byline: Larry: Babble and Meddle

byline: Larry: Babble and Meddle: "It should be ironically hilarious that there was no end of the world and no rapture. It should be, but it isn’t. Really this pathetic d..."

Babble and Meddle

It should be ironically hilarious that there was no end of the world and no rapture. 

It should be, but it isn’t.  Really this pathetic desperation of some to avoid dying, at all costs, looks like a scene from the transporter room aboard the Starship Enterprise.  Essentially, that’s what it was, a human imposed contract with God to get out of a tough act easily.  Apparently, no one thought to ask God if It agreed.  Apparently It didn’t.  One can only assume the 89 year old self appointed VOG (voice of God) on the subject was left hugely embarrassed by God’s lack of participation.  Maybe not, but since his big meeting with the great, universal CEO must be fairly near, that particular arrogance may require some quick step explaining soon.

God condemned Adam, and Eve, to live, suffer, toil, and die.  Through “original sin”, we were all damned to die after them, forever.  God said; for dust thou art and to dust shalt thou return, Genesis 3:19.  It is probably one of the clearest statements in a book that’s often obscure, filled with man-made babble and meddle, and open for whatever interpretation from whoever feels moved by it, for good or ill. God didn’t moderate his condemnation by saying, except in the case of a rapture, which I’m still thinking about. 

The Bible is the perfect manipulative document. The concept of the rapture is an equally perfect example of people narcissistically attempting to go round the rule of death.  I knew a guy like that once.  He never met a rule he didn’t believe could be bent some which way to his personal advantage.  He simply didn’t get the integrity of following the rules that must be followed. He’s been dead a long time.  I struggle over what to have for lunch.  Old Mr. Camping, however, found it easy to announce the end of the world, presumably over lunch. Did he speak from secret knowledge or secret desire?  Perhaps it was fear, or greed. 

I’m not going into what death truly means because I don’t know.  I haven’t been there and therefore have no basis upon which to argue.  That doesn’t bother me, because you don’t, either, unless you’re already dead, which I very much doubt.  I can talk about its impact on living. Rapturists and other death escapists are like the saying, when an irresistible force meets an immovable object.  Apply all amount of pressure you want on God and bend every rule you can conceive of, but death will not be moved.  It is there, as firmly set as birth and taxes.  We all must one day accept its embrace. 

Certainly death isn’t that bad.  After all, everyone who was ever born, except those of us alive today, has died.  Every one living now, or will live, will do it, too, so it seems like a pretty popular gig at a 100% rate of participation.  I suspect that where we go after death is very probably the same place we came out of when we were born (go ahead imagine a dirty metaphor. I don’t mind).  Now, for the sake of fairness, and bowing to the infestation-like populating we do, maybe the newborns couldn’t wait to get out of there.  Maybe it ain’t such a swell place at all.  But maybe it’s something we are unable to grasp.  Something completely terrific. 

Most likely, I think, it’s that we are only visitors here from a wonderful, unknowable other place or dimension.  We come with no baggage, we leave with no baggage, but the imprint we make is indelible.  I believe that each of us was sent here to experience, take that back with us, and relay to the Great Mind what we’ve seen and who we’ve been.  Looking on it that way, I see that living is one great, hopefully long drawn out, rapture.  Those among us who would write it in shorthand, which risks befouling the legacy of Christ, only end up shorting themselves.  In the presence of the constant fear of death, one can’t live.  The fear of death, then, is really a fear of living.  No rapture could be as sweet as not fearing to live.

Beam me up, Scotty.

Kirk out. 

byline: Larry: Monkeys Shine.

byline: Larry: Monkeys Shine.: "You can’t make a monkey out of me. Or, can you? Like HIV/AIDS, HCV has a simian brother, the chimpanzee. They are the only animal bes..."

Monkeys Shine.

You can’t make a monkey out of me.  Or, can you?  Like HIV/AIDS, HCV has a simian brother, the chimpanzee.  They are the only animal besides man that can be infected by HCV.  A research foundation in San Antonio uses 35 animals as test subjects, and they do it as humanely as possible.  They applied a gene based therapy called blocked nucleic acids to chimps infected with HCV.  The therapy does not target the virus, instead it blocks molecules necessary for virus replication.  It essentially starves the invader.  The results were astounding.  A 350-fold viral drop lasted up to three months after therapy was ended.  Better yet, no antiviral resistance was demonstrated.  Even better, the liver begins to heal itself rather rapidly during therapy.  Researchers claim this is a major breakthrough.  You must view the CBS-news video.  Looks like Cheetah could come to the rescue of Tarzan yet again. 

