June 26, 2013

The War On Drugs Kills: Support, Don't Punish

Sonal Mehta

Director for Programmes and Policy at India HIV/AIDS Alliance

Posted: 06/26/2013 2:02 pm

For more than 40 years, the international community has waged a misguided war against drug use that has done little more than make illegal drugs a multi-billion dollar global industry and contribute to the deaths of literally millions of drug users. Simply put, the war on drugs kills people who use drugs.

On June 26 each year, the United Nations marks the International Day Against Drug Abuse and Illicit Trafficking. This year, we are making it a day against the abuse of drug users by marking the start of the Support Don't Punish campaign to encourage governments to end the war on drugs that fuels the HIV, tuberculosis and hepatitis epidemics, violates human rights and fails to actually tackle the world's drug problem.

What is it about drugs and drug use that has led to this almost universal disapproval? India is a country of over a billion people, a good number of whom have used drugs in some form at some point in their lives. Are they all criminals? Our government certainly thinks so, as do most of the world's governments. Some even consider drug use a criminal offense punishable by death.

Some drug use has always been part of our social and religious culture but it has only been in the last hundred years or so that we have seen the steady tightening of controls on drugs and drug use. The price of this war however is not simply the cost of enforcement and incarceration.

Globally, the HIV and hepatitis C epidemics are fuelled by the criminalization of people who use drugs. Of the 16 million people who inject drugs worldwide, around three million are living with HIV and two thirds are living with hepatitis C. Even though one third of all HIV infections outside of sub-Saharan Africa are among people who inject drugs and even though the evidence of this is quite clear, the necessary funding for specialist prevention services has not followed.

While HIV prevalence in people who inject drugs is 24 times that of the general population in India, less than 3% of the $820 million invested by the Global Fund here in HIV programming so far supports them. While our friends at the Global Fund understand the value of such investments, it's often difficult for countries to get the political support needed to address HIV risk in the context of drug use due to its criminalization. This dynamic fuels a vicious cycle of neglect.

Criminalization undermines the effectiveness of the HIV response. In India and elsewhere, we need to scale up evidence‐based HIV prevention measures for people who inject drugs. The Support Don't Punish campaign calls for the removal of legal sanctions on low-level drug offenses and for the scale-up of scientifically proven health interventions, including a package of "harm reduction" services fully endorsed by the World Health Organisation, UNAIDS, and the United Nations Office on Drugs and Crime. This includes interventions to prevent the sharing of injecting equipment like needle and syringe exchange and effective programmes for those with drug dependency problems, such as opioid substitution therapy.

Rather than demonizing people who use drugs, we should humanize them. Rather than jailing them, we should get them the treatment they need. Rather than punishing them, we must support them. We need to end the war on drugs and make our priority the wellbeing of people who use drugs, their families and communities.


Lure, variety of designer drugs is alarming, U.N. agency says

By Fredrik Dahl

VIENNA | Wed Jun 26, 2013 4:13am EDT

VIENNA (Reuters) - A sharp rise in the variety of legal "designer drugs" with names that entice young people into thinking they pose no risk is alarming from a public health standpoint, the United Nations drugs agency said on Wednesday.

The number of new psychoactive substances - marketed as "designer drugs" and "legal highs" - as reported by member states jumped by more than 50 percent in less than three years to 251 by mid-2012, the U.N. Office on Drugs and Crime said.

"This is an alarming drug problem - but the drugs are legal," it said. "Sold openly, including via the Internet, NPS (new psychoactive substances), which have not been tested for safety, can be far more dangerous than traditional drugs."

Names including "spice", "meow-meow" and "bath salts" mislead young people into believing they are indulging in low-risk fun, UNODC said.

But "the adverse effects and addictive potential of most of these uncontrolled substances are at best poorly understood", the agency said in an annual survey.

Use of such substances among youth in the United States appears to be more than twice as widespread as in the 27-nation European Union, where the United Kingdom, Poland and France have the most users, it said.

New psychoactive substances can be made by slightly modifying the molecular structure of controlled drugs, making a new drug with similar effects which can elude national and international bans.

They are "proliferating at an unprecedented rate and posing unforeseen public health challenges," said the report that examines production, trafficking and consumption trends.

