If you have trouble reading this e-mail, you can see the online version at: www.thebody.com/topics.html
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The untold Side of the movie "Dallas Buyers Club"
The movie Dallas Buyers Club brings attention to a little-recognized part of the AIDS activist movement: ....
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Exhorbitant Price New Hepatitis C Drug
Fair Pricing Coalition Condemns Gilead Sciences on the High Price of New Hepatitis C Drug Sovaldi™...
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Six Promising HIV Drugs in the Pipeline (2013-2014)
What new HIV medications do we have to look forward to over the next few years? How will these newer drugs improve upon the older ones? To shed some light on these questions....
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What Can We Look Forward to in HIV Cure Research
TheBodyPRO.com's Nelson Vergel sat down with leading HIV cure research activist Richard Jefferys for an update on current important aspects, and controversies, in HIV cure research....
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What Supplements Can I take with HIV medications?
Is it ok to supplement with Creatine (Cell-Tech), and Protein (Nitro-Tech) along with Glutamine...
Tuesday, March 15, 2011
Fw: Hot Topics at The Body's "Ask the Experts" Forums
Saturday, March 12, 2011
How to Improve Finances Despite HIV
Wednesday, March 09, 2011
Dolutegravir, Trii and new abacavir data- How it all ties together
More on:
http://www.retroconference.org/2011/Abstracts/42541.htm
http://www.thebodypro.com/content/art60708.html
More on CROI:
http://www.thebody.com/content/art60501.html
Tuesday, March 08, 2011
Fw: Hot Topics at The Body's "Ask the Experts" Forums
If you have trouble reading this e-mail, you can see the online version at: www.thebody.com/topics.html
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Sunday, March 06, 2011
The Long-Term Survivor Dilemma
http://www.thebody.com/content/art60472.html?ts=pf
This sentence is part of a conversation that I seem to be having everywhere I go with my seminars -- one that manifests from a communal concern that many of us are sharing as we age as HIV long-term survivors.
A long-term survivor and activist friend of mine in San Francisco sat down with me for dinner and shared his fear of financial doom as he gets older with HIV. Like many of us, he left his career over 15 years ago due to HIV-related disability during years when we thought we had little ahead of us. As years went by, he became part of the large group of us who were committed full time to getting healthier again. Overcoming side effects, fatigue and other issues became a full-time job for years. Thoughts of replacing this full-time self-care job for a remunerated one never crossed our minds. Short-term goals were all we had for years.
With the advent of friendlier drugs and long-term virus suppression, many of us are confronted with a dilemma faced by few healthy people our age. Fear of financial doom in old age has replaced the fear of death that was part of our psyche for so many years.
Many people with HIV on permanent disability struggle by on less than $1,000 a month to pay all their bills. Others who get payments from private disability policies from their last job will lose them when they reach age 65. But who thought we were going to live to be 65 anyway!?
"Nelson, I am afraid to live to see my 80s and be a broke old man." "I would like to make money but am afraid of losing my disability and health care." "I am 57 and have a 16-year vacuum in my resume." "Who is going to hire me at this age, especially now in a recession, even if I tried to do what I used to before disability?" "If I did get a job, I am not sure if I can hold it with my frequent bouts of fatigue." "Is my fatigue related to not having a full-time job?" These sentences come from different mouths connected by a communal energy that is bursting to be expressed, but too ashamed to admit it.
As lucky survivors of a whole generation eroded by death, most of us are looking forward to a full life while searching for clarity and courage to regain financial security as we age with this disease.
In my PozHealth Yahoo group of over 3,200 people, most of us have lived with HIV for over 15 years and are aging with HIV. Some of us have only gotten to an undetectable viral load in the past three years. A few are still struggling with multidrug resistance. We often discuss obscure back- to-work programs that are scattered around the country. Some mention disability back-to-work programs like PASS or a trial work period to try to see if one can hold a job before getting out of disability. Most people's denial, confusion, inertia, fear of future health issues and/or just plain lack of trust in the system have been barriers to accessing these options. Some now stand on a cliff with a halting courage, poised to jump into the unknown.
Most of us have learned that a life purpose is key to health. Some of us have opted for reinventing ourselves without losing our benefits by being volunteer activists, writers, advisory board members at research sites, going back to school while strapped for cash, or doing cash-paying odd jobs for which many are overqualified. Most wonder how or if this work can lead to skill building or networking to ready us for the jump.
As we speak more about the science related to aging with HIV in conferences everywhere, the communal anxiety of surviving and aging with HIV is not addressed.
The social aspects of surviving HIV while living under national poverty income levels and with fragile medication access through financially troubled ADAP systems need to be addressed much like we address access to care and scientific research in HIV.
This is a great opportunity for large nonprofits that are now losing their funding. They may want to redirect their missions to empowering those of us who want to become part of a financially productive work force. Survivor training programs that coach people about their options while addressing their anxiety of the unknown are desperately needed.
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Zinc Fingers and Gene Therapies for HIV: Mimicking the Cured Berlin Patient?
Some HIV-infected patients who have an undetectable viral load while taking HIV medications continue to have low CD4+ cell counts. Lalezari et al decided to perform their proof-of-concept study on six of these patients: Each was on HIV antiretrovirals, had an undetectable HIV viral load, had a CD4+ cell count between 200 and 500, and had been HIV infected for more than 20 years. The patients were enrolled in one of two cohorts: in one, 10 billion total cells were modified; in the other, 20 billion. The process involved autologous (i.e., derived from the patient) R5-disrupted T cells that were expanded and modified with ZFNs outside the patients' bodies and then infused into the patients. The patients were followed weekly for one month and then monthly for 11 months post-infusion; blood and rectal mucosa samples were taken.
