Antiretroviral Therapy for HIV in First Four Months Is Crucial

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Photo: University of Texas Health Science Center/newswise.com
Sunil K. Ahuja, MD (centered) with his lab team in 2005.

Patients who are started on antiretroviral therapy for HIV-1 infection within four months of estimated infection date—and who have higher counts of CD4+ T-cells at the initiation of therapy—demonstrate a stronger recovery of CD4+ T-cell counts than patients in whom therapy is started later, a new study shows.

The report, published January 17 in The New England Journal of Medicine, is co-authored by physicians of UT Medicine, the clinical practice of the School of Medicine at The University of Texas Health Science Center (UTHSC), San Antonio, and the University of California, San Diego. Co-authors are from the University of California San Diego School of Medicine, the San Antonio Military Medical Center, and Monash University in Australia.

The study drew data from 468 patients followed in the San Diego Primary Infection Cohort. The study, funded by the National Institute of Allergy and Infectious Diseases (NIAID) and other sources, offers insight into the optimal timing of therapy.

“This study suggests greater urgency to start antiretroviral therapy earlier, when the most weapons in the immunity armamentarium are at the body’s disposal,” co-lead author Sunil K. Ahuja, MD, said. Dr. Ahuja is professor of medicine, microbiology/immunology and biochemistry in the School of Medicine at the UTHSC and director of the Veterans Administration Center for AIDS and HIV Infection, a national center within the South Texas Veterans Health Care System.

Observation of the transient restoration of CD4+ T-cell counts during the first four weeks of infection and their subsequent decline “raised the possibility that after acute infection there may be a narrow ‘restorative time window’ wherein the immune system could be strategically poised for recovery and that the likelihood and rate of recovery may be augmented by earlier initiation of potent antiretroviral therapy,” co-lead author Susan J. Little, MD, said. Dr. Little is professor of medicine at the University of California, San Diego School of Medicine.

Recovery of CD4+ T-cell counts to approximately normal levels of 900 or more cells per cubic milliliter was observed in 64 percent of participants who were put on antiretroviral therapy (ART) within four months of estimated date of infection, compared to 34 percent of participants in whom ART was initiated later.

“Even a fairly short deferral of ART after closure of this time window may come at the expense of compromised CD4+ T-cell recovery, irrespective of the CD4+ count at the time of treatment initiation,” Dr. Ahuja said. “Further studies are needed to determine whether starting ART within the restorative time window promotes strategies that help fully reconstitute the immune system.”

In an accompanying editorial, Bruce Walker, MD, and Martin Hirsch, MD, of Harvard Medical School wrote: “The question of when to initiate ART remains a difficult one, particularly in resource-limited settings, but the studies in this issue of the Journal provide strong supportive evidence suggesting a benefit for early therapy.” The authors noted that the study relies on a surrogate measure of disease progression, CD4+ T-cell count, rather than on clinical outcomes.

“Future studies of treatment even earlier in the course of infection may show additional benefits, and a population of such patients will be an important study group for eventual studies aimed at ‘cure’ of infection,” Walker and Hirsch wrote.

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Stopping Smoking Reduces Risk of Bacterial Pneumonia

Bacterial pneumonia is one of the most common serious  infections occurring in people living with HIV. ScienceDaily reports that a metanalysis of cohort and case control  studies published in BioMed Central’s open access journal BMC Medicine finds that current smokers with HIV were at double the  risk of bacterial pneumonia than non-smoking counterparts, but that when people  stopped smoking their risk was reduced.

The metanalysis re-analyzed the data of several thousand  participants with HIV, from 14 studies based in the USA,  Europe, and South Africa.  Overall, it appeared that current smoking was associated with a 70-100%  increase in risk of bacterial pneumonia, compared to non-smokers, but that  stopping smoking decreased this by about a third. This was independent of CD4  count or antiretroviral therapy.

Professor Paul Aveyard, from the University of Oxford  and leader of the study, explained that, “Antiretroviral treatment means that  people with HIV can have a normal life expectancy. However, they still have  substantially increased health risks compared to the general population,  including risk of pneumonia. Our results show that smokers with HIV have twice  the risk of bacterial pneumonia, but that stopping smoking can reduce this  risk. In order to prevent this potentially life threatening lung disease we  believe that smoking cessation programs should be promoted as part of HIV  treatment.”