"The international drug control system is floundering, for the first time, under the speed and creativity of the phenomenon" of this type of substances, the UNODC report said.


Overall, global drug consumption has remained stable, the report said, referring to the number of drug users with dependence or drug-use disorders. In 2011, the number of drug-related deaths was estimated at 211,000.

"While the use of traditional drugs, such as heroin and cocaine, seems to be declining in some parts of the world, prescription drug abuse and new psychoactive substance abuse is growing," it said.

Heroin use in Europe and that of cocaine in the United States appear to be falling while the cocaine market is expanding in South America and the emerging economies in Asia.

The U.N. agency's 2013 World Drug Report also said revised data showed that the prevalence of people injecting drugs who are also infected with the human immunodeficiency virus that causes AIDS was sharply lower than previously estimated.

In 2011, about 1.6 million people between the ages of 15 and 64 who injected drugs were living with HIV, a 46 percent decline since estimates three years earlier. The overall number of people using needles to take drugs was also lower.

The reduced figures are "in large part a result of the availability of more reliable information on HIV prevalence among people who inject drugs", the report said.

Criminals have been quick to tap into the lucrative market of new psychoactive substances while the law lags behind, the U.N. office said. Africa is becoming a target for the trafficking and production of illicit substances, it added.

"East and West Africa seems to be gaining in prominence with regard to routes for maritime trafficking," the report said. Seizures of heroin have risen sharply in Africa since 2009, especially in East Africa, where they increased almost tenfold.

(Editing by Michael Roddy)


Cost-Effectiveness Analysis of Direct-Acting Antiviral Therapy for Treatment-Naïve Patients with Chronic Hepatitis C Genotype 1 Infection in the Veterans Health Administration

Provided by NATAP

Download the PDF

Clinical Gastroenterology and Hepatology June 2013
Article in Press

HCV Care in VA Debated - (06/24/13)

Kee Chan, PhD1,2,3, Mai Ngan Lai, MD4, Erik J. Groessl, PhD4,5, Amresh D. Hanchate, PhD3,6, John B. Wong, MD 7, Jack A. Clark, PhD 3,6, Steven M. Asch, MD MPH8, Allen L. Gifford, MD3,6, and Samuel B. Ho, MD 4,5

1. Department of Health Sciences, College of Health and Rehabilitation Sciences: Sargent College, Boston University, Boston, MA
2. Department of Epidemiology, School of Public Health, Boston University, Boston, MA
3. VA HIV/Hepatitis Quality Enhancement Research Initiative, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA
4. VA San Diego Healthcare System, San Diego, CA
5. University of California, San Diego, San Diego, CA
6. Departments of Health Policy and Management, and Medicine, Boston University, Boston, MA
7. Division of Clinical Decision Making, Informatics, and Telemedicine, Tufts Medical Center, Boston, MA
8. HRS&D Center of Excellence and Research Service, VA Palo Alto Healthcare System, Palo Alto, CA

"In conclusion, our model indicates the upfront costs required for treatment with Boc/PR or Tel/PR are high; however the offsetting benefits of extending quality of life and lower costs due to liver-related morbidity indicate that these therapies have very acceptable incremental cost-effectiveness ratios compared to previous therapies in this managed care health care system. Further efforts to expand access to DAA therapy are warranted. In our study, we evaluated cost effectiveness of DAA treatment strategies in a defined managed care population with pharmaceutical pricing based on large group negotiated prices. In the future, integrated care systems may be more common with the evolution of the Affordable Care Act and similar heath care reforms38, and drug pricing advantages will play an important role in determining overall cost effectiveness of new medications. In addition, our data is more relevant to health care systems in other countries with similar large group negotiated prices.

Cost-effectiveness ratios are one very important, but not sufficient, factor for making health policy decisions. Other factors such as system adaptability, budgetary issues, and patient preferences should also be considered in addition to our findings. This model will continue to be of use to evaluate future DAA therapies for HCV treatment, which may demonstrate increased efficacy albeit with significant costs."

