Johns Hopkins study suggests the commonly prescribed anti-retroviral drug efavirenz attacks brain cells

Popular HIV drug may cause memory declines

Johns Hopkins study
suggests the commonly prescribed anti-retroviral drug efavirenz attacks brain
cells

The way the body metabolizes a commonly prescribed anti-retroviral
drug that is used long term by patients infected with HIV may contribute to
cognitive impairment by damaging nerve cells, a new Johns Hopkins research
suggests.
Nearly 50 percent of people infected with HIV will eventually
develop some form of brain damage that, while mild, can affect the ability to
drive, work or participate in many daily activities. It has long been assumed
that the disease was causing the damage, but Hopkins researchers say the drug
efavirenz may play a key role.
People infected with HIV typically take a cocktail of medications
to suppress the virus, and many will take the drugs for decades. Efavirenz is
known to be very good at controlling the virus and is one of the few that
crosses the blood-brain barrier and can target potential reservoirs of virus in
the brain. Doctors have long believed that it might be possible to alleviate
cognitive impairment associated with HIV by getting more drugs into the brain,
but researchers say more caution is needed because there may be long-term
effects of these drugs on the brain.
“People with HIV infections can’t stop taking anti-retroviral
drugs. We know what happens then and it’s not good,” says Norman J.
Haughey, Ph.D., an associate professor of neurology at the Johns Hopkins
University School of Medicine. “But we need to be very careful about the
types of anti-retrovirals we prescribe, and take a closer look at their
long-term effects. Drug toxicities could be a major contributing factor to
cognitive impairment in patients with HIV.”
For the study led by Haughey and described online in the Journal of Pharmacology and Experimental Therapeutics,
researchers obtained samples of blood and cerebrospinal fluid from HIV-infected
subjects enrolled in the NorthEastern AIDS Dementia study who were taking
efavirenz. Researchers looked for levels of the drug and its various
metabolites, which are substances created when efavirenz is broken down by the
liver. Performing experiments on neurons cultured in the lab, the investigators
examined the effects of 8-hydroxyefavirenz and other metabolites and found
major structural changes when using low levels of 8-hydroxyefavirenz, including
the loss of the important spines of the cells.
Haughey and his colleagues found that 8-hydroxyefavirenz is 10
times more toxic to brain cells than the drug itself and, even in low
concentrations, causes damage to the dendritic spines of neurons. The dendritic
spine is the information processing point of a neuron, where synapses — the
structures that allow communication among brain cells — are located.
In the case of efavirenz, a minor modification in the drug’s
structure may be able block its toxic effects but not alter its ability to
suppress the virus. Namandje N. Bumpus, Ph.D., one of the study’s other
authors, has found a way to mod
ify the drug to prevent it from metabolizing
into 8-hydroxyefavirenz while maintaining its effectiveness as a tool to
suppress the HIV virus.
“Finding and stating a problem is one thing, but it’s another
to be able to say we have found this problem and here is an easy fix,”
Haughey says.
Haughey says studies like his serve as a reminder that while
people infected with HIV are living longer than they were 20 years ago, there
are significant problems associated with the drugs used to treat the infection.
“Some people do seem to have this attitude that HIV is no
longer a death sentence,” he says. “But even with anti-retroviral
treatments, people infected with HIV have shortened lifespans and the chance of
cognitive decline is high. It’s nothing you should treat lightly.”
###
The study was supported by grants from the National Institute on
Alcohol Abuse and Alcoholism (AA0017408), the National Institute of Mental
Health (MH077543, MH075673 and MH71150), the National Institute on Aging
(AG034849) and the National Institute of Neurological Disorders and Stroke
(NS049465).
Other Hopkins researchers involved in the study include Luis B.
Tovar y Romo, Ph.D.; Lindsay B. Avery, Ph.D.; Ned Sacktor, M.D.; and Justin
McArthur, M.B.B.S., M.P.H.

NOVEL APPROACHES TO CURING HIV

One of the greatest advances in modern medicine has been the development of HAART for the treatment of HIV. HAART decreases HIV-associated morbidity and mortality for patients with regular access to these medications, but it does not appear to completely restore their health for reasons that currently are unclear. As a result, there has been an increased interest in ways to fully eradicate HIV from infected individuals (ie, a “sterilizing cure”), or to at least achieve a “functional cure.”

Click Here To Download the Paper

Fw: News & Views: “Premature Aging” — Myth vs. Reality; HIV Pregnancy Tips; Transmission Sentence Overturned; and More

From: “News at The Body” <update@news.thebody.com>
Date: 27 Sep 2012 15:24:31 -0400
To: <nelsonvergel@yahoo.com>
ReplyTo: “News at The Body” <update@news.thebody.com>
Subject: News & Views: “Premature Aging” — Myth vs. Reality; HIV Pregnancy Tips; Transmission Sentence Overturned; and More

If you have trouble reading this e-mail, you can see the online version at: www.thebody.com/updates.html

September 27, 2012 Top Stories at TheBody.com News & Views Library Change/Update Subscription


BLOG CENTRAL Alive2 Alive2: Don’t Think You Can’t Learn More About HIV

“When I came to [TheBody.com] I wasn’t as knowledgeable about much of anything involving HIV/AIDS; I wasn’t sure what the numbers meant, much less how they affected my health. … After days turned into months, I began to start to know enough information to become my own best advocate.”