Neuropathy and HIV: A Progress Report

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Friday, 09 November 2012 Author //  Dave R Categories //  Health, Treatment, Living with HIV, Dave R

Dave R writes…Neuropathy affects up to 40% of all people with HIV, yet the treatment has remained more or less the same for decades. Prescribing drugs meant for other diseases, has led to haphazard results; time for a change – but is it happening?

Neuropathy and HIV: A Progress Report

Couple the conditions neuropathy and HIV-infection together and in 2012, you have more people than ever who understand what you’re talking about. Growing older and surviving with HIV seems to mean the increase of long-term, age or HIV-related, side-effect conditions like neuropathy. To save time in relation to this article; much more information about the disease and its links to HIV can be found in other articles.

It’s an infuriating and frustrating problem for both patients and doctors. Neuropathy is one of those diseases where the mainline, standard treatments seem to have remained static for the last thirty years or more. Occasionally, a different anticonvulsant is tried out, or a combination of antidepressant and anticonvulsant, analgesic, or opiate but this comes more from a feeling of hopefulness than conviction and good science on the part of doctors. In general, people who unfortunately end up with neuropathy from whatever cause (and there are over a hundred!) follow the same medication routes that have been used since the 60’s, until hopefully something works. It really is a sticking a wet finger in the wind sort of medical approach. The downside is that many people are never prescribed anything that really works for them and the symptoms can gradually worsen. In the end, the only pain-killing options are opioids, with all their attendant side effects and addiction potential. Little wonder that all involved tear their hair out with frustration. Medicine isn’t meant to be this way in the 21th Century; even HIV sees progression with its medications!

That’s probably why so many people turn to alternative therapies and supplements to try anything that might relieve the problems. In that sense, different supplements and therapies spring up every year like mushrooms in a field. Some end up being tested and approved and genuinely help people but many are pretty much worthless and a waste of money. That’s the biggest problem with neuropathy; it creates desperation and the need to clutch at straws. Yet the problem is largely unrecognised by the population at large, despite there being 20 million Americans alone who suffer from various forms of nerve damage. To be clear, only certain types of neuropathy can be reversed and even then, only when they are discovered very early in the disease – generally it’s something with you for the long haul.

Over the last decades, it has been a doom and gloom scenario for many people, as they work their way through drugs meant for other diseases in the hope that they will eventually get some relief from their neuropathic symptoms.

However, that very increase in numbers of people suffering serious nerve damage has sparked a wave of studies in the research world and glimmers of hope for sufferers. Unfortunately people living with HIV can’t take any of the credit; if it were just our little demographic, a cynic might suggest that new research wouldn’t be so forthcoming. Luckily for us (but not if you also have diabetes), it is the explosion in diabetes cases that is driving the need for effective treatments for neuropathy. The burgeoning disease of diabetes is the single largest cause of nerve damage, especially in the burger and sugar-guzzling West. That becomes a drain on health budgets and services; ergo a new enthusiasm in the research labs.

The outlook for neuropathy patients may not be quite as gloomy as it once was then and this article will bring you up to date with some of the more recent developments within the scientific and medical world. Be warned though, these will probably not result in ‘cures’ or even off-the-shelf medications in the very near future but do show that the pharmaceutical industry seems to be finally waking up to the fact that this is a huge problem across the entire spectrum of society. Significant progress seems to have been made even during the last year. As you know, drug companies are not known for their philanthropic motives but there’s a vast amount of money to be made as soon as effective treatments can be developed and that, plus pressure from health regulators to deal with diabetes, will unfortunately, probably be the driving force behind finding new treatments. That said; do we care how they get there? Not if we have neuropathy we don’t! Whatever the motives, we’re going to love the pharmaceutical company that brings us genuine relief from nerve damage.

Recent Developments in Research

The following are some of the many recent developments in understanding of how, what and why nerves are damaged and what can be done to alleviate the results.