Now it’s time for a disclaimer.  Last episode I cited a recent EASL conference report on the interactions of HIV meds and HCV meds.  The report stated that there was little interaction.  Sources deep inside a major national health care provider now cite a later report.  The report found that interactions are a great deal more serious than initially thought.  In fact, some HIV meds would need to be dropped or changed entirely during HCV treatment.  The HIV protease inhibitor, Darunavir (prezista), for instance appears to be entirely incompatible with both telaprevir and boceprevir.  Other compounds for HIV, i.e. tenofovir, may experience rises or depressions in the drugs’ blood levels in the presence of HCV meds that may require dosing adjustments.    

Family Health International (FHI) announced disappointing news about women and HIV.  The so-called FEM-PrEP trial of emtricitabine and tenofovir disoproxil fumarate for preventing HIV infection in at risk women will be stopped after an interim review indicated its effectiveness was unlikely.  Once again the ladies get the short straw. 

Bavituximab is an investigational monoclonal antibody that targets a certain phospholipid component on the membrane of virus-infected cells. Preclinical studies have shown that this type of antibody can inhibit viral replication and enhance immune response.  The phospholipid component expressed on cells infected with a variety of viruses, including HCV, HIV, influenza, and herpes viruses, suggesting that targeted antibodies could be beneficial in a number of diseases.  An experimental monoclonal antibody that inhibits HCV replication was safe and well-tolerated in a clinical trial of HIV positive people coinfected with chronic hepatitis C.  Earlier studies found that twice-weekly intravenous infusions of Bavituximab of up to 6mg were well tolerated and showed antiretroviral activity in people with HCV. 

Say, let’s not abandon the Bavituximab story just yet.  Another EASL study released on April 15, found that Bavituximab is well tolerated and safe for co infected HIV’ers.  I think we’ll be hearing a good deal more about this compound very soon.

For my final word I’ve selected ‘HCV and the arts’.  Is this a co infection issue?  Well, yes it is because if you search for films, plays, still-art, etc. for themes on HIV/AIDS, you’ll be overwhelmed with the number of hits.  For instance, since 1984 there have been over 120 films with significant or main themes concerning HIV/AIDS from almost two dozen countries. The first known documentary HIV/AIDS film was the United Kingdom’s 1984 release called Bright Eyes.  The first American film was titled Buddies released by New Line Cinema, 1985.  How about television?  NBC did it first in 1985 with its premiere of An Early Frost, which began a series of AIDS as disease-of-the-week movies that presented fictionalized and true stories on such notables as Liberace, Ryan White, and Roy Cohn.   

Counter that with a search on the arts and HCV.  You’ll find practically nothing, except some very short YouTube informational videos.  It’s not for a lack of subject matter.  After all Natalie Cole, Naomi Judd, Larry Hagman, and Pamela Anderson all battle HCV.  Just in the U.S., more people infected with HCV are alive today than have been diagnosed with HIV – ever.  And, HCV is older than AIDS.  Discovered in 1988, scientist had been searching for the elusive virus they dubbed hepatitis non-A, non-B since 1975.  It begs the question, why has HCV been virtually ignored in the dramatic arts? 

One of the things art does is illuminate and inform.   Illumination quantifies a difficult subject and informs us on an entirely different, visceral level about it.  I don’t have an answer to the question of why one virus is well covered in the arts and the other, cousin virus, is not.  So, I won’t ask.  That doesn’t mean I can’t speculate.  HIV/AIDS was a crash disease in the beginning.  Wham, bam, gone!   HCV ambles along slowly for many years before reaching another long, drawn out process leading to end stage.  One is sensational in its impact, the other not so much, though the paths of each lead to the same destination.

