Tuesday, February 05, 2013

GSK - ViiV Abandons Lersivirine - An Investigational NNRTI HIV Medication



Dear HIV Community Writer,

ViiV Healthcare has taken the decision to stop the development program investigating the non-nucleoside reverse transcriptase inhibitor (NNRTI), lersivirine.  This is not due to any safety concerns regarding the compound. ViiV Healthcare’s goal is to support the best possible outcomes for people living with HIV, and to deliver new therapies that offer improvement over current options. 

After much deliberation about how to proceed with lersivirine, it was determined that the compound would not provide an improvement over existing medicines in the NNRTI class, and that R&D resources for ViiV Healthcare should prioritize efforts to identify compounds that further HIV treatment.

We remain committed to exploring candidates that will advance HIV treatment and contribute to improving outcomes for people living with HIV.

Please don’t hesitate to reach out to me directly if you have any questions regarding this announcement.

Kind regards,



Marc Meachem | Director, External Affairs

Monday, February 04, 2013

Successful treatment is "as effective as consistent condom use" in reducing HIV transmission


At least, for vaginal sex...(no data on anal sex!)

The statement notes that there is now conclusive randomised clinical trial evidence, from the HPTN 052 trial, to show that transmission of HIV through vaginal sex is significantly reduced when an HIV-positive person is taking effective antiretroviral therapy (ART). In this trial, early treatment reduced HIV transmission to an uninfected partner by 96%.


Position statement on the use of antiretroviral therapy to reduce HIV transmission January 2013. The British HIV Association (BHIVA) and the Expert Advisory Group on AIDS

Recent Studies Show Concerns With The Use of Tenofovir (Viread), Popular Drug in HIV Treatment



Tenofovir impairs enzyme that stops cells aging


This study let us know that NRTI drugs, already known for causing the damage to mitochondrial DNA that leads to peripheral neuropathy, fat loss and some other side-effects, also exert an effect on cellular DNA, and that in this case tenofovir may be the drug to keep an eye on.

Telomerase shortening is, by definition, a side-effect that won’t start causing symptoms for many years, and the study does provide a cautionary note in discussions about the possibility of very long-term side-effects associated with the use of tenofovir, both in HIV treatment and in pre-exposure prophylaxis.

More information here


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Changes in Fat Mitochondrial DNA and Function in Subjects Randomized to Abacavir+Lamivudine or Tenofovir DF+ Emtricitabine With Atazanavir-Ritonavir or Efavirenz: AIDS Clinical Trials Group Study A5224s, Substudy of A5202


"In conclusion, we have shown significant perturbation in mitochondrial indices after 96 weeks of nonthymidine NRTI containing regimens which were assigned randomly. In the TDF/FTC group, changes in oxidative phosphorylation complex I and complex IV activity levels consistently were inversely correlated with changes in several objective measures of body fat, including in both subcutaneous and visceral compartments"


  Patients with human immunodeficiency virus type 1 (HIV-1) infection receiving thymidine nucleoside reverse-transcriptase inhibitors (NRTIs) experience a high rate of metabolic abnormalities, including lipoatrophy. Depletion of adipose tissue mitochondrial DNA (mtDNA) and impairment of the oxidative phosphorylation system are associated with lipoatrophy induced by thymidine NRTI containing regimens. Mitochondrial oxidative phosphorylation enzymes nicotinamide adenine dinucleotide (reduced; NADH) dehydrogenase (complex I) and cytochrome c oxidase (complex IV) contain polypeptides of mtDNA-encoded subunits and so are affected by mtDNA depletion.
In the current era of nonthymidine NRTI containing regimens, lipoatrophy incidence has significantly decreased but has not been completely prevented . In addition, subjects who have established lipoatrophy while taking thymidine NRTI containing regimens experience only a slow and incomplete resolution of lipoatrophy after switching to nonthymidine NRTI based therapy , putting into question the mitochondrial toxicity.

More information here

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Fortunately, 10 year observational data on the use of TDF show encouraging results in stabilization of reduced creatinine clearance


Association Between Tenofovir Exposure and Reduced Kidney Function in a Cohort of HIV-Positive Patients: Results From 10 Years of Follow-up


 "In this cohort, TDF exposure was associated with reduced kidney function, but the loss in eGFR attributable to TDF is relatively mild in a long-term perspective.

There has been debate about the association between TDF exposure and renal dysfunction and about the clinical impact of the loss in eGFR due to TDF exposure. Our study shows that the association was not of a high magnitude and that the quantified loss in eGFR attributable to TDF is relatively modest after many years of exposure. Importantly, the loss attributable to TDF seems to occur during the first year of exposure and stabilizes after that. Although the loss is maintained, it does not seem to further deteriorate with additional years of exposure. The clinical impact of this association need to be analyzed, taking into account the efficacy of TDF, but it is highly plausible that TDF exposure, although associated with reduced kidney function, has no severe adverse effects over the long term for most HIV-positive patients.”