Aaron Laxton Aaron Laxton: Vote or Die (Video)
“As much as activists get noticed, there is something that every person can do that has the potential of changing society: voting! I encourage all of my viewers to register to vote and, on Nov. 6, 2012, to let your voice be heard.”

Rae Lewis-Thornton Rae Lewis-Thornton: Surrendering to Self-Care (Video)
“Even Jesus took time to renew. Self-care does not mean that you are weak, it just means that you are trying to be the best that you can be. Take the time that you need to be your best! I give you permission.”

Reggie Smith Reggie Smith: Having Children, and the Way of the World
“Having something to look forward to, like children, has had a very positive and healing effect on my life. … Having HIV should not deprive anyone of having the experience of parenthood.”

More Headlines From HIV/AIDS Blog Central:

Join the Conversation “Michael (From Los Angeles) on “Police Video Prompts Allegations of HIV Discrimination

“Maybe he should have disclosed to the HIV-positive woman that he is stupid first. Isn’t that something she should know before dealing with him, to spare her the harassment she encountered because of his stupidity?”

Read the rest of this comment and join the discussion on this article!

HIV TREATMENT & HEALTH ISSUES gnome “Premature Aging” and HIV: Dispelling Myths and Calculating Risk

Here’s the bottom line on “accelerated aging” among people with HIV: It’s probably not as bad as you think. New research is rewriting much of what we thought we knew about aging and HIV.

question marks Frequently Asked Questions About HIV & Pregnancy
Are you concerned about getting pregnant in the presence of HIV — from planning to conceive safely to choices around testing and treatment for your newborn? TheBody.com’s experts have answered just about every pregnancy-related question under the sun.

Stribild Stribild (a.k.a. “Quad”) May Slightly Outperform Other Popular First-Line Options, Study Finds
The newly approved four-in-one drug Stribild stands up against both Atripla and a regimen comprised of Norvir, Reyataz and Truvada, according to combined results from three 48-week studies.

TheBodyPRO.com Ongoing HIV Infection Could Explain Low CD4 Counts Despite Undetectable Viral Loads, Study Suggests
Even if people start HIV treatment late, they still have a good chance at recovery. However, not everyone benefits equally: For instance, some people seem to have poor CD4 count gains even when HIV meds are working well. New research explores why.

Rae Lewis-Thornton A Diva Talks About 25 Years on HIV Meds (Video)
Rae Lewis-Thornton’s list of past treatment regimens reads like a history of HIV drug development — because it is. She shares her experiences with “all the nucleosides” — starting with Retrovir, the first HIV drug — and the mixed blessing of hope and crippling side effects that was the earliest protease inhibitors.

More Headlines on HIV Treatment & Health Issues:

need a friendly reminder?
alarm clock Hey, nobody’s perfect. We can all use a little nudge sometimes to help us remember our HIV meds, upcoming doctor’s appointments, prescription refills and other tasks. Use TheBody.com’s new free, private Personal Reminder Service to:

  • Receive a text message, email or voice mail when it’s time for a medication dose.
  • Receive reminders before upcoming doctor’s appointments.
  • Set up online prescription refills and deliveries via mail.
  • And much more!

  • HIV NEWS & POLICY gavel Minnesota Appeals Court Reverses Conviction in HIV Transmission Case

    The Minnesota Court of Appeals has reversed the conviction of an HIV-positive man who was accused of passing the virus to another man through unprotected sex. The court ruled that the statute under which the man was tried was ambiguous.

    Virginia How Virginia Kept the Pills Coming to ADAP Clients on Its Waiting List
    “No one enjoyed the ADAP [AIDS Drug Assistance Program] waiting list experience, but sometimes adversity produces remarkable things,” the National Association of People With AIDS reports. They interviewed the head of Virginia’s ADAP to find out how he kept the HIV meds flowing even after funding had dried up.

    More HIV News & Policy Headlines:

    Visual AIDS: Art from HIV-Positive Artists
    Image from the September 2012 Visual AIDS gallery Detail from:
    “Hello From Bertha Still,” 1984
    Mark Morrisroe

    Visit the September 2012 Visual AIDS Web Gallery to view our latest collection of art by HIV-positive artists! This month’s gallery, "Elegy for a Queendom That Never Became," is curated by Quito Ziegler.


    OPINIONS & PERSPECTIVES 4 interviewees Word on the Street: What Did You Expect While You Were Expecting?

    When you’re an HIV-positive mom-to-be, there’s no such thing as having “too much” information. We asked a bunch of moms who’ve been there: What do you know now about having a baby while HIV positive that you wish you’d known at the time you were pregnant?

    4 interviewees The Golden Girls (and Boys): What It’s Really Like to Grow Older With HIV/AIDS
    We invited four people over 50 who are living with HIV to sit down and talk to each other about their lives, the challenges they face and the successes they have achieved over the years.

    Jeffrey Keller All Jeff Keller Wants Is a Little Respect for People With HIV
    Jeffrey Keller writes and teaches about HIV, and has made valuable contributions to the AIDS movement. He is the kind of lawyer — and man — who fights against injustice at every turn. If his work doesn’t tell you that, then the “Respect Everyone” tattoo on his inner right forearm will.