AIDS is sensational because it happens today.  HCV is not because it happens tomorrow.  HCV remains fairly regular looking for a very long time.  With AIDS the downfall was swift and could be readily seen on the faces and bodies of HIV people.  Plus, HIV is considered sexual, giving it a certain cachet. Yet, HCV should be included in the conversation that the dramatic arts empower.  Is there not a talented play-write, screenwriter, paint artist, or just some bloke novelist with an ear to the obscure out there who can see the ripeness of the HCV struggle?  Or, for that matter, HCV and HIV together.   What we call co infection.

It’s too much.  I think I’ll just go have another banana.  Cheetah, who is still alive and living in my town, has offered to be my designated driver.

Where the hell is Harry?

The train to Disneyland seems to have gotten off rail somewhere ending up in Congress instead.  No one from the Mad Hatter’s Tea Party has noticed the mix up.  They apparently believe it really is a party where everybody ought to grab what they can for themselves.  They keep passing the mad hat of responsibility around from one unlikely nutcake to the next.  For those who went there specifically to rant and rave it’s one thing.  For the President who promised to protect us from corporations and Wall Street it’s another Tinkerbell altogether. 

We’ve used Harry as a dubious homage to Irving Berlin’s Call Me Madam!  Ethel Merman plays a Perle Mesta type who is appointed to an ambassadorship by Harry Truman.  Harry kicked butts and the buck stopped with him.  For this President, where does the buck stop?  Does he even know what the buck is?  We knew Harry (from afar).  Harry was a friend of ours (from afar).  Mr. President, you are no Harry.

We’re continually amazed by how he’s quick to acquit himself of any responsibility.  No, it’s those pesky corporations and everyone knows they aren’t really people.  They’re dispassionate entities, automatons. We believe, however, that if you follow the string tied to corporations, somewhere along the string you’ll find people not only attached to it, but pulling it.  What Washington needs is a little more Harry and a lot less Goofy.  There are evil people up on that Capitol Hill.  Their agenda is to steal your future.  The President doesn’t seem to get it.  He thinks, we guess, that it’s ‘to the loser go the spoils.’  So, what do you think he’s going to do now?  We’re betting he’s going to Disneyland. 

Time to stand up, folks.  It’s your government and it’s your life.  Make a difference.  Now! 

-----

Now, two recent conferences are providing some very encouraging news for HIV/HCV coinfection.  First, the 18^th annual Conference on Retroviruses and Opportunistic infections (CROI 2011) reports the two new protease inhibitors for HCV, telaprevir and boceprevir, demonstrate minimal adverse interactions with most basic HIV meds.  Researchers believe that those interactions can be mitigated by simple dose adjustments.  That means there is a more than a reasonable expectation that those who are co infected can be safely treated.  One central question remains, however.  Will there be a resistance factor in HIV patients who are treatment experienced and very likely already resistant to several protease inhibitors?

The second conference, the 46^th annual European Association for the Study of the Liver (EASL 2011) says that Vertex’s telaprevir increased sustained response in all HCV people, regardless of IL28B status.  A whopping 90% SVR is associated with the best gene status, CC, with 78% able to cease treatment after 24 weeks.  Also, a nearly threefold improvement rate was observed among IL28B gene types CT and TT regardless of prior treatment experience. 

Ribavirin was approved more than ten years ago.  It remains the last med approved for treatment of HCV.  EASL reports that, in all likelihood, the coming decade in HCV research should be as wet as the last decade was dry.  There will very likely be, however, little impact upon the global incidence of HCV due to barriers of treatment access, ignorance, and stigma. 

Perhaps you heard that Johns-Hopkins researchers are arguing against a decade’s old law forbidding harvesting of healthy organs for transplantation from HIV positive people.  Of course, HIV positive patients would be the recipients of those organs.  South Africa has done HIV positive transplants with excellent results, but thus far, none have been performed in the U.S. due to this law.  HIV is now a manageable disease with medications.  HIV-infected donor organs may be transplanted into HIV infected patients. Doctors can call on the lessons and experience of transplanting HCV patients with organs from people with the same disease. This practice, which has not always been the standard, has substantially shortened the waiting list for these recipients without significantly compromising patient or graft survival. The decision of whether or not to use these organs is not a legal one, but one made by the clinician.

