Tag Archive: HIV

MOSCOW, Feb 10 (Reuters) – Activists have asked the UN human rights

chief to pressure Russia to legalise the heroin substitute methadone when she visits next week amid a worsening HIV/AIDS crisis, an international health group said on Thursday.

UN High Commissioner for Human Rights Navi Pillay will meet President Dmitry Medvedev, government officials and around 60 rights campaigners during a five-day visit to Moscow.

‚This is a national health crisis and a human rights priority in Russia that must be raised at the highest levels,‘ said senior human rights analyst Damon Barrett from the London-based International Harm Reduction Association (IHRA).

The IHRA and 16 other HIV-focused rights organisations have sent a letter to Pillay asking her to push for HIV/AIDS and drug-fighting measures including the introduction of methadone, during her meetings with Russian government.

The UN’s World Health Organisation (WHO) says Russia has one of the fastest growing HIV/AIDS epidemics in the world, fueled up to three million heroin addicts, many of whom use dirty needles, local health organisations say.

Unlike most countries, Russia refuses to finance harm reduction programmes such as needle exchanges, or to legalise the replacement drug methadone.

The Health Ministry says there is no proof methadone is effective, while the country’s top doctor Gennady Onishchenko has called methadone ‚just another narcotic‘.

‚The fact that the government’s policy is so incomprehensible is what makes it so frustrating,‘ Barrett said.

The WHO says there are a million HIV-positive people in Russia, and deems methadone essential in fighting the epidemic.

Pillay will meet Russian activist Irina Teplinskaya during her visit, said the Moscow-based Andrey Rylkov Foundation, for whom Teplinskaya volunteers. HIV-positive and a heroin user, Teplinskaya has become a symbol of Russia’s drug woes.

‚Because there is no opioid substitution therapy in Russia, drug-dependent people are not able to receive treatment for HIV… they are forced to spend whole days acquiring money in a criminal way so they can buy drugs,‘ Teplinskaya said in a speech she will deliver to Pillay on Sunday.

((For a special report on Russia’s heroin and HIV/AIDS problem: ))

Very interesting Study,

with a Spanish- English Translation

give it a read: drug-use-and-antiretroviral-adherence-in-EN

MOSCOW — They look like addicts anywhere in the world: tattered and vacant-eyed, they circle Moscow pharmacies known to sell prescription drugs illicitly, looking for something to inject for a quick high.

James Hill for The New York Times

Pyotr Nikitenko, right, distributed medical supplies and literature outside a pharmacy in Moscow with a drug outreach center colleague, left. Mr. Nikitenko, a former heroin user, said most of his friends were now H.I.V. positive.

Though public examples of Russia’s problem with heroin are not new and seldom bring even raised eyebrows among locals, the issue has recently come to symbolize a broader failure. The country has become one of the world’s low points in the effort to fight the spread of H.I.V., and unchecked intravenous drug use is the biggest cause, international health officials say.

The epidemic here has defied worldwide trends, expanding more rapidly year by year than almost anywhere else. Nearly 60,000 new cases of H.I.V., the virus that causes AIDS, were documented in Russia in 2009, an 8 percent increase from 2008, according to Unaids, the United Nations H.I.V./AIDS program. Of those new cases, more than 60 percent were believed to have been caused by intravenous drug use, and many of the others were believed to have been infected through sex with addicts.

Though South Africa, with more infections than any other country, far outstripped that total number, with an estimated 390,000 new infections in 2009, the rate of new infections annually has decreased there by nearly half since its peak in the late 1990s.

“I’ve been researching the problem of H.I.V. infection for 25 years, and I must say that the situation has become significantly worse” in Russia, said Dr. Vadim V. Pokrovsky, the head of the country’s Federal AIDS Center.

While in recent years the government has increased its efforts to fight the disease, Dr. Pokrovsky said, current programs almost completely neglect those groups at the heart of it.

Officials estimate that well over a million people abuse drugs intravenously in Russia, often sharing and infecting one another with tainted needles. They are among Russian society’s most marginalized people, more likely to face a few weeks handcuffed to a clinic bed than to receive basic treatment to break their addictions. Meanwhile, officials have treated sex education and other preventative programs with open hostility.

“Which are the main infected groups? Injecting-drug users and sex workers,” said Lev Zohrabyan, the Europe and Central Asia adviser for Unaids. “It turns out that these are the groups where the money must be directed to change the picture. But if you open the budget, you will see that for prevention work among these groups for the next two years there is nothing.”

Top officials have consistently blamed the United States’ failure to eradicate heroin production in Afghanistan for Russia’s intravenous drug problem. About 90 percent of Russian addicts use Afghan heroin, according to the Federal Drug Control Service.

Yet once the drugs pass through Russia’s porous borders with former Soviet republics in Central Asia, dealers find a ready market of addicts with few tools to help them quit. While some regions have experimented with needle-exchange programs, the practice, which has proven effective at reducing the spread of H.I.V. in other countries, has not been adopted on a national level.

The country’s top medical and political officials have roundly condemned drug substitution therapy for heroin addicts — the use of methadone or other narcotics, widely considered an effective way to wean people off the drug — on the basis that it substitutes one form of addiction for another. Doctors who have flouted the official ban on the treatment have faced prosecution and even harassment by Kremlin-backed youth groups.