    More Opinions & Perspectives:

    spotlight series: pregnancy & hiv
    Navigating the joys and challenges of having babies while living with HIV can be daunting. But many families have done it before, as have many health providers. Check out TheBody.com’s Spotlight Series on Pregnancy & HIV for information, stories and advice that we hope will help you on your journey.

    pregnancy & HIV/AIDSLet’s Talk About Having Babies — Before and After HIV/AIDS
    What’s it like being pregnant and living with HIV? Four HIV-positive moms from different parts of the United States chat about their experiences.

    Caring for HIV-Negative Kids (and Yourself) in an “HIV Family”
    What happens after your baby is born? Our four HIV-positive moms discuss this vital issue.

    Teniecka’s Pregnancy Journal, Entry #1: Expecting Number Four!
    Follow along as blogger Teniecka Drake recounts her fourth pregnancy while living with HIV, and as she and her family prepare for the new arrival.


    HIV/STD TRANSMISSION & EDUCATION HIV cell From Exposure to Infection: The Biology of HIV Transmission

    One way HIV is transmitted is through sex — and the journey begins with exposure. Join James Wilton of the Canadian AIDS Treatment Information Exchange as he demystifies the journey that HIV takes from the time someone is first exposed through the effects that infection have on a person’s immune system.

    OaraSure Test OraQuick In-Home Rapid HIV Test Available for Purchase Online
    The OraQuick over-the-counter, in-home rapid HIV test, which was approved in the U.S. earlier this year, has recently become available for purchase online at a cost of $39.99.

    More Headlines on HIV/STD Transmission & Education:


    Worried Your Spam Filter Might Trash Our Mailings? TheBody.com’s e-mail updates are especially prone to being caught up in spam filters, since our newsletters tend to refer frequently to sex, drugs, the human anatomy and so forth.

    To make sure you never miss one of our mailings because anti-spam software labeled it as junk mail, add update@news.thebody.com to your address book, talk to the person who manages your e-mail security or check your anti-spam program’s instructions for more information. About This E-mail This e-mail update has been sent to nelsonvergel@yahoo.com.

    Want to change your subscription? Click here or send us a message at updates@thebody.com.

    Missed an update? Our archive of past updates will keep you in the loop.

    Have any other questions or comments, and don’t want to send an e-mail? Feel free to snail-mail us at:

    TheBody.com’s E-Mail Updates
    Remedy Health Media, LLC
    250 West 57th Street
    New York, NY 10107

    Advertisement Advertisement

    Follow Us
    Facebook  Twitter
    Activist Central
     Movie Event: Celebrate Our History and Build Our Movement

     Call for Abstracts for the 2013 National Af-Am MSM Leadership Conference in L.A.

     Tell Your Representative to Support Cure for AIDS Act!

     Train and Triumph With Team to End AIDS!

     Under Attack: Your Health Care Rights

    HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms?

    I am convinced that our mitochondria are affected even after years off Zerit, DDI or AZT. Mitochondrial dysfunction has been widely reported with D drugs (D4T, DDI) and AZT and has been linked to lipoatrophy and metabolic problems.  But I think what we ignore is the permanent effects on the mitochondria even after years of stopping those drugs. 

     Although mitochondria DNA in fat and muscle cells gets better after switching from Zerit or AZT to tenofovir (the most widely used nucleoside analog used in HIV), it never returns to normal (compared to healthy controls).  HIV in itself is known to affect mitochondria function.

    Can fatigue get better by improving mitochondrial function with supplementation? We do not have much data on this. In fact, fatigue related research in HIV is almost non existent.  Except for researchers like Dr Judith Rabkin in NY, almost no one is looking at this problem commonly reported in clinical studies of new HIV drugs. Fatigue is one of the top quality of life issues reported by most HIV long term survivors and even in those with early disease.

    Note: Fatigue can also have other causes: http://bit.ly/P168QB

    This study concludes: Prior dideoxynucleoside analogue (d-drug) exposure (P = 0.016) and the presence of clinical lipodystrophy syndrome (P = 0.011) were associated with fatigue.

    HIV Med. 2012 Sep 23. doi: 10.1111/j.1468-1293.2012.01050.x. [Epub ahead of print]

    HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms?

    Source

    Department of Infection and Tropical Medicine, Royal Victo, ria Infirmary, Newcastle-upon-Tyne, UK; Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK.

    Abstract

    OBJECTIVE:

    The aim of the study was to determine the prevalence and risk factors for HIV-associated fatigue in the era of highly active antiretroviral therapy (HAART).

    METHODS:

    A cross-sectional survey of 100 stable HIV-infected out-patients was carried out. Severity of fatigue was measured using the Fatigue Impact Scale (FIS). Symptoms of orthostatic intolerance (dysautonomia) were evaluated using the Orthostatic Grading Scale (OGS). Data for HIV-infected patients were compared with those for 166 uninfected controls and 74 patients with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (encephalopathy) (ME).