And last, it’s fairly well known that HCV infection may result in bone loss.  HIV also causes bone loss.  Put the two together and you have bone loss on steroids.  As time goes on, we will see more hip and spine fractures in our affected populations.  It won’t be pretty.  No sure fix for this problem is yet on the table because it is, by its nature, a complicated set of incidences that could be rooted in nutrition, metabolic systems, or other yet unknown causalities.   It is, however, interesting to note that almost all HIV and HCV people are Vitamin D deficient.   Some clinicians are advising Vitamin D3 supplementation.  Vitamin D3 is readily available over the counter.  Some caution should be exercised since overdose is possible.  One, 1000 mg of Vitamin D3 per day should be safe.  Resist the temptation to overdo this vitamin until more research is published.  Ask your doctor to check your Vitamin D3 levels at your next blood draw.

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Well, we’re going to Disneyland.  We’re taking Helena Handbasket along. 

byline: Larry: This is your brain on HIV and HCV.

byline: Larry: This is your brain on HIV and HCV.: "There was tough news out of the 2011 Conference on Retroviruses and Opportunistic Infections (CROI) concerning HIV and the brain. In t..."

This is your brain on HIV and HCV.

There was tough news out of the 2011 Conference on Retroviruses and Opportunistic Infections (CROI) concerning HIV and the brain.  In the study, HIV was found in the brains of all participants.  There is a strong belief among researchers that HIV causes systemic inflammation.   HIV damage in the brain appears in the second and third of the four stages (Freiberg Stages) prior to seroconversion to AIDS, when there is a peak in inflammation.  Brain changes were demonstrated as early as two months into infection, usually before seroconversion.  While the changes are subtle, cognitive function declined as much as 13% in the first year and 35% in the second.  Much of this brain harm is associated with <350 T4 helper count and increased inflammation.  The good news is that age and length of infection are not associated with cognitive decline.

Apropos to that, a Canadian research team at the University of Montreal believes they’ve found a long elusive reservoir where HIV hides out.  It has been a long held theory that it might be the brain, but viral levels in the cerebral-spinal fluid are significantly lower than that found in the brain. That doesn’t disprove the brain reservoir theory.  It is an indication, however, that the theory could be flawed. The Canadians believe they’ve discovered a true reservoir in certain long term immune system memory cells.  These cells tend to hang around sleepily for a very long time, activating only when they encounter an old foe, such as the mumps or measles.   

In HCV, cognitive implications were identified early on mostly by patients who termed it “brain fog”, describing the come and go disorientation and confusion they experience.  It is a condition associated with HCV that tends to worsen over time. It becomes especially problematical with such complications as hepatic stents (essentially, an in-liver bypass), asciites, and other associations where toxins build in the blood.  A distinction was, at one time, drawn between brain fog and hepatic encephalopathy (HE) as was noted in an HCVAdvocate article as far back as 2002.  Today, however, it appears that the only real distinction is in severity.  It’s noteworthy that patients view brain fog in an almost humorous manner, but hepatic encephalopathy is nothing to joke about.  Hepatitis-Central posts an extensive overview in very simple format that may be helpful for those dealing with any stage of HE. 

Researchers already knew that HCV affects the brain.  New studies show that even when serious liver damage hasn’t occurred, patients still suffer memory loss, have trouble concentrating, apathy, and depression.  HCV gets in the brain where it infects and replicates.  A build up of HCV proteins in the cell eventually kills it, drowning it in its own refuse, so to speak.  U.S. Centers for Disease Control and Prevention picked up this study from Canadian researchers and The Body issued a report on it last October. 

We know that the brain is a wondrous entity.  It has an uncanny ability to work around deficits and injuries if it’s taught to do so.  Look at Representative Gabrielle Giffords.  She took a high caliber bullet through her brain in January.  It is now April and she’s singing Twinkle, Twinkle Little Star, talking on the telephone, and making noises about running for the senate next time.  That’s completely awesome.  And we know some really cool strategies for exercising the brain so that we might avoid Alzheimer’s.  Those methods work.  They can divert Alzheimer’s completely, or delay its onset. 

Could it be that brain implications are cross dimensional regardless of the underlying disease or injury that cause them?  It begs the question, Are there strategies that might aid in at least slowing the rate of mental deterioration found in both HIV and HCV, separate disorders that share many similarities?  There are very long term survivors of HIV/AIDS who must have suffered HIV infection in the brain very early in the disease process.  Some are completely nuts, but most of us function fairly normally in society.   How do we determine why that is and if it can be applied to disease across a spectrum?