This novel study construction is the result of a history of groundbreaking findings. CCR5 has long been of interest to HIV researchers because many people who are resistant to HIV infection have a mutation in their CCR5 gene: the delta32 mutation. A minority of people of northern European descent (1% to 2.5%) have this mutation in the CCR5 receptor. After studying these patients, the oral CCR5 inhibitor drug maraviroc (MVC, Selzentry, Celsentri) was developed and ultimately approved in the U.S. in 2007. Fears that blocking the CCR5 receptor would lead to more rapid HIV disease progression or the emergence of other health problems have slowly dissipated since the drug was first given to humans in studies. (That said, there are some known adverse effects of CCR5 receptor blocking, including increased susceptibility to West Nile virus.)
As maraviroc was being developed, companies such as Sangamo BioSciences, Inc., were already trying to block the CCR5 receptor in a more permanent way: by using zinc finger nucleases, which act like scissors that cut the gene that codes for that receptor. But in the past, studies trying to modify CD4 cells in this manner have shown limited persistence of these cells after infusion in patients.
At the same time, some clinicians around the world were also trying to think outside the box on how to block HIV entry into CD4 cells. One such progressive thinker was Gero Hütter, M.D., from the Charité-Universitätsmedizin in Berlin. He had an HIV-infected patient with leukemia; he decided to try to treat both the patient's leukemia and HIV via a stem cell transplant using a donor with the delta32 mutation.
Hütter (and his patient) was lucky to find such a donor. The transplant -- which treats leukemia by essentially rebooting the body's immune system and creating new white blood cells -- also had the benefit of wiping out the HIV infection in the patient. The results of this extraordinary case were presented at CROI 2008 without receiving much excitement from the medical community.
It wasn't until almost two years later -- when it was found that the "Berlin patient" was still free of HIV not only in the blood, but in other compartments as well -- that excitement grew. Now, four years later, the patient remains HIV-free, which suggests he is cured of the disease. This has given companies such as Sangamo even more motivation to pursue a potential functional cure via disruption of the CCR5 receptor.
The data presented by Lalezari about Sangamo's ZFN approach showed several things:
- The infusion was safe and well tolerated.
- CD4+ cell count increases were seen in five of the six patients. The patient who did not respond had pre-existing antibodies to the adenovirus vector used to deliver the ZFN into the CD4 cell, so his body destroyed the vector, rendering the ZFN inactive. About 50% of the human population has those same antibodies, so a different vector may be used in future studies.
- The percentage of CCR5 disruption in the peripheral blood of the five responders was 6%, 3%, 1%, 2%, and 2% (respectively) at day 14 and persisted for the duration of the follow-up. CD4+ cell counts increased in all patients at day 14 (from an average of 35 to 1038 cells/mm3) and were sustained at all time points (with mean increases of 208, 86, 233, 911, 210 cells/mm3, respectively). CCR5-disrupted cells were detected in the rectal mucosa of all patients at all assessed time points, with levels of CCR5 disruption approximating that of peripheral blood when normalized for CD4 cells within each compartment.
- Three of the five responders had normalization of the CD4/CD8 ratio, which is a hallmark of the health of the immune system.
- There was a good uptake (grafting) of the modified CD4 cells into the blood of the five responders. In fact, by day 14 these patients had three times the quantity of cells that had been infused, showing that there was a growth of modified cells in their bodies. By day 90, the levels of persistent engraftment had become 6- to 40-fold greater than previously reported. After three months, 6% to 7% of the CD4 cells in the circulating blood had evidence of gene modification, which is over 10-fold higher than achieved by any previous T-cell modification therapy in HIV.
- Homing of these cells to the gut mucosa was observed in all patients tested, with CCR5 disruption levels similar to that of peripheral blood, suggesting these cells traffic normally. This is important since gut mucosa is the interface between the immune system and HIV.
- As I noted above, there were two cohorts in dosing: 10 and 20 billion cells. There seemed not to be a response difference between those two cell doses. Cells grafted and expanded during the first two weeks.
- What will happen long-term with the newly engrafted CD4 cells? Will they provide a survival or comorbidity benefit in these patients? (Note: Patients in this study will be followed for life.)
- Will this approach help control HIV replication in patients who stop antiretrovirals after long-term HIV suppression? How can we ethically ask patients to enroll in studies that require a structured treatment interruption? Will institutional review boards be willing to approve these kinds of studies in the future?
- Do people do better with more than one infusion? What is the best number of cells to ensure optimum immunological response?
- Will this approach help control HIV replication in treatment-naive patients who have a detectable viral load and who are not taking HIV antiretrovirals? Will these cells still have a survival advantage when challenged with untreated HIV? (Note: Lalezari is currently enrolling a 14-patient study in San Francisco that will attempt to answer these questions.)
- Will these gene-modified cells have a survival and activity advantage against HIV across the board? Will HIV viral load be controlled well enough for people to stop using antiretrovirals -- or, as stated in the question above, allow them to avoid antiretrovirals entirely?
- What will the cost of this procedure be?
- What happens to those with pre-exposure to the adenovirus vector who cannot respond to this type of zinc finger nuclease delivery method?
At a CROI 2011 press conference, Lalezari and other researchers involved in zinc finger nuclease and HIV gene therapy research discussed their findings and the broader implications of those findings. Click here to read that transcript.
Wednesday, March 02, 2011
The FDA says abacavir (Ziagen) does not cause cardiovascular problems, opening the door for GSK to combine it with their new integrase inhibitor for naive patients
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