    RESULTS:

    Ninety-one per cent of HIV-infected patients were on HAART and 78% had suppressed plasma HIV viral load (≤ 40 HIV-1 RNA copies/mL). Fifty-one per cent of HIV-infected patients reported excessive symptomatic fatigue (FIS ≥ 40), and 28% reported severe fatigue symptoms (FIS ≥ 80). The mean FIS score among HIV-infected patients was 50.8 [standard deviation (SD) 41.9] compared with 13.0 (SD 17.6) in uninfected control subjects, and 92.9 (SD 29.0) in CFS patients (P < 0.001 for comparison of HIV-infected patients and uninfected controls). Among HIV-infected patients, fatigue severity was not significantly associated with current or nadir CD4 lymphocyte count, HIV plasma viral load, or whether on HAART. Prior dideoxynucleoside analogue (d-drug) exposure (P = 0.016) and the presence of clinical lipodystrophy syndrome (P = 0.011) were associated with fatigue. Additionally, fatigue severity correlated strongly with symptomatic orthostatic intolerance (r = 0.65; P < 0.001).

    CONCLUSIONS:

    Fatigue is very common and often severe in HIV-infected out-patients, despite viral suppression and good immune function. In a subgroup of patients, prior d-drug exposure may contribute to fatigue, suggesting a metabolic basis.Dysautonomia may also drive fatigue associated with HIV infection, as in other chronic diseases, and CFS/ME, and should be further evaluated with the potential for a shared therapeutic approach.
    © 2012 British HIV Association.

    FDA approved Jak inhibitors and their potential use in HIV – Interview with Dr Raymond Schinazi

    As part of my
    work as a cure and salvage treatment activist, I am constantly searching for
    treatment options that could serve two purposes: existing medications that
    could help patients with multidrug resistance and at the same time be used as
    an approach to cure HIV.  Since my non
    profit (Program for Wellness Restoration) has a very small budget for me to
    attend conferences, I rely on summaries that Jules Levin and his group
    (NATAP.org) publishes after he attends conferences.  I am glad Jules can serve as eyes and ears for
    those of us unable to attend so may important scientific meetings.
    Rarely I come
    across information about a drug that is already available and which can treat
    HIV and hopefully also help decrease its reservoirs. While reading
    one of NATAP’s great summaries about the recently held  International Workshop on HIV and Hepatitis in Sitges (June
    5-9) I came across a completely new approach that could meet the two goals.
    One of the abstracts presented by Dr Raymond F Schinazi and
    colleagues was on the topic of a novel series of inhibitors of HIV replication
    called Jak inhibitors. The Jak-STAT pathway is routinely stimulated in
    HIV-infected cells and can therefore be perceived as a logical target for drug
    development. Dr Schinazi’s proof of concept study showed that two  compounds termed Tofacitinib (to be approved
    soon by the FDA for myeleofibrosis) and Jakafi (already approved by the FDA
    for rheumatoid arthritis) demonstrated excellent inhibition of HIV replication
    at very low concentrations in vitro as well as against replication of a SHIV
    in  rhesus macaques. Moreover, these
    compounds were not toxic at the very low doses required for virus control. The
    data also suggest that these compounds might interfere with the ability of HIV
    to achieve latency in a variety of target cell types and that they were active
    against all of a variety of forms of drug-resistant HIV that were tested. In
    addition,  these compounds seem to re-activate
    latent virus hidden in reservoirs, which may help with the
    “flush-and-kill” approach being studied as part of HIV cure research.

    I contacted Dr Schinazi and he was happy to speak about his findings.
    Raymond F. Schinazi, PhD, DSc is the Frances Winship Walters Professor
    of Pediatrics and Director of the Laboratory of Biochemical Pharmacology at
    Emory University. Dr. Schinazi is the founder of several biotechnology
    companies focusing on antiviral drug discovery and development, including
    Pharmasset, Triangle Pharmaceuticals, Idenix Pharmaceuticals, and RFS Pharma.
    He has published over 400 peer-reviewed papers and 7 books, and holds more than
    100 U.S. patents. He is best known for his innovative and pioneering work on
    FTC (emtriva), 3TC (lamivudine), d4T (stavudine), LdT (telbivudine), and DAPD
    (amdoxovir), drugs that are now approved by the FDA or are at various stages of
    clinical development. His inventions now sell more than US$2.0 billion per year
    and more than 94% of the HIV-infected individuals take at least one of the
    drugs he invented. Dr. Schinazi has served on the Presidential Commission on
    AIDS and currently serves on the Board of Trustees of AMFAR. Due to his many
    business accruements and notable academic accomplishments, Dr. Schinazi is
    internationally recognized as one of the most influential persons in the life
    science sector.
    Nelson Vergel:            Dr Schinazi,
    thank you so much for taking the time to talk to us at TheBody.com. When I did
    a search on the Internet about your work I was blown away. I’m just blown away
    by all the work, all the patents, published papers and the books. So thank you
    because I know you must be a busy person.
    Dr. Raymond  Schinazi:          It’s no problem, I’m well known
    actually in the scientific world, not in the public.  I try to keep a low profile, usually, which
    is hard because when you search my name on the Internet, you probably find so
    much, but not everything there is true.
    Nelson Vergel:            Well, I
    have to say I’ve been positive for 27 years and  that your work
    has definitely made a difference in my life now that I know what you’ve done.
    Dr. Raymond  Schinazi:          Well, if you’re HIV infected, it’s
    very likely you’re taking one of my drugs. So I am happy to have been of
    assistance to you personally.
    Nelson Vergel:            Yes, of
    course, you definitely have.
    Dr. Raymond  Schinazi:          I’m also the founder of Pharmasset,
    which is the company that has one of the best phase 3 HCV drug  which  was
    sold in January 2012 for 11.4 billion dollars to Gilead.  I believe this  drug will also save a lot of lives and cure a
    lot of people from this devastating infection that affects 3% of Americans.
                Now we’re working on
    curing HIV, so that’s why I think what we’re doing here with this JAK inhibitor
    is really important.
    Nelson Vergel:            it’s
    amazing what you’ve done.                        
                                    