Living itself is like a virus.  It kills brain cells.  Given enough time there will be cognitive decline.  Deep research into this barely addressed phenomenon might bring positive results not only for those who suffer.  Would doing crosswords or learning a new language open heretofore unseen pathways to good brain health, and does anyone know a four letter word meaning ‘mentally competent”?

We would be remiss if we didn’t honor last week’s passing of a great lady.  She befriended our community when we were down, bereft of many friends.  There’s no need to mention her name.  The entire world knows who she was.  Very early she demonstrated what utter fools we can be in our often smug wisdom by teaching us that nothing matters, not even life, if we turn away from the trials of our fellow beings.  Goodbye, fair lady, may God bless you with rest.

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HIV

Good news about the new HIV med, Gilead’s elvitegravir.  It is the second, after Merck’s raltegravir (isentress), in the new integrase inhibitor class.  It’s proving to be ‘non inferior’ (or equal to) isentress in effectiveness.  This novel class of meds might offer a lot of hope for HIV infection, especially those who are treatment experienced and developing resistances.  Elvitegravir is near the end of its investigational process, lacking only peer review.  Down the pike is ViiV Healthcare’s dolutegravir, the possible third med in this class.  And by the way, there are whispers of a new boosting agent being studied, tentatively dubbed cobicistat.  Try saying that while eating peanut butter.

More good news, Qutenza™ (8% capsaisin patch) is being heavily touted to ease the pain of shingles.  We’ll see some of that same sort of market push to treat HIV related neuropathy in the near future.  According to Medline, a 30 minute application of the patch provides results that last up to three months.  Compounded from the active ingredients in chili peppers, you won’t see much right now about its uses for HIV.  Just wait.  The word is that it can cause some pain at the application site along with redness and itching.  These symptoms are usually mild and ease after the patch is removed. 

There’s one disturbing thing on the HIV front.  A man in NY with a history of male sex partners, previously treated for syphilis, but not HIV+, tested HIV+ after a living donor kidney transplant.  It can only mean the kidney infected the new host.  The screening process has improved over the years in the medical establishment, but we believe this indicates there is considerable room for improvement.

HCV

There was a little noticed story in February.  The FDA approved a finger stick test similar to that for diabetes.  It is the only FDA approved point of care rapid test for the detection of the presence of HCV antibodies.  By avoiding the need for a blood draw, this test offers a method to reach those who remain unaware as well as the 3 – 4 million new infectees every year.  That should lead to earlier treatment, before the virus has done its major messing around with our livers.  It’s a good thing. 

Absolutely the best news this week comes out of Canada.  Therapure Biopharma Inc. received a $350,000 grant from the National Research Council of Canada Industrial Research Assistance Program (NRC-IRAP). The company is currently developing hemoglobin, a natural blood protein, to serve as a drug carrier to improve the delivery of medications for Hepatitis C and Liver Cancer. It is expected to increase the supply of medication to the liver and reduce the drug's side effects.  What could possibly be bad about that?  We suspect it may lead to a whole new approach in near term treatments.

Ok, what do HCV and Epstein-Barr virus (EBV) have in common?  Well, no one seems to know.  According to Hepatitis Central, the two viruses should be completely distinct.  EBV is an easily contracted virus most of us already carry in a dormant state.  It’s a member of the herpes family.  Research has demonstrated a unique connection between HVC and EBV.  In the 08/99 edition of The EMBO Journal, EBV was detected in 37% of the tissues of hepatocellular carcinoma examined, most frequently in cases with HCV.  EBV may act as a helper virus for HCV replication.  Another connection between the two viruses appeared in the 12/10 Journal of Medical Virology. According to researchers, infection with HCV induces reactivation of EBV in B cells - an important cell in the immune system.  Research into this odd connection, and how it works, may well lead to better understanding of both.  There’s no reason to be nervous about this news.  One virus doesn’t appear to have much effect on the other.