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First, a step backwards but an important one for many people currently being prescribed the anticonvulsant Lyrica (pregabalin) for neuropathy. For those who haven’t already heard, in May 2012 Lyrica (Pregabalin) was dropped as a treatment for diabetic and HIV-related neuropathy by none other than its makers, Pfizer. It proved to be ineffectual in treating neuropathy from those causes. Despite this, doctors all over the world are still prescribing it because they either haven’t heard, or because it’s on the standard list, or they have always prescribed it and have a number of patients for whom it seems to have worked. The fact is that the majority of people have found no improvement from taking Lyrica (pregabalin) and what’s more have suffered more from the side effects than from the neuropathy itself. It may be worth discussing this with your specialist if that’s the case for you. For Pfizer to withdraw support for their own drug is hugely significant – no drug company cuts the throat of its own cash cow for no reason!

By far the largest area of research is at molecular and cellular level which may leave most people scratching their heads and reluctant to read on. However, scientists in both universities and the pharmaceutical company research departments seem to have recently invested a great deal more time in looking at nerve cells, why they are damaged and what processes both chemical and physical cause so much pain and discomfort for neuropathy patients. Of course, this sort of research has undoubtedly been going on for years but with discouraging results, (otherwise new treatments would have been available long before now). The technology must also have improved to the point where more detailed and specific research is now possible. Published scientific findings also stimulate both new research and competition, so exciting results in one university or research lab tend to encourage others to top them with results of their own. More money for research may also be available, as political decisions outside the pharmaceutical industry influence progress. Administrations everywhere are realising the huge costs associated with ‘life-style’ illnesses like, diabetes, cancer, HIV and others. They also realise that continuing to pour money into paying for ineffective treatments with side effects just prolongs the process and increases costs exponentially. The pharmaceutical companies may finally be facing pressure from politicians but they are also beginning to realise the vast profits to be made from finding the ‘mother lode’ of nerve damage treatments. They can no longer really justify making profits from and using up reserves of drugs used for other medical conditions, when they have such a hit and miss effect on neuropathy patients. Sheer numbers and potential profits, then, are driving the search for new drug treatments.

So is it possible to describe some of the developments in molecular and cellular research for nerve damage? I’ll give it a go and have to confess my own understanding is about as shallow as most people’s but we need to have an idea of what sort of treatments are going to affect our futures with this disease. If nothing else, it helps us to understand exactly how complex the whole problem is.

The first is new research that has identified precisely which cells and which sub-sets of cells, are responsible for long-term nerve pain. See an explanation.

Then studies have identified the cells (Schwann cells) which protect the myelin sheath which is the insulation layer around nerves (to give you an idea, a myelin sheath is like the plastic around electricity wires – you get a short circuit if that is damaged too). More information about this research.

Further research has identified the importance of something called metabolomics. This looks at why nerve pain persists for so long and why many medications have no effect. The clue lies in a by product of cellular membranes called DMS which seems to be present in large amounts in the spinal cords of lab rats and mice with neuropathy. They are working on finding ways of inhibiting this DMS and thus relieving long-term pain.

Similarly, American researchers have discovered a group of drug molecules which are found naturally in the body and stabilise other molecules, in order to block neuropathic pain. The idea is that these selective molecules inhibit a key enzyme called soluble epoxide hydrolase. Blocking this enzyme successfully blocks pain sensations. This then has implications for developing new drug treatments which will work much better on neuropathic symptoms. The problem is that the research is still in a very early stage.

Another research study aims to block nerve pain signals by using glycene. Glycene is an amino acid which is known as an inhibitory neurotransmitter. It works at the junction between two nerves, known as the synapse and halts the transmission of pain signals along those nerves to the brain. However, glycene quickly dissipates in these places and some have recommended taking supplements to encourage the body to create more naturally. This study questions the efficiency of that but points out that glycene is one of the very promising natural products of the body which needs and is getting much more research. More information here.

Yet another research study has discovered that a certain protein (LRP4) has to be present on the surface of both muscles and in the brain in order to regulate muscle function. If this isn’t the case, several conditions including neuropathy can occur. Many neuropathy patients discover that their muscles stop working efficiently and lose strength after time – the lack of this protein LRP4 in both muscle cells and neurons leads to communication breakdown, which as we all know leads to the numbness, tingling and pain which often appear with nerve damage. Finding a way to either maintain protein levels or introducing it externally may well help reduce the problem. More information here.