Background and Aim

The Veterans Health Administration (VHA) is the largest single provider of care for hepatitis C virus (HCV) infection in the US. We analyzed the cost-effectiveness of treatment with the HCV protease inhibitors boceprevir and telaprevir in a defined managed care population of 102,851 patients with untreated chronic genotype 1 infection.


We used a decision-analytic Markov model to examine 4 strategies: standard dual-therapy with pegylated interferon-alfa and ribavirin (PR), the combination of boceprevir and PR triple therapy, the combination of telaprevir and PR, or no antiviral treatment; sensitivity analysis was performed. Sources of data included published rates of disease progression, the census bureau, and VHA pharmacy and hospitalization cost databases.


The estimated costs for treating each patient were $8000 for PR, $31,300 for boceprevier and PR, and $41,700 for telaprevir and PR. Assuming VHA treatment rates of 22% and optimal rates of sustained viral response, PR, boceprevir and PR, and telaprevir and PR would reduce relative liver-related deaths by 5.2%, 10.9%, and 11.5%, respectively. Increasing treatment rates to 50% would reduce liver-related deaths by 12%, 24.7%, and 26.1%, respectively. The incremental cost-effectiveness ratios were $29,184/quality of adjusted-life years (QALY) for boceprevir and PR and $44,247/QALY for telaprevir and PR vs only PR. With the current 22% treatment rate, total system-wide costs to adopt boceprevir and PR or telaprevir and PR would range from $708 million to $943 million.


Despite substantial upfront costs of treating HCV-infected patients in the VHA with PR, or telaprevir and PR, each regimen improves quality of life and extends life expectancy, by reducing liver-related morbidity and mortality, and should be cost effective. Further efforts to expand access to direct-acting antiviral therapy are warranted.



Compared to no treatment, use of standard PR therapy in the patient population at the treatment rate of 22% previously achieved among VA patients initiated on antiviral therapy between 2000-20081, 19 will decrease overall liver-related mortality by 5.0% (Table 2 and Figure 2). In contrast, treatment with DAA triple therapies at this same treatment rate, assuming the highest expected SVR rates (Boc/PR 54 % and Tel/PR 57%), will result in a 10.4 to 11.0% reduction in liver related death, respectively. If a treatment rates with PR, Boc/PR or Tel/PR can be increased to 50% of patients, the long-term reduction liver-related deaths will be 11.4%, 23.7% and 25.0%, respectively.

Cost and cost-effectiveness of antiviral treatments

With the previously achieved inital treatment rate of 22 %, total system-wide costs to adopt Boc/PR or Tel/PR would be $708 million and $943 million, respectively. Increasing treatment rates to 50% would result in the total cost of antiviral therapies PR, Boc/PR and Tel/PR treatment to be $411 million, $1,610 million and $2,144 million, respectively (Figure 3). Without antiviral treatment, the expected total cost of care for hepatitis C-related liver disease is $3,729 million. Compared with no treatment using PR at a 50% treatment rate results in overall cost savings of $30 million over the VHA cohort lifetime. In contrast, using Boc/PR or Tel/PR at a 50% treatment rate results in net cost expenditures of $692 million or $1,175 million, respectively.

The estimated cost and effectiveness (QALY) for the average treatment-naïve genotype 1 VHA patient and the incremental cost effectiveness ratio of DAA triple therapies compared with no therapy and PR therapy are given in Table 3A. Assuming the higher estimated SVR rates, the ICER for BocPR vs. PR = $29,184/QALY gained and TelPR vs. PR = $44,247/QALY gained.

Erythropoetin use was considered optional in the Boc licensing trial and not used in Tel licensing trials, and no SVR data is available for patients treated with TelPR when erythropoietin is used. Table 3B demonstrates the changes in ICER for DAA and PR therapies if potential costs of erythropoietin are included, which is common in clinical practice, although not universal.