COINFECTION

We’re relieved to learn there is little crossover sexually transmitted infection of HCV between European/Australian and U.S. gay men.  The reason for this is thought to be due to different genotypes.  U.S. men are almost always either 1a or 1b, while Europeans fall into an unusual strain of genotype 4.   Due to the highly charged nature of this subject, I always try to include the suspected links to sexual infection.  They are, but may not be limited to: unprotected anal intercourse, fisting, multiple sex partners, group sex, use of sex toys, nasal drug use, and presence of other sexually transmitted diseases; coinfected men typically do not report injection drug use.

Telaprevir with pegylated interferon plus ribavirin reduced HCV viral load to undetectable in about 70% of HIV patients at weeks 4 and 12 in the first phase 2 study of HCV/HIV coinfected people.  Hotly encouraged, Vertex Pharmaceuticals immediately announced it would launch phase 3 later this year.  In early studies, boceprevir also demonstrated positive results in coinfection treatment.  Interferon and ribavirin both have serious side effects.  Telaprevir and boceprevir each do, too.  So, each new med will contribute to greater rates of drop out.  Our understanding is, however, that the adverse effects are fairly limited to rash and itch.  Rash and Itch, they sound like evil twins, but we’re betting we’ll find ways to deal with them. 

EASL 2011 (The International Liver Congress) convenes in Berlin March 30 – April 3.

“So much to do, so little done, such things to be.” ~ Elizabeth Taylor

The Uninvited Guests

I’ve long believed that those who are co infected with the two uninvited, but seriously deadly cousins, HIV and HCV, are underserved.  Go to just about any clinical trial of new HCV fighting compounds and you’ll see that if you’re also infected with HIV, you’re not eligible.  Take it another step, co infections will be the last treated under any new protocol, and no one knows how dangerous such protocols might be for the co infected.  It’s not tough to leap to a conclusion.  Lately, though, my thinking has undergone some adjustment. 

Let’s run the numbers around quickly.  I promise not to bore you with a lot of statistics.  HIV/AIDS infections aviate somewhere over the rainbow of ‘more than a million’ in the United States.  It’s at about 1.2 to 1.4 million, depending on what arc of the rainbow you’re looking at.  Very far beneath it is the approximate 25 to 30% who are co infected.  That means some 300,000 or so people.  Believe it or not, that really is a very modest number. 

We’re not done here.  Let’s look at HCV/hepatitis C where U.S. infections hover around the five million level.  No, no more numbers, just the fact that the incidences of new infections leveled off a while back, and are now actually in decline.  What’s that about?  Certainly it’s not due to prevention and education.  Tell me where there is an out public push to educate anyone anywhere except maybe some dusty corners, or more likely, a few AIDS Service Organizations (ASO), and more spottily, the Veteran’s Administration.  Yeah, sure, the education amongst medical and dental providers has seen some effort.  Better care is taken today to ensure invasive equipment is properly sterilized, and that it is strict enough to knock off any HCV germy things that could be present.

Don’t get me started about prevention.  It hasn’t worked anywhere near an acceptable level in HIV.  Why would we expect it to work in HCV?  Remember, these two uninvited guests are first cousins.  Prevention efforts for both enjoy similar roadblocks in the human spirit.  We like to get high and we like to get it on.  They are the two main drags upon which HIV and HCV traverse.  Getting high and getting it on have been with us almost all the way, there isn’t a reason to feel they’ll die in the human heart any time soon.  In fact, they may be a very vital aspect of our humanity.  Ones that we will one day meet in a safe and meaningful way.  But not today.

So, what is it?  Why is HCV infections declining and what does it mean for co infection?  I don’t think anyone really knows what’s driving the decline, but it could be that the virus peaked, just as HIV will one day peak, and is on its way to becoming non lethal to humans.  We have a long history of physically assimilating viruses.  It might even explain the exceptional difference in our human intellect … that our brains supersized due to a virus.  Someday, hopefully sooner than later, HCV will no longer be a significant threat to us.  It would then mean the same for co infection.

Other viruses will emerge in the future looking to knock off a few millions of us.  When that occurs, the viral assimilation theory could be useful.  Keep in mind that no virus has ever been successfully cured by man, not one.   Perhaps the primary aim shouldn’t be to ‘cure’ a virus, but rather to encourage and speed up its assimilation.  This is what the current cure for hepatitis C is.  It doesn’t eradicate the virus antibodies from the body, but reduces the viral load, mutates, and teaches the body to live and thrive with it.  It probably doesn’t do those of us living with one or two of the cousins much good right now, but one of our biological directives in living is to add to the knowledge that helps the species to keep on living.   In effect, we are the experiment.  We always have been, and it's likely that aspect of medicine will never go away.