    Could you please tell us about the abstract that you presented at the
    recent  International Workshop on HIV and
    Hepatitis in Sitges  about  JAK inhibitors ?
    Dr. Raymond  Schinazi:          There’s this pathway basically called
    the JAK-STAT pathway, which is very important for HIV because it is activated
    upon HIV infection, so anything you can do to suppress it is a good thing, very
    simply. Basically, inhibition of the JAK-STAT pathway in addition could provide
    a mechanism to do several things; one, and something we didn’t expect, inhibit
    HIV application in HIV infected cells and actually that was something we
    discovered for the first time demonstrating this JAK inhibitor, had intrinsic
    anti-HIV activity. In addition the JAK inhibitor renders bystander cells less
    susceptible to HIV infections by down regulation the activation stage. In
    activation stage, basically the normal cells that are surrounding the infected cells
    becomes less susceptible to HIV, which is a good thing because it prevents the
    virus from spreading to these cells.  It
    also prevents the recruitment of uninfected cells to the site of infection. A
    really major mechanism of the JAK inhibitors is they reduce inflammation
    also.  There are a whole bunch of
    pro-inflammatory cytokines that thrive when HIV infects the cells and JAK
    inhibitors can ablate these effects. 
    This is not something new; we have known
    for some time the mechanism of these JAK inhibitors. They are used primarily
    for rheumatoid arthritis and  autoimmune
    psoriasis.  They are used for various
    cancers and one of them is actually approved for myelofibrosis.  All these facts put together make these
    compounds ameanable for testing to help suppress HIV and also reduce
    inflammation.  I think inflammation is a
    very important factor in HIV infection, not only at the site of infection,
    wherever active virus is but also for cardiology and do you know there has been
    a strong relationship between the heart and HIV, people even have sudden
    death.  In a recently published paper
    that came out, people die of HIV from heart attacks or cardio disturbances
    because they’re HIV infected.  So, it is
    a good thing that these compounds could reduce the inflammation in addition to
    preventing the virus from replicating, preventing the virus from spreading and
    also suppressing virus replication at the cellular level unlike normal
    antiviral agents, which basically interfere with the virus machinery and
    ability to replicate themselves. 
    Basically after working on the virus, these JAK inhibitors also act on cellular
    mechanism associated with inflamation..  
    There
    are lot people involved in trying to cure HIV. 
    They are actually activating the latently infected cells and trying to
    destroy them since they now become visible to the immune system, trying to
    destroy the cells and the virus contained in these cells.  Despite activating the virus from these cells,
    the cells are not totally destroyed so all these approaches, in my personal
    opinion, will probably not work. So, I am concerned about this and I’m sure
    you’ve written about this before or you’ve spoken to other people.  So, I’m thinking differently and during the Sitges
    meeting I was the only person talking about suppressing HIV rather than
    activating this virus.  You know, we have
    in our body maybe 50 to 100 viruses right now and most of them are suppressed.
    They don’t bother us and that’s why we can live a normal life. When our immune
    system is debilitated, the viruses come out. For example, chicken pox infection
    is common when you’re a kid; but the same virus becomes varicella-zoster when
    you’re older. We have viruses all over our body, like we have bacteria too all
    over our body, so nothing’s new there. 
    My philosophy is to suppress, and end up with  a “functional cure”.  That’s what I’m interested in, functional
    cure, rather than an eradication cure. This is going to be very hard to do.
    Even with a Berlin patient, as you well know, it’s been extremely hard to prove
    a negative, i.e., that the patient is really cured and that there is no trace
    of virus in his body.
    Nelson Vergel:            Yes
    Dr. Raymond  Schinazi:          There is residual RNA or DNA present
    in the body of the Berlin patient that we don’t quite understand.  I’ll call his cure a  “functional cure,” not actually a complete
    cure, despite what people may say. However, there is hope that you can actually
    do it and we would like to try to use the best JAK inhibitors, as I said, one
    of them is approved: Jakafi is approved by the FDA, which is used for
    myelofibrosis. Eventually this drug will also be approved for rheumatoid
    arthritis, autoimmune psoriasis and also various other kinds of conditions.
    There other drugs that are being developed in the same class for rheumatoid
    arthritis that will basically replace injectable anti-TNF alpha therapy, which
    as you know can reduce inflammation, but with a number of side effects.  So again, these are new modern drugs, which
    are coming out that have this utility that we’re trying to apply for HIV.
    Nelson Vergel:            I was
    reading about a JAK inhibitor called Tofacitinib, a drug made by Pfizer that
    got reviewed last month for a rheumatoid arthritis indication. I guess this
    drug will probably be approved by the FDA soon.
    Dr. Raymond  Schinazi:          We will know in August 2012.
    Nelson Vergel:   Yeah, it looks pretty good; low side effect
    profile and BID dosing. I was looking at the in-vitro data here you presented
    at the conference.  The dose you used
    ranged from 0.02 to 0.3 micro-molars. How does that dose translate if used in
    humans? Also, are you proceeding with studies in humans?
    Dr. Raymond  Schinazi: 
      These drugs are given a dose of
    20 mg per day, very small pills, because at a higher dose they’d probably have
    some side effects. We will plan on using initially the smallest doses and they
    come in different sizes. I foresee using different inhibitors of different JAK
    pathways inhibitors for patients who are infected with HIV. What we do now is
    that the JAK inhibitors could be dosed to provide blood levels in the
    nano-molar range.  As mentioned, one is
    already approved for chronic long term use in humans, which is important and
    interestingly. Some of these compounds, but not all of them, are CYP3A4
    inhibitors, meaning they can actually boost protease inhibitors, for example.
    It’s like ritonavir boosting. That’s actually very interesting as well.
    Nelson Vergel:   I guess you’re thinking about proceeding with
    human pilot studies, too, and how is that going to happen?
    Dr. Raymond  Schinazi:    I’ve
    already spoken officials at NIH as well and to physicians who specialize in viral
    eradication. They’re trying everything and the kitchen sink. The fact that this
    drug is already approved and under controlled conditions, we’re planning to do
    a carefully designed clinical study.  We
    want to do this in monkeys first as a proof-of concept, but I think there’s
    enough interest among some of the physicians I’ve talked to perhaps do a small
    pilot study and see whether indeed this works the way it’s supposed to.  This is all very new stuff. So we’re gearing
    up towards that and we hope that we will get our protocol approved so we can
    actually try it in humans. It’s also a question of getting some funding for
    that study, but it’s a small number of patients because it’s a high risk, high
    return and I don’t think the drug on its own is going to be enough.  We need to basically find patients who are already
    virus suppressed on HAART and add on this molecule for a few months and
    eventually take off the other medication and see what happens; see if the virus
    gets reactivated or reactivation is delayed. 
    You have to select very carefully the population of patients that you’re
    going to use for the study; they shouldn’t be very sick and we have to be
    careful because resistance could be an issue especially in patients who’ve had
    HIV for a long time. So you don’t want to withdraw treatment unnecessarily. The
    patients have to be monitored very carefully. We also have to develop better
    methods for detecting virus at very low levels. It’s something that we can do
    now with the technology available for that purpose. That’s why I wanted to do
    this in monkeys first, but as I said some of my colleagues indeed would like to
    go straight into humans.
    Nelson Vergel: Will the
    funding come from the NIH or from any of the companies like Pfizer? Are
    they interested in this kind of indication?
    Dr. Raymond  Schinazi:    I
    cannot talk because I’m a CDA with the company. 
    I cannot discuss which company. 
    All I can tell you is I’m working with a company at this stage, trying
    to look at better drugs that would have lower toxicity and be safer to use
    specifically for this purpose.  I don’t
    know whether they have funds for this study.  We have other resources and for a pilot study it will not be costly.