For comparison purposes, the corresponding ICERs calculated using the average wholesale prices for Ribavirin, Peginterferon alfa, Boceprevir and Telaprevir are listed in Supplemental Table 6. The cost effectiveness for the four treatment strategies based on patient age and fibrosis stage are listed in Supplemental Table 7, and indicate that treating subgroups with younger age and more advanced fibrosis stage will be more cost-effective. As of 2010 there were approximately 21,466 genotype 1 patients that failed previous interferon treatment in the VHA. There is little data available concerning treatment of prior PR treatment failures in VHA populations, therefore we have used data from published phase III trials to make preliminary estimates related to incremental cost effectiveness ratios of DAA re-treatment in this patient population (Technical Appendix and Supplemental Table 8) 14, 15, 32


Our model projects cost-effectiveness analysis of the new DAAs therapy in the veteran population. Our simulated cohort of 102,851 treatment-naïve US veteran patients with HCV genotype 1 infection had more than 2-fold reduction in liver related death when they were treated with either Boc/PR or Tel/PR strategies compared to treatment with PR alone. When we used VHA contract FSS pricing, the incremental cost effectiveness ratio (ICER) of Boc/PR and Tel/PR compared with PR are $29,184/QALY gained and $44,247/QALY gained, respectively. The ICER of Boc/PR and Tel/PR compared to no treatment are $15,027/QALY gained and $24,467/QALY gained, respectively. For patients in their 40's and 50's with early fibrosis stage 1 and 2, the ICERs for DAA treatments compared with PR are within the oft cited $50,000/QALY gained threshold for consideration of acceptable ICERs for medical interventions. Our results indicate that these therapies are cost-effective for the majority of US veteran patients.

Other recent studies have showed similar cost-effectiveness results using wholesale pricing of the new DAA therapy. Liu et al. used average wholesale pricing for DAA therapy of $1100 per week 33. They projected the ICER of triple therapy vs. dual therapy would be $102,600 for patients with mild fibrosis and $51,000 for patients with advanced fibrosis, which is considerably higher than our projected cost effectiveness as would be expected given their higher pharmaceutical costs. Strategies to improve the ICERs of HCV antiviral treatments in the community setting may include selecting patients (such as those with advanced fibrosis) who would be more likely to benefit from therapy. In addition, they evaluated the use of the strategy of IL28 genotyping to guide therapy, with IL28 CC genotypes receiving PR therapy first. IL28-guided triple therapy treatment strategy results in reduced ICER for triple therapy treatment, although reductions in lifetime decompensated cirrhosis and HCC obtained with this strategy were only approximately 83% of those achieved with universal triple therapy. Recent data has demonstrated that IL28 CC patients treated with Tel/PR for 12 weeks achieve a 100% SVR rate compared with 64% SVR for these patients treated with PR for 48 weeks34. These data appear to mitigate the benefits of an IL28-guided strategy and lessen the likelihood that this would be an acceptable clinical alternative, yet further efforts to select patients most likely to benefit would be warranted under these scenarios. Further comparisons and limitations of our study are listed in the Technical Appendix.

We accounted for uncertainties regarding DAA treatment by estimating a range of possible SVR rates based on SVR rates attained in the VHA population with dual therapy pegylated interferon alfa and ribavirin. A recent meta-analysis by Cooper et al. compared SVR rates of BocPR and TelPR based on all data from phase II and phase III trials using a network meta-analysis and indirect comparisons to relative risk for SVR, and resulted in similar results as our analysis using phase III trial data35. For estimating duration of therapy with DAA treatments we used data from registration trials to calculate the percentage of patients with early treatment discontinuation and the percentage eligible to receive shorter durations of therapy. Because data from the Boceprevir registration trial was reported for Non-black and Black populations separately, we adjusted the treatment duration estimates for the known Non-black and Black patient distribution in VHA HCV patients, and therefore this data may be more accurate than the estimated treatment durations obtained from the Telaprevir registration trial.

A critical question for health care systems is the percentage of patients that are able to receive current antiviral therapies. Our data reflects the optimistic treatment rate of 50%, with the potential consequence of a 24-25% reduction in liver-related deaths. Such treatment rates in a VHA population may be attained with the use of integrated care protocols, which have surpassed 40% of VHA patients with pre-existing risk factors for psychiatric and substance use conditions in a recent study36, 37. Future interferon-free regimens are likely necessary for maximizing the number of HCV patients that can receive antiviral therapy.