Another project has looked into how the brain stores memories of pain and why for instance, phantom limb pain occurs (when a limb is lost, people still feel the pain as if it’s still there). Again, it concerns a type of protein (PKMzeta) which builds and maintains memory by strengthening the connections between neurons. Scientists think that if they can block the activity of PKMzeta, they can reduce the hypersensitivity that causes nerve pain and they’re well on their way to finding something that will do just that. Again, a work in progress we have to say but the future looks a little more hopeful. Read more here.

Finally in this group of studies, the possibilities of nerve transplantation are being explored, in cases where nerves are damaged. This means basically transplanting immature neurons in the hope that they will grow into full nerve cells. During the studies small fractions of the transplanted cells survived and matured into functioning neurons. The cells then integrated into the nerve circuitry of the spinal cord, forming synapses and signalling pathways with neighbouring neurons. Most importantly, as a result, pain hypersensitivity associated with nerve injury was almost completely eliminated. Whether health authorities will be able to cope with the expense of this sort of transplant treatment is the question but there’s little doubt, it sounds promising! More information here.

You can see from these few examples that many people and research labs are busy working at the most basic level of nerve behaviour to find where, why and how, molecular and cellular activity cause such unpleasant neuropathic symptoms. Genetic research is another fast-growing sector, largely due to the huge advancements in techniques in that area and eventually, altered or modified DNA may provide permanent answers. It is slow work though and we have to hope that sooner rather than later a significant breakthrough will be made. Hoping that just one of the studies above may lead to real treatment progress, gives room for optimism.

Researching Nature

Research is not only being done at microscopic levels within the body but studies are also being done in nature to see if there is anything in the animal and plant kingdoms which may help. This has produced some strange studies and conclusions.

  • A certain sea-snail saliva for instance could be a replacement for morphine in the future.
  • Taiwanese scientists have discovered a compound derived from certain corals called Capnellene. This may also work on certain cells (microglia) and significantly reduce neuropathic pain.
  • Scorpion, spider and snake venoms may also provide answers to controlling nerve pain. These venoms work on the sodium channels in the nervous systems of mammals, so it seems logical that controlled doses may help with neuropathic symptoms.
  • Turmeric (also known as Curcumin, Curcuma) which is used widely in cooking, is one of the new buzz words for helping with all sorts of problems including neuropathic pain. Every now and then, a natural remedy emerges that catches on in the market; sometimes with merit and sometimes not. However, one of the most promising is Turmeric or Curcumin, a root used widely in Asian cuisine, generally in powder form. It’s cheap and maybe worth a try – some people swear by it but do your own research.

Of course the best known natural remedy used to help with neuropathic problems is cannabis. The hysterical reactions to cannabis for medical purposes are much more to do with politics and ‘the war on drugs’ than the medical benefits it can undoubtedly bring for many people. It’s one of the very few recognised effective remedies for neuropathic pain but a) you have to be aware of the laws in your area, b) you have to be able to smoke it (with all its associated lung dangers) and c) you have to be able to cope with getting high (mildly or otherwise). For those reasons many people can’t take advantage of cannabinoids. However, there has been a new synthetic version of THC (the principle working element of cannabis) created by the University of Calgary and this could prove to be a godsend for many neuropathy sufferers because smoking will be removed from the equation. It is far more likely to be accepted by law agencies because it can then be issued on prescription. However, like most developments, we’re not there yet.

Other approaches

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There are many more studies and investigations of potential natural remedies, from many different natural sources taking place. If only a handful end up being successful and effective and available to our doctors, or on the shelves of our health food shops, it could relieve suffering for millions.

It seems that no stone is being left unturned in the search for answers and that includes looking at other cultures and other medical practices. Acupuncture and acupressure have been tried by many neuropathy patients over the years, with varying levels of success. Like everything else at the moment, it works for some but not for others. However, new research has discovered that much longer-lasting effects can be achieved by so-called PAP injections (prostatic acid phosphatase) using the same pressure points used for centuries in acupuncture. This so-called PAPupuncture therapy has been proved (in the lab) to extend pain relief much further than with normal acupuncture methods and may well be a useful therapy in the future, for those who don’t wish to increase their drug consumption.