    Nelson Vergel:   Yeah. 
    Let me give you a little background onmy work in HIV.  I’m research advocate, as I told you I’m an
    HIV positive patient myself and do a lot writings and educational programs and
    work with different committee advisory boards for pharma and FDA and all that.  As part of that work I’m part of what we call
    an HIV cure working group.  There’s maybe
    eight or nine of us around the country meeting with researchers.  We actually just organized a really  good meeting to review different cure related
    approaches. I have a summary I can actually email to you and we’re planning to
    do another one of those review meetings maybe at the end of the year or so.
    Also, actually I’m probably the number one advocate when it comes to multi-drug
    resistance and salvage access because I myself have multi-drug resistance. So that’s
    why I just jumped on when I read this paragraph in the summary, I jumped for my
    own case because some of us even though there are lots of treatments out there
    are on our last basic combination therapy and some of us may or may not
    suppress the virus for many years.  I’m
    in a research study using a monoclonal antibody and maraviroc, which is
    research drug.  We’re still alive and
    doing well and hopefully praying that our viral load doesn’t go up and we run
    out of options because the pipeline is looking a lot drier nowadays.  That’s why my work in the cure research and
    also salvage therapy made me very interested in your work with JAK inhibitors,
    so if you ever need any community advocacy, meaning letters of support for your
    approach for the NIH, we do that.  If you
    ever need, for instance you’re doing a pilot study and have a very specific
    target of patients that you want to enroll, we also spread the word really fast
    in the community for – Actually I just finished a survey that I’m going to
    publish in JAIDS on the risk tolerance of patients when it comes to cure
    related studies because nobody really knows whether some patients are going to
    altruistic enough to like you say, stop their meds after being suppressed and
    what we have found is that 80% of patients, over 3,000 patients answered the
    survey, are altruistic.  They really want
    the cure and are willing to take certain risks even though most of them are
    doing well.  There is a lot of, and I’m
    glad we’re bridging right now, there is a lot of community support behind
    approaches like the one you’re taking and I want you to be aware of that so if
    you ever come across to a brick wall and there is a lot of that sometimes in
    this.
    Dr. Raymond  Schinazi:    Let
    me tell you I didn’t get to where I am by accident, Nelson, I’ve had many brick
    walls; I’ve smashed them to get to where I am today.  I’m originally Italian; I think you’re
    Italian, at least you sound Italian.
    Nelson Vergel:   I’m Venezuelan.
    Dr. Raymond  Schinazi: I would love to meet you face to
    face, I’d like to know more about what you’re doing and if you can help
    certainly I’ll keep you informed on what’s going on.  We have a very strong group here at Emory
    University.  The nice thing about the
    drug that I’m working with is that it’s already approved by the FDA, so it
    should be a lot easier to test in humans.
    Nelson Vergel:  That would be great! Thanks again for taking
    the time to give us an update on your very exciting work.  I will reach out to you in the future to
    check any progress in non-human primate and human studies.