Our race, the human race, has a date with Destiny.  We all sense that.  And Destiny?   He’s all dressed up and ready to go while we’re still pulling on our lacy little underthings.



Larry & LuLu



HIV, HCV and coinfection news

1.  Telaprevir and coinfection.

2.  Coinfection increases chances of bone fractures.

3.  Peregrine Pharmaceuticals advances study of bavituximab.

1. Telaprevir and coinfection

The experimental hepatitis C virus (HCV) protease inhibitor telaprevir, combined with pegyalted interferon plus ribavirin, reduced HCV viral load to undetectable levels in about 70% of HIV positive patients at weeks 4 and 12 in the first study of the drug in HIV/HCV coinfected people. Based on these eagerly awaited Phase 2 results, presented this week at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) in Boston, Vertex Pharmaceuticals plans to start a Phase 3 coinfection study later this year.  GO to the published abstract from the 18th annual CROI report at HIV and Hepatitis.

2. Coinfection increases chances of bone fractures. 

People coinfected with HIV and HCV appear to face an higher risk of bone fractures, according to new data reported Tuesday, July 20, at the XVIII International AIDS Conference in Vienna. Decreased bone mineral density is increasingly reported in the aging HIV-positive population. The risk of fractures has also been found to be increased among people living with HIV, compared with non-HIV-infected patients.  The overall prevalence of fragility fractures—a broken vertebrae, hip or wrist after falling from standing height or less—is higher among women, but men face a greater risk of death associated with fractures and they account for the majority of HIV cases in the United States.  The overall mortality is about 20 percent in the first 12 months after a hip fracture and is higher in men than women.  GO to AidsMeds for the entire report from XVIII International AIDS Conference in Vienna.

3.  Peregrine Pharmaceuticals advances study of bavituximab.

TUSTIN, CA - Peregrine Pharmaceuticals, Inc. a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, announced the completion of enrollment in the company's Phase Ib dose escalation safety study of bavituximab in patients coinfected with chronic HCV and HIV.  Completion of enrollment  and sets the stage for reporting clinical data at a medical conference in the second quarter of this year and beginning to evaluate combination treatment with the antiviral agent ribavirin.  Standard treatment for chronic HCV may soon evolve with the introduction of new targeted antiviral drug candidates, immune stimulation with interferon remains a critical component of therapy. Preclinical data support the potential combination of bavituximab and ribavirin.  In prior HCV clinical trials, bavituximab administered as monotherapy in single and multiple doses demonstrated a positive safety profile with no dose-limiting toxicities or serious adverse events. Bavituximab as a monotherapy also showed promising antiviral activity of up to 1.5 log viral load reduction.  Bavituximab may address a fundamental "immune evasion" mechanism exploited by many infectious pathogens. A growing body of published data from researchers worldwide shows that bavituximab's PS target, exposed on the surface of cells infected by viruses and protozoan parasites, suppresses the immune system's ability to fight disease. PS-targeting antibodies such as bavituximab bind to PS and block the immunosuppressive signals created by the target, thereby allowing the immune system to mount a robust immune response against the pathogen.  GO to Yahoo.

HIV/HCV coinfection update

HIV-HCV Coinfection Update

Sheila Lahijani, BS, RPh
Brown Medical School

Lynn E. Taylor, MD
Assistant Professor of Medicine, Brown Medical School

(condensed and excerpted from a posting in HCV Advocate, Medical Writers Circle)

Link: Coinfection update

Background
Human Immunodeficiency Virus (HIV) and chronic hepatitis C virus (HCV) coinfection is a growing public health concern, with an estimated 4-5 million persons coinfected worldwide.  In the United States, of the approximately one million people living with HIV/AIDS (PLWHA), 30% are also infected with HCV. 

In the late 1990s, with the introduction of potent medication combinations against HIV (highly active antiretroviral therapy, HAART) death rates due to AIDS declined dramatically.  Other medical problems emerged, namely liver disease due to chronic HCV.  … HIV affects the natural course of HCV by accelerating the rate of fibrosis (scarring) progression.  Coinfected persons may develop cirrhosis and end-stage liver disease more quickly.  Liver disease has become a leading cause of death and illness [in] PLWHA with well-controlled HIV.  It is important to acknowledge coinfection as a distinct condition.