Finally in this section, it may seem that the world is turned on its head but a modified version of the herpes virus is thought to theoretically work on peripheral nerves, so that pain can be directly reduced in those areas. A scary thought perhaps, if you’re to be injected with herpes but perhaps logical if you think that Shingles is also a form of neuropathy and is caused by a herpes virus. Anyone suffering from Shingles, knows what nerve pain can do!

Lastly, apart from the searches for new medications and treatments, which are very difficult for the layman to understand, scientists are also trying to develop better versions of current drug treatments. We know about the random success/failure rate of antidepressants and anticonvulsants and it is likely that there isn’t much progress to be made in those drug areas. We also know about the last resorts in the opioid family. Effective pain killers but often strongly addictive and loaded with side effects, they are unfortunately a question of necessity for many neuropathy patients.

Scientists are discovering that opioids are a group of drugs with more possibilities and their effectiveness is probably more easily adapted and manipulated. Consequently, new opioids and members of the opioid/morphine family are coming on to the market. Tapentadol,(Nucynta in the USA and Palexia in Europe) for instance, is newly approved in the States and can be equated to Tramadol but works slightly differently, more effectively and with less side effects. It will be a welcome alternative for many people.

Researchers are also looking for ways to prolong the pain-killing effects of morphines and opioids, thus reducing the need for higher doses and reducing addiction dangers. They have found that Resveratrol, (naturally found in red wine) can preserve the effects of morphine in rats – most importantly, in rats that have developed morphine tolerance. In humans, morphine tolerance creates a need for higher doses to achieve the same effect so discovering something that delays tolerance, or maintains the pain killing effects, is clearly of great value.

Conclusion

If you’ve got this far, you’re probably reeling from information-overload but the intention is to reassure you that serious efforts are being made to find solutions for both nerve damage and the uncomfortable results of that for millions of people. Eventually, a few will make it through the rigorous processes and end up as viable options for our doctors to prescribe. Unfortunately, it takes time and that’s difficult to swallow for a patient in extreme pain or discomfort. You’re already on drugs for your neuropathy; they may be working or not, or just partly. All you want is something to take the problem away and preferably a one-drug-cures-all type of treatment. The truth is that that’s not going to happen in the very near future but it will eventually happen. Finally, health authorities and pharmaceutical companies are getting their acts together and working for us instead of palming us off with dangerous drugs meant for other diseases.

Money will play a part in the speed of progress and research finance is often the first to go in times of financial crisis, along with the willingness of health authorities and insurance companies to pay for expensive new drugs but the picture is brighter than ten years ago. All concerned are realising that neuropathic pain is a far greater problem than they ever imagined and the increase of the diseases that cause it (along with people living longer) is only going to make that bigger. Something has to be done to reduce the costs of long term treatment and that means finding things that genuinely work. Lab rats and mice may view this with horror but for many people with neuropathy, it just can’t come soon enough!

Support Group Meeting @ MIRC – 2013

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Fewer black women are being infected with HIV

Created on 14 January 2013 Written by Vitals Category:

ATLANTA – Fewer black women in the United States are being infected with HIV, but the number of young gay and bisexual men infected is rising, the Centers for Disease Control and Prevention said on Wednesday.

Between 2008 and 2010, the number of newly infected black women dropped 21 percent, according to the CDC report. Yet despite the decline, they still accounted for 70 percent of all new HIV cases among women, the federal health agency said.

The rate of new infections for black women was 20 times higher than the rate for white women, the CDC said.

The number of new infections among young gay and bisexual men increased by 22 percent during that same two-year period, the CDC said.

The number of new HIV infections diagnosed annually in the overall U.S. population remained unchanged between 2008 and 2010 at about 47,500, according to health officials.

Public information campaigns on HIV prevention and testing seem to be working in lowering the number of new infections among African-American women, said Joseph Prejean, chief of the Behavioral and Clinical Surveillance Branch in the CDC’s division of HIV/AIDS Prevention in Atlanta.