    Fw: Hot Topics at TheBody.com’s “Ask the Experts” Forums

    From: “News at The Body” <update@news.thebody.com>
    Date: 18 Sep 2012 18:37:02 -0400
    To: <nelsonvergel@yahoo.com>
    ReplyTo: “News at The Body” <update@news.thebody.com>
    Subject: Hot Topics at TheBody.com’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

    September 18, 2012 Visit the Forums “Hot Topics” Library Change/Update Subscription



    Living With HIV  Will It Kill My Mother to Hear That I’m HIV Positive?
    I just found out I’m HIV positive. I live with my parents and I think I need to tell them, because I worry the next few weeks will be harsh and they’ll definitely notice something’s wrong with me. But I’m really scared of my mother’s reaction. She’s very sensitive and her own health is not great; I don’t want to make things worse for her. She was always proud of me and thought I’d have great future. I feel terrible for potentially disappointing her. Do you have any thoughts or suggestions about this?

    Nelson Vergel responds in the “Nutrition and Exercise” forum

     What Can We Do About Vitamin D Deficiency?
    I read a recent study stating that a large percentage of the HIV-positive community is vitamin D deficient. I know many doctors are skeptical about the benefits of supplements, but what are we supposed to do about a lack of this important vitamin in our bodies? Would you please shed some light on this issue?

    Benjamin Young, M.D., Ph.D., responds in the “Choosing Your Meds” forum
    Mixed-Status Couples  How Can I Get Comfortable With the Man of My Dreams?
    I met a wonderful person who I think may be the man of my dreams. We met on an STD (sexually transmitted disease) dating website because I have herpes. He listed he had herpes as well, but as we got to know each other he told me he also has HIV. He’s on medications to keep his viral load down and it’s currently undetectable. Emotionally I’m worried about getting attached and then something happening to him. I’m also a little fearful of our sex life. I want to give myself to him but I still don’t feel 100 percent comfortable, even with protection. How can we have a fulfilling relationship while keeping the HIV transmission risk low?

    Richard Cordova responds in the “Safe Sex and HIV Prevention” forum
    Insurance, Workplace & Legal Concerns  Can I Sue My Doctor if My Off-Label Med Regimen Fails?
    I have had an undetectable viral load since starting HIV meds with Sustiva (efavirenz, Stocrin) and Truvada (tenofovir/FTC) in 2005. About six months ago my doctor noticed some kidney damage and recommended I start taking Truvada every other day while continuing to take Sustiva every day. I was skeptical as it’s not a published regimen, but I was assured that this had worked well in others, so I changed my dosage in this way. My viral load was undetectable at three months; now at six months it’s detectable at 1,345 copies/mL. Since this regimen is not approved — or even studied, to my knowledge — is there the potential that this could be malpractice?

    Christa Douaihy, Esq., responds in the “Legal Issues and HIV” forum

     Do I Have to Pay Back My Social Security Disability Payments?
    I went back to work after 13 years on disability. The Social Security Administration kept paying me for a long time after I went back to work. Now they want me to repay the amount they paid, even though I told them several times to stop the payments. What will happen when I get to retirement age, which is fast approaching, and I need to receive social security payments but I can’t because I’ll still owe them thousands of dollars? What can I do about this situation?

    Jacques Chambers, C.L.U., responds in the “Workplace and Insurance Issues” forum
    Visual AIDS: Art from HIV-Positive Artists
    Image from the September 2012 Visual AIDS gallery Detail from:
    Untitled, 1993-1996
    Nelson Edwin Rodriguez

    Visit the September 2012 Visual AIDS Web Gallery to view our latest collection of art by HIV-positive artists! This month’s gallery, "Elegy for a Queendom That Never Became," is curated by Quito Ziegler.


    HIV/AIDS Treatment  Why Is My Semen So Watery After Taking Atripla?
    Ever since I started taking Atripla (efavirenz/tenofovir/FTC), my semen hasn’t been the same. It used to look much healthier but now it’s very watery, almost clear. I don’t have any infections. My diet and habits are pretty regimented — normal sleeping patterns, low levels of stress, proper eating — and Atripla is the factor that stands out as the possible culprit. What could be going on?

    Keith Henry, M.D., responds in the “Managing Side Effects of HIV Treatment” forum

     Can I Switch to Complera Even Though I’ve Taken HIV Meds Before?
    I’ve been taking Norvir (ritonavir), Reyataz (atazanavir) and Truvada (tenofovir/FTC) for a few years and my T-cell count has never gotten past 475; at last check it was 300. I also suffer from stomach distress, and my eyes and skin have taken on a yellowish hue. I believe the Norvir/Reyataz part of my combo is the culprit, and Complera (rilpivirine/tenofovir/FTC) would address this by replacing it with another drug. I’ve read that Complera shouldn’t be taken if you’ve already taken HIV meds. Why is this? Would it be safe for me to try Complera?