DiagnosisAll PLWHA should be screened for HCV. HIV-seropositive persons can have a negative HCV antibody but still be infected with HCV (false negative test). 

There is controversy regarding the role of liver biopsy in HIV-HCV coinfection.  Liver biopsy is not a perfect test.  It is associated with risks, can give inaccurate results, and is not always accessible.  Lack of a liver biopsy should not prevent treatment.  Some experts agree that if a person has a high likelihood of achieving a sustained virologic response (SVR) and/or is a candidate for pegylated interferon/ribavirin therapy, th[ey] should receive HCV treatment without a liver biopsy.  If a coinfected person shows signs of cirrhosis, a liver biopsy is not necessary.

 

When should a repeat biopsy be performed?  Two to three years in the setting of HIV.  It is important to note that ALT levels in the blood do not always reliably indicate the extent of liver disease in HIV-HCV coinfected individuals.  Therefore, ALT should not be used to guide decisions on biopsy or treatment.

 

Evaluation and Treatment
Every HIV-HCV coinfected person with compensated chronic HCV (which means no history of ascites/fluid in the belly, encephalopathy/toxins in the bloodstream due to the liver’s inability to filter, or variceal bleeding/bleeding from swollen veins around the liver) should be considered for HCV antiviral therapy.

 

There is more data available now about the use of pegylated interferon and ribavirin combination therapy in coinfection.  Studies indicated that the optimal first-line treatment for chronic HCV in HIV-seropositive individuals never before treated for HCV is pegylated interferon plus ribavirin.  Even when SVR does not occur, fibrosis in the liver can improve or stabilize.  [The] studies showed that adherence to pegylated interferon and ribavirin is critical to successful therapy; coinfected individuals need to take at least 80% of their ribavirin and 80% of their pegylated interferon doses for at least 80% of the course of therapy in order to get the maximum benefit. 

As most coinfected persons in the U.S. have genotype 1 infection and high HCV viral loads, investigators are considering strategies to boost treatment efficacy.  The best dose of ribavirin and optimal length of treatment are not yet established.  Most large studies have used lower doses (e.g. 800 mg daily) of ribavirin rather than the weight-based higher doses due to concerns about side effects, especially anemia (a drop in red blood cells that carry oxygen). 

The present understanding is that many individuals contending with drug addiction and/or mental health problems can be treated for HCV with multidisciplinary care and appropriate supports.  

Current Recommendations

The only contraindication specific to HIV-seropositive persons is an active opportunistic infection.  Liver enzymes should be monitored after starting HIV medications.  Individuals should be screened for hepatitis A and B and given vaccines for these liver viruses if they are susceptible.  Counseling and education is an important part of care to reduce transmission to others and diminish further liver damage.  All coinfected individuals should be advised to avoid alcohol since it is known to worsen liver disease.  Alcohol also can have a negative influence on treatment response.  Condom use is recommended.  Of recent concern are reports of outbreaks of acute (new) HCV among HIV-positive men who have sex with men, likely due to unprotected anal sex, potentially facilitated by co-occurring sexually transmitted infections. 

Future Directions
Over the last few years much progress has been made in understanding coinfection.  An enormous need for further research remains.  Studies are in progress to evaluate new agents (potential medications) to target the HCV virus.  As the population of coinfected individuals ages, there will be a greater prevalence of advanced liver disease over time.

Drug dependence is among the main reasons that coinfected persons are not being treated for HCV infection.  This does not need to be the case and makes little sense given that the reservoir of HCV infection in the U.S. is among persons who inject drugs.

Finally, prevention efforts are vital to stem the overlapping epidemics of HIV, HCV and opioid addiction, and to limit the burden of liver disease among PLWHA.  These include expanded access to: HCV and HIV testing and care; sterile syringes via needle exchange programs and over-the-counter syringe sales; substance abuse treatment; and integrated, cross-disciplinary HIV, HCV and addiction care.  This can only occur with additional resources.  It is a public health imperative to prevent further coinfection and to expand access to high quality HCV care for PLWHA.