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.