    Benjamin Young, M.D., Ph.D., responds in the “Choosing Your Meds” forum
    Other Health Issues & HIV/AIDS  Can HCG Reverse Testicular Atrophy After Long-Term Hormone Use?
    I’m a 52-year-old man; I’ve been HIV positive for 26 years and had an AIDS diagnosis for 16 years. For the past decade I’ve been receiving weekly Depo-Testosterone injections. In recent years my testicles have shrunk dramatically, often retreating up inside my body, especially when I’m sexually aroused which causes pain and embarrassment. I’ve read that human chorionic gonadotropin (HCG), given alternately with the testosterone, might stimulate re-growth. My doctor believes it’s too late, plus I’m told HCG isn’t covered by ADAP (AIDS Drug Assistance Program). What are your thoughts on the matter?

    Nelson Vergel responds in the “Aging With HIV” forum

     Does My Chronic Hepatitis B Need to Be Treated?
    I’m a 25-year-old woman, I’m HIV positive and I have chronic hepatitis B (hep B). I’ve been taking HIV meds for 10 years and I’m currently taking Combivir (AZT/3TC), Lexiva (fosamprenavir, Telzir) and Norvir (ritonavir). My CD4 count is somewhat stable around 500 and my viral load is undetectable. My liver tests are normal, but what do you think that means? Should I be taking treatment for hep B? Are the meds I’m taking now good for hep B too? Is there a chance my hep B is completely healed?

    Barbara McGovern, M.D., responds in the “Hepatitis and HIV Coinfection” forum
    gay men's resource center
    TheBody.com’s HIV/AIDS Resource Center for Gay Men serves up a vast amount of knowledge, first-person perspectives and a wide range of articles to provide gay men and allies with must-have information.

    In this resource center you’ll find:
    Gay Men's Resource Center

    • Up Close & Personal: First-person stories and columns from gay men living with HIV.
    • Info & Advice: Here’s where you can turn to for current statistics and facts, advice on safer sex, information on where to find support and more!
    • Hot-Button Issues: This section boasts exclusive roundtables, our Word on the Street slideshows and special reports all related to gay men.
    • Q & A: Our trusted professionals weigh in on readers’ questions.

    TheBody.com’s HIV/AIDS Resource Center for Gay Men was created for both HIV-positive and HIV-negative men to have a safe place to consume HIV/AIDS information. We hope you enjoy it and find it useful!


    Understanding HIV/AIDS Labs  What Are My Virus’ Chances of Developing Resistance?
    I’ve been HIV positive since 2010 and taking Atripla (efavirenz/tenofovir/FTC) for almost all the time since. What terrifies me is that my virus might develop resistance and I’ll have to switch to stronger medicines and my number of pills, side effects and cost will increase. I don’t have many options to fall back on should something go wrong. So far things have been fine — my viral load is undetectable and my CD4 count is stable. Do you think my chance of developing resistance is high? Should I keep worrying? What else can I do?

    Benjamin Young, M.D., Ph.D., responds in the “Choosing Your Meds” forum
    HIV Transmission  Binge Drinking, Unprotected Sex and Anxiety: Which Is More Risky for Me?
    I’m a heterosexual female. I suffer with anxiety, especially when it comes to the fear of contracting HIV. Recently I had unprotected vaginal sex with a man of unknown status seven times. I went to a sexual health nurse who convinced me I didn’t need to be tested for HIV. About two weeks ago I got drunk and had sex with another man I’d just met, this time while intermittently blacking out. At some point he took the condom off but I can’t remember if we had sex without it or not. What are your thoughts on this scenario? Do you think I was at serious risk for becoming HIV positive?

    David Fawcett, Ph.D., L.C.S.W., responds in the “Mental Health and HIV” forum

    Worried Your Spam Filter Might Trash Our Mailings? The Body’s e-mail updates are especially prone to being caught up in spam filters, since our newsletters tend to refer frequently to sex, drugs, the human anatomy and so forth.

    To make sure you never miss one of our mailings because anti-spam software labeled it as junk mail, add update@news.thebody.com to your address book, talk to the person who manages your e-mail security or check your anti-spam program’s instructions for more information. About This E-mail This e-mail update has been sent to nelsonvergel@yahoo.com.

    Want to change your subscription? Click here or send us a message at updates@thebody.com.

    Missed an update? Our archive of past updates will keep you in the loop.

    Have any other questions or comments, and don’t want to send an e-mail? Feel free to snail-mail us at:

    The Body’s E-Mail Updates
    Remedy Health Media, LLC
    250 West 57th Street
    New York, NY 10107



    Follow Us
    Facebook  Twitter
    Activist Central
     Movie Event: Celebrate Our History and Build Our Movement

     Call for Abstracts for the 2013 National Af-Am MSM Leadership Conference in L.A.

     Tell Your Representative to Support Cure for AIDS Act!

     Train and Triumph With Team to End AIDS!

     Under Attack: Your Health Care Rights