In conclusion, our model indicates the upfront costs required for treatment with Boc/PR or Tel/PR are high; however the offsetting benefits of extending quality of life and lower costs due to liver-related morbidity indicate that these therapies have very acceptable incremental cost-effectiveness ratios compared to previous therapies in this managed care health care system. Further efforts to expand access to DAA therapy are warranted. In our study, we evaluated cost effectiveness of DAA treatment strategies in a defined managed care population with pharmaceutical pricing based on large group negotiated prices. In the future, integrated care systems may be more common with the evolution of the Affordable Care Act and similar heath care reforms38, and drug pricing advantages will play an important role in determining overall cost effectiveness of new medications. In addition, our data is more relevant to health care systems in other countries with similar large group negotiated prices.

Cost-effectiveness ratios are one very important, but not sufficient, factor for making health policy decisions. Other factors such as system adaptability, budgetary issues, and patient preferences should also be considered in addition to our findings. This model will continue to be of use to evaluate future DAA therapies for HCV treatment, which may demonstrate increased efficacy albeit with significant costs.


Drug-Induced Liver Injury Is On the Rise

Provided by the American Gastroenterological Association

Bethesda, MD (June 26, 2013) — More people are being affected by drug-induced liver injury (DILI) than ever before, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association. This type of liver injury results from the use of certain prescription and over-the-counter medications, as well as dietary supplements, and is among the more challenging forms of liver disease due to its difficulty to predict, diagnose and manage.

Investigators conducted a population-based study in Iceland uncovering 19.1 cases of drug-induced liver injury per 100,000 inhabitants, per year. These results are significantly higher than the last population-based study of this kind, conducted in France from 1997-2000, which reported 13.9 cases per 100,000 inhabitants, per year.

The most commonly implicated drugs were amoxicillin-clavulante (penicillin used to fight bacteria), azathioprine (an immunosuppressive drug used in organ transplantation and autoimmune diseases) and infliximab (also used to treat autoimmune disease).

“Drug-induced liver injury is not a single, uncommon disease of the general population, but rather a series of rare diseases that occur only in persons who take specific medications,” said Einar S. Björnsson, lead study author from the department of internal medicine, section of gastroenterology and hepatology, National University Hospital, Reykjavik, Iceland, and faculty of medicine at the University of Iceland. “Our study identified which medications put patients most at risk for developing liver diseases. With this information, physicians can better monitor and manage patients who are prescribed potentially liver-injuring drugs.”

The study also showed that drug-induced liver injury was caused by a single prescription medication in 75 percent of cases, by dietary supplements in 16 percent and by multiple agents in 9 percent. Further, the incidence was similar in women and men, but increased with age; not surprising since the need for medication also increases with age.

Jaundice and other symptoms highly suggestive of liver injury, such as itching, nausea, abdominal discomfort and lethargy, were present in the majority of patients. Most patients had a favorable outcome after receiving care.

For more, watch Dr. Björnsson discuss his research in a Gastroenterology video abstract.

About the AGA Institute

The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to include 17,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. www.gastro.org.

About Gastroenterology 

Gastroenterology, the official journal of the AGA Institute, is the most prominent scientific journal in the specialty and is in the top 1 percent of indexed medical journals internationally. The journal publishes clinical and basic science studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. The journal is abstracted and indexed in Biological Abstracts, Current Awareness in Biological Sciences, Chemical Abstracts, Current Contents, Excerpta Medica, Index Medicus, Nutrition Abstracts and Science Citation Index. For more information, visit www.gastrojournal.org.

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Meta-analysis linked NAFLD, vitamin D deficiency

Provided by Healio

Eliades M. Aliment Pharmacol Ther. 2013;doi:10.1111/apt.12377.

June 26, 2013

Vitamin D deficiency may be linked to the development of nonalcoholic fatty liver disease, according to a recent study.

Researchers performed a systematic review of 17 case-control and cross-sectional studies, assessing the association between nonalcoholic fatty liver disease (NAFLD) and serum levels of 25-hydroxy vitamin D (25[OH]D). Included studies were selected from PubMed and EMBASE databases and published before April 22, 2013, evaluated vitamin D levels among cases and controls, and were based in North America (six studies), Asia (four studies) and Europe or Israel (seven studies).