More information here

Thursday, December 27, 2012

Two companies have an effective 100% cure for Hepatitis C without interferon or ribavirin. But this cure is literally being withheld from millions



Two companies have an effective 100% cure for Hepatitis C without interferon or ribavirin.  But this cure is literally being withheld from millions by pharmaceutical giant Gilead Sciences because they are more concerned about profits than human lives.
This cure is a combination Bristol-Myers Squibb's drug daclatasvir and Gilead Science's GS-7977 (sofosbuvir). When these two drugs were used together, 100 percent of Hepatitis C patients were cured.  These results are amazing for the approximately 170 million people in the world with Hepatitis C.  The problem is that Gilead Sciences is unwilling to work with Bristol-Myers. The cure exists while people continue to suffer and die.
 Dr. Douglas J. Manion, a senior vice president for Bristol-Myers, said his company was "keen" on working with Gilead but that "thus far, they have been unwilling to engage in that collaboration."
Quote from Dr. Paul Thuluvath - Wall Street Journal:
"We had never, ever imagined—even in our wildest dreams—we could treat" hepatitis C so quickly, effectively and without serious side effects, said Paul Thuluvath, a doctor at Mercy Medical Center in Baltimore who had six patients test the new treatment. "I think the pharmaceutical companies have a moral responsibility to work together and bring it to market instead of [following] their own vested interests." 
Quote from Dr. Scott Friedman – New York Times:
“The only appropriate motivation should be what is the best and fastest way to get cures, not what is best for the shareholders,” said Dr. Scott Friedman, chief of liver diseases at the Mount Sinai School of Medicine in New York, who was not involved in the trial.” 
Quote from EASL Secretary General Mark Thursz:
EASL Secretary General Mark Thursz wants to see the two companies work together.
"The combination of daclatasvir and GS-7977 has shown positive results at Phase II. EASL is disappointed that development of this combination has been halted as daclatasvir and GS-7977 promised to deliver a highly effective oral regimen that we hoped would be available to HCV patients soon," said Thursz.
Act NOW and sign the petition to insist Gilead Sciences work with Bristol-Myers on the Phase III drug trials necessary to get this cure to market.   
www.HepC-Cured.org
More than 240,000 people have died since these results were released this past April and there is still no collaboration. How many more must die before Gilead Sciences starts putting human lives before profits?


To:
Gilead Sciences
Gilead Sciences
Gilead Sciences
Bristol-Myers Squibb, Media
John C. Martin, Gilead Sciences, CEO 
Open Letter to Gilead Sciences, their Board of Directors and shareholders:

The recent data from the Boston AASLD meeting confirmed the amazing 100% cure rate with Gilead’s sofosbuvir and Bristol-Myers Squibb’s daclatasvir. Not only did this combination cure genotypes 1, 2 and 3, this cure was achieved without the toxic and debilitating side effects of ribavirin which is known to cause severe anemia and other life-threatening conditions. There are even some concerns that ribavirin may in fact be carcinogenic (see http://www.aafp.org/afp/2005/0815/p655.html) So millions of patients and their families were so very hopeful about the possibility of quick access to this safer and effective HCV drug combination without ribavirin.

But to our continued disbelief and monumental heartbreak, Gilead refuses to move forward in this collaboration with Bristol-Myers Squibb and the most significant discovery in the history of hepatitis C. The rationale for this appears to be nothing more than Gilead’s determination to corner the market with its own in-house NS5a inhibitor GS-5885, which is not effective in the three genotypes and most likely will require the addition of the dreadful ribavirin. Other companies, such as Abbott, are now seeking their own ribavirin-free cocktails and hopefully will prove successful… but it will take years. In the meantime, Gilead could be forging ahead with this combination of sofosbuvir and daclatasvir and bring it to market much sooner than any others in development and start recouping its $11 billion investment as well as saving millions of lives. This would be a win-win situation for everyone involved, i.e., Gilead Sciences, its shareholders, the people suffering and dying with this disease, as well as their families who love them just as much as you love your own families.

Although we may not have hundreds of thousands of signatures on our petition and we have not yet been able to capture the world’s attention about this urgent and dire situation, do not take that as any indication of our intent to quit in the pursuit of this cure. We have no other choice in this matter and we will continue on… day after day, week after week, month after month… until we no longer have any life left in our bodies, or until another company comes up with a cure as safe and effective as this is.


Sincerely,
[Your name]


Here is the petition: 
-http://www.change.org/petitions/gilead-sciences-stop-withholding-this-cure-for-hepatitis-c

HCV Treatment Pipeline Update



Great summary of the research/development pipeline for new Hep C drugs.  It does not include side effects, however.

http://www.pipelinereport.org/toc/HCV/dec-treatment-pipeline-update

Saturday, December 22, 2012

Groundbreaking Gene Therapy Study Gets The Go-Ahead By The FDA




Calimmune, a small biotechnology company, is  giving people a low dose chemo agent (as conditioning) and then infusing them with stem cells  that have been modified to inhibit the CCR5 receptor and to contain their own built-in HIV fusion inhibitor peptide, thereby blocking two sites that are essential for HIV infection.  

The study is enrolling only for HIV+ people who have an R5 virus and who are not taking HIV medications due to their own choice (side effects, etc) for at least 6 weeks. Over 500 CD4 cells required.  Very promising approach  by Calimmune!

An Adaptive Phase I/II Study of the Safety of CD4+ T Lymphocytes and CD34+ Hematopoietic Stem/Progenitor Cells Transduced With LVsh5/C46, a Dual Anti-HIV Gene Transfer Construct, With and Without Conditioning With Busulfan in HIV-1 Infected Adults Previously Exposed to ART


This is the Los Angeles investigator. San Francisco also has a site but it has been fully enrolled

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