The Russian Orthodox Church, which has become a significant voice in the country’s political affairs in the past decade, has also expressed strong opposition to such preventative measures.

Even a new antinarcotics strategy ordered by President Dmitri A. Medvedev last summer acknowledges Russia’s failure to adequately confront the problem. “Prophylactic activities, medical aid and rehabilitation of patients with drug addiction are not sufficiently effective,” said the document, posted on Mr. Medvedev’s Web site.

Many of the addicts gathered outside one pharmacy in southern Moscow said they had often tried to stop. “You want to quit, and you don’t,” said a graying 33-year-old named Maxim who had the scarred arms of a dedicated user. Another man, who had quarter-size holes gouged into his body from injection-related infections and would not give his name, said he feared that he would be arrested if he sought treatment — a worry that is not completely unfounded here.

The police often arrest drug users, sending them to special detoxification centers where doctors encourage, and sometimes force, immediate abstinence, which can in some rare cases be fatal. Last summer, organizers of the 18th annual International AIDS Conference held in Vienna issued a declaration — aimed at Russia and the countries of the former Soviet Union, in particular — arguing that such practices drove addicts underground, complicating H.I.V.-prevention efforts.

It is not that the government has failed completely to recognize the gravity of the epidemic. Russia’s national security strategy, approved by Mr. Medvedev, identifies the spread of H.I.V. and AIDS as “one of the main threats to national security in the sphere of medicine and health.”

Russia now has more than 500,000 officially registered cases of H.I.V., though Unaids and other experts have estimated the actual number to be closer to one million, as many as in the United States, which has more than twice the population.

Part of the problem is that the government came late to the fight. The epidemic has been raging since the Soviet collapse two decades ago, but a major government response came only in 2006 when Russia’s obligations as host of the Group of 8 summit meeting pushed officials to take a more active role in fighting the disease. Vladimir V. Putin, who was president at the time and is now prime minister, ordered the largest increase in financing in any area in Russia’s history, and spending has grown annually ever since.

This year, the government plans to nearly double spending on H.I.V. drugs to about $600 million and expand prevention programs focusing on youth, said Galina G. Chistyakova, a Health Ministry official who helps oversee Russia’s H.I.V. and AIDS policies. She denied that Russia was having trouble curbing the epidemic, noting that the ministry had documented a slight dip in the number of new infections in 2010 compared with a year earlier.

Dr. Pokrovsky and others said that government programs often became ensnared in Russia’s large and inefficient bureaucracies. Even efforts to provide AIDS patients with treatment, which constitute the bulk of government financing, have fallen short.

Patients and doctors have complained of frequent shortages of antiretroviral drugs to the point where patients have created online communities, like pereboi.ru, that monitor drug deficits and help those in need of medicines connect with people who have extra supplies. Patients have also held street protests, and others have sued.

Many addicts who become infected do not even know that medicines are available, said Pyotr Nikitenko, 28, a former heroin user who now works for a Moscow-based outreach group called Yasen. He said he was able to wean himself off heroin with the help of his family, escaping the fate of most of his friends, who he said now were H.I.V. positive.

“I continue to bury them,” Mr. Nikitenko said. “They continue to die from AIDS, or rather they are dying more and more frequently.”

What Britain could learn from Portugal’s drugs policy

A decade ago Portugal took a radical new approach to illegal drugs by treating users as people with social problems rather than as criminals. Could it work in the UK?

  • A cannabis smoker in Porto, Portulgal, during a march in favour of legalising drugs
  • A cannabis smoker in Porto, Portugal, during a march in favour of legalising drugs Photograph: Estela Silva/EPASusannah is being treated in the physiotherapy unit of the Centro das Taipas, a vast, pink former mental institutution close to Lisbon’s airport, where she is having hot towels pressed on to her lower back. Built during the second world war, the wards of wing 21B are these days committed to the treatment of drug addiction.

    Susannah is a long-term drug user and is intelligent but troubled. She first smoked cannabis at 13. At 17, she began taking heroin with the father of her children. Now 37, she has been dependent on drugs – mostly heroin – for almost two decades.

    „I lived in Spain for a while,“ she tells me. „And London for a year, working in the restaurants with a friend. I went there to try to get off drugs but ended up on crack.“ These days, however, Susannah, who also suffers from a bipolar disorder, is one of the beneficiaries of Europe’s most tolerant drug regime. For in Portugal, where Susannah lives, drugs have not only been decriminalised for almost a decade, but users are treated as though they have a health and social problem. Addicts such as Susannah are helped by the law, not penalised and stigmatised by it.

    In the midst of the recently resurgent debate in Britain about whether our drug laws are working – or require a major overhaul – the experience of Portugal has become a crucial piece of evidence in favour of a radical approach that has confounded the expectations of even its conservative critics, so much so that in the last month British officials have asked their Portuguese counterparts for advice, with the only caveat being that they avoid mentioning the word „decriminalise“.

    It is, perhaps, an unnecessary sensitivity. For the reality is that, despite liberalising how it regards drug possession – now largely an administrative problem rather than a criminal offence – Portugal has not become a magnet for drug tourists like Amsterdam, as some had predicted.

    British officials are not the only ones who have made the pilgrimage to Portugal in recent years – health specialists, officials and journalists from around the world have all made the journey to see what Portugal is doing right, even as their own countries are still struggling.

    Nor has it seen its addict population markedly increase. Rather it has stabilised in a nation