“We are encouraged to see some declines among African-American women,” Prejean told Reuters. “They’ve been one of the most severely affected populations. We’re cautiously optimistic that this could be part of a longer-term trend.”

Among young gay and bisexual men, efforts to fight HIV have not been as effective, possibly because of advances in treatment for AIDS, the immune disorder caused by HIV, Prejean said.

PFAG Founder Dies at 92

Jeanne Manford, the founder of PFLAG (Parents, Families and Friends of Lesbians and Gays) and one of the first straight allies in the LGBT rights movement, has died at the age of 92.

The Huffington Post reported on January 8 that Manford died at her Daly City, California home after being in declining health for some time.

In 2009, President Obama described Manford’s work at a Human Rights Campaign dinner, saying, “That’s the story of America: of ordinary citizens organizing, agitating, and advocating for change; of hope stronger than hate; of love more powerful than any insult or injury; of Americans fighting to build for themselves and their families a nation in which no one is a second-class citizen, in which no one is denied their basic rights, in which all of us are free to live and love as we see fit.”

Manford became an LGBT rights activist in 1972 after her son Morty was beaten during a Gay Activists Alliance demonstration. After the attack, Manford wrote a letter to the editor of the New York Post declaring, “I have a homosexual son and I love him.”

She and Morty marched together in the 1972 Christopher Street Liberation Day Parade (predecessor to NYC’s LGBT Pride Parade) carrying a placard saying “Parents of Gays: Unite in Support of Our Children.” Inspired by the enthusiastically positive reaction they got, they developed the concept of an organization of the parents of gays and lesbians that Manford later said could be, “a bridge between the gay community and the heterosexual community.” The first meeting of PFLAG (then known as “Parents of Gays” or POG) was held in New York’s Metropolitan Community Church a year later, with her husband participating as well.

A private interment service will be held and details of a celebration of Manford’s life and legacy will be announced later. The family requests that any donations be made to the Jeanne Manford Legacy Fund to support the ongoing work of PFLAG National: 1828 L Street, NW, Suite 660, Washington, D.C. 20036.

Link between pot smoking and IQ drop challenged

NEW YORK — A new analysis is challenging a report that suggests regular marijuana smoking during the teen years can lead to a long-term drop in IQ. The analysis says the statistical analysis behind that conclusion is flawed.

The original study, reported last August, included more than 1,000 people who’d been born in the town of Dunedin, New Zealand. Their IQ was tested at ages 13 and 38, and they were asked about marijuana use periodically between those ages.

Researchers at Duke University and elsewhere found that participants who’d reported becoming dependent on pot by age 18 showed a drop in IQ score between ages 13 and 38. The findings suggest pot is harmful to the adolescent brain, the researchers said.

Not so fast, says an analysis published online Monday by the Proceedings of the National Academy of Sciences.

Ole Rogeberg of the Ragnar Frisch Center for Economic Research in Oslo, says the IQ trend might have nothing to do with pot. Rather, it may have emerged from differences among the study participants in socioeconomic status, or SES, which involves factors like income, education and occupation, he says.

He based his paper on a computer simulation. It traced what would happen to IQ scores over time if they were affected by differences in SES in ways suggested by other research, but not by smoking marijuana. He found patterns that looked just like what the Duke study found.

In an interview, Rogeberg said he’s not claiming that his alternative explanation is definitely right, just that the methods and evidence in the original study aren’t enough to rule it out. He suggested further analyses the researchers could do.

The Duke scientists, who learned of Rogeberg’s analysis late last week, say they conducted new statistical tests to assess his proposed explanation. Their verdict: It’s wrong. Rogeberg says they need to do still more work to truly rule it out.

Experts unconnected to the two papers said the Rogeberg paper doesn’t overturn the original study. It “raises some interesting points and possibilities,” but provides “speculation” rather than new data based on real people, said Dr. Duncan Clark, who studies alcohol and drug use in adolescents at the University of Pittsburgh.

Dr. Nora Volkow, director of the National Institute on Drug Abuse, said observational studies of people like the Duke work can’t definitively demonstrate that marijuana cause irreversible effects on the brain. In an email, she said Rogeberg’s paper “looks sound” but doesn’t prove that his alternative