dose.

Researchers at Imperial and Chelsea and Westminster Hospital in London (2006) administered rHGH therapy in chronic HIV patients in an attempt to reconstitute HIV specific CD4+ and CD8+ T-cell responses. While viral load and CD4+ and CD8+ counts remained unchanged, T-cell maturation and differentiation were significantly enhanced.

In all of these studies, using rHGH related to increases in thymus size and CD4+ T cell counts. Taken together these studies are promising, but they are not studies of effectiveness. Many questions remain unanswered about using rHGH to treat immune suppression in HIV disease. It does seem that there may be little benefit in respect of the immune system when CD4+ level is still at a reasonable level, but when it goes below an acceptable reference range then rHGH therapy may be worth considering. Obviously a high percentage of newly diagnosed patients are already in more advanced stages of the disease as they only present to their doctor when they have symptoms, so these may already have reduced CD4+.

Acute Infections
HIV patients are often more prone to acute infections which may take longer to clear up than in non-HIV individuals. Sometimes these can be associated with poor appetite and weight loss. rHGH therapy may curb rapid weight loss often associated with acute infections in HIV positive people and may also reduce length of infection. Far more research is needed here though.

Fasting lipid profile
HIV patients have been shown to have elevated serum lipids, and dyslipidaemia, i.e. high LDL (bad) cholesterol and low HDL (good) cholesterol with raised total cholesterol and triglycerides. This is associated with anti-HIV drug treatment especially later on in infection. This does increase risk of cardiovascular diseases, and rHGH treatment may improve lipid profiles.

Bone Building
HIV patients may have loss of bone density associated with wasting. Both treatment with rHGH and growth hormone releasing factor (GHRF) have indicated improved bone mass in HIV patients.

Side effects of rHGH treatment
Although we have focused on the promising benefits for rHGH treatment in HIV infection, consideration of possible side effects is important in ensuring an informed decision can be made. Side effects of rHGH therapy include possible joint pain (arthralgia), abnormal growth of the body's extremities and impaired glucose intolerance, increasing the risk of type 2 diabetes.

Caution is also advised against using over-the-counter or faddy internet products that claim to contain human growth hormone. Some of them claim to contain plant-derived growth hormone, others claim to contain cow or goat growth hormone, and still others claim to contain substances that increase the body's production of GH. There is no evidence that any of these products contain either a relevant product or a dose needed to induce the types of effects seen in studies. Over-the-counter and internet sales of these 'growth hormone' products are a major source of health fraud.

Certainly rHGH has shown benefits in treating wasting syndrome in advanced stages of HIV disease or AIDS, and its approval as a treatment for body lipodystrophy is encouraging. However, it's important that larger studies confirm these early findings. They can tell us whether or not increases in thymus size and CD4+ cell numbers, associated with rHGH use, ultimately benefit people living with HIV and result in better quality of life and longer life. Treatment with GH in HIV is encouraging and exciting, but far more research is still required.