Most studies indicated that vitamin D deficiency was more prevalent among patients with NAFLD than controls. This association lost statistical significance after adjustment for confounders in two studies, and two studies indicated an inverse association between NAFLD, as indicated independently by ALT and vitamin D levels.

Investigators also conducted a pooled analysis including 11 studies, with nine assessing continuous vitamin D levels in 4,855 patients and 7,939 controls, and nine assessing categorical vitamin D in 5,202 patients and 8,520 controls.

Analysis of continuous vitamin D indicated that those with NAFLD had average 25(OH)D levels 0.36 ng/mL lower than controls (P<.01). Assessment of categorical vitamin D indicated that patients with NAFLD were 26% more likely than controls to be vitamin D-deficient (OR=1.26; 95% CI, 1.17-1.35). Deficiency was more prevalent and more severe among Western participants with NAFLD than Eastern patients. Results were not impacted by the exclusion of individual studies, and no evidence of publication bias was observed (P=.32).

“We have demonstrated that vitamin D deficiency is prevalent in NAFLD subjects, suggesting that vitamin D may play a role in the development of the disease,” the researchers concluded. “The anti-inflammatory and immune-modulatory properties of vitamin D provide plausible mechanisms by which vitamin D may impact on disease progression and severity in NAFLD.

“Future research should focus on investigating prospectively the association between vitamin D and NAFLD, as well as on randomized controlled trials of vitamin D supplementation in NAFLD subjects.”


A Genetic Biomarker for Long-Term Prognosis of HCV-Related Cirrhosis

June 20, 2013

Atif Zaman, MD, MPH reviewing Hoshida Y et al. Gastroenterology 2013 May.

Profiling a 186-gene signature from needle-biopsy specimens could improve targeting of intensive surveillance to the highest-risk patients.

Hepatitis C virus (HCV)–related cirrhosis is a leading cause of liver-related morbidity and mortality. Identifying prognostic biomarkers of long-term outcomes might allow clinicians to risk-stratify their patients with cirrhosis and target high-risk patients for closer, more-intensive monitoring. In the current study, investigators assessed whether a 186-gene signature from liver tissue can predict death, progression of cirrhosis, or hepatocellular carcinoma (HCC) in HCV-infected patients with cirrhosis.

Researchers performed whole-genome gene expression profiling on archived liver biopsy tissue of 216 HCV-infected patients with Child-Pugh Class A cirrhosis (identified only by histology). The patients had been enrolled in a long-term, cohort study between 1985 and 1998 (N Engl J Med 1991; 325:675). During median follow-up of 10 years, 66 patients died (31%; 28 from HCC, 20 from liver failure, and 15 from non-liver–related causes), 71 (34%) developed hepatic decompensation, 66 (31%) progressed to Child-Pugh class B or C, 65 (30%) developed HCC (annual incidence, 2.9%), and 12 patients underwent liver transplantation.

Using the gene expression signature, patients were categorized by prognosis: poor (25%); intermediate (47%), or good (28%). In multivariate analysis, having a poor-prognosis signature was significantly associated with increased risk for death (P=0.004), liver disease progression (P<0.001), and HCC development (P=0.009). In the poor-, intermediate-, and good-prognosis groups, 10-year survival rates were 63%, 74%, and 85%, respectively, and annual HCC incidence rates were 5.8%, 2.2%, and 1.5%.


This study has significant clinical implications. First, such prognostic data will allow clinicians to advise patients with hepatitis C virus and early cirrhosis on their long-term prognoses. Second, these data will enable clinicians and public health programs to more appropriately target intensive surveillance practices to high-risk patients. Finally, genome-wide profiling can seemingly be performed on needle-biopsy specimens, thus allowing these important data to be gathered during routine clinical care. Once this 186-gene signature is further validated, it will become an important clinical tool.

Disclosures for Atif Zaman, MD, MPH at time of publication Speaker&#8217;s bureau Bristol-Myers Squibb; Genentech; Gilead; Kadmon; Merck; Salix; Vertex


Hoshida Y et al. Prognostic gene expression signature for patients with hepatitis C–related early-stage cirrhosis. Gastroenterology 2013 May; 144:1024. (http://dx.doi.org/10.1053/j.gastro.2013.01.021)

PubMed abstract (Free)