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.

People with HIV with early-stage cancers are up to four times more likely to go untreated for cancer

People with HIV who are diagnosed with cancer are two to four times more likely to go untreated for their cancer compared to uninfected cancer patients, according to a new, large retrospective study from researchers in Penn Medicine's Abramson Cancer Center and the National Cancer Institute (NCI).

Life expectancy for HIV-infected people is now similar to uninfected people, but survival for HIV patients who develop cancer is not. While many studies have attempted to understand why HIV-infected cancer patients have worse outcomes, the new study, the largest of its size and scope, examined differences in cancer treatment as one potential explanation. For early-stage cancers that have the highest chance of cure with appropriate treatment, those with HIV were twice to four times as likely to not receive appropriate cancer treatment, the researchers found. HIV-infected people with lymphoma, lung cancer, prostate cancer, and colorectal cancer were almost twice as likely to be untreated for cancer, even after considering differences in age, gender, race, and stage.

"In my clinical experience, I have seen uncertainty surrounding treatment of HIV-infected cancer patients," said the study's lead author, Gita Suneja, MD, an adjunct assistant professor in the department of Radiation Oncology at the Perelman School of Medicine at the University of Pennsylvania and in the Abramson Cancer Center. "Patients with HIV have typically been excluded from clinical trials, and therefore oncologists do not know if the best available treatments are equally safe and effective in those with HIV. Many oncologists rely on guidelines based on such trials for treatment decision making, and in the absence of guidance, they may elect not to treat HIV-infected cancer patients due to concerns about adverse side effects or poor survival." "This could help explain in part why many HIV-positive cancer patients are not receiving appropriate cancer care," she added.

Dr. Suneja collaborated with researchers at the NCI, as well as registrars from three states -- Connecticut, Michigan, and Texas -- that provided data to NCI's HIV/AIDS Cancer Match Study. The researchers used the data to study adults diagnosed with non-Hodgkin lymphoma, Hodgkin lymphoma, or cervical, lung, anal, prostate, colorectal, or breast cancer from 1996 through 2010. Over 3,000 HIV-infected and one million uninfected cancer cases were examined.

The advent of antiretroviral therapy has changed the outlook in the fight against HIV/AIDS. People with HIV are living longer and healthier lives, and a disease that was once thought to be universally fatal has now become a chronic and manageable disease like diabetes or hypertension.

In the early era of the HIV epidemic there were reports of worse toxicity and side effects, but there are now more effective ways to support the immune system, most of them safe, tolerable and effective. Still, treatments for cancer patients with HIV can be clinically challenging due to drug interactions and the potential increase in immunosuppression from chemotherapy or radiation.

To help close the disparity gap among HIV positive patients with cancer and those not infected, cancer clinical trials should begin enrolling HIV-infected patients, the authors suggest, and cancer management guidelines should incorporate recommendations for HIV-infected patients.

"The results of this study are very concerning and require further investigation to understand why such a substantial proportion of HIV-infected cancer patients are not undergoing life-saving treatment," said Dr. Suneja. "As cancer becomes an increasingly common cause of death in the HIV population, the issue of cancer treatment in the HIV-infected cancer population will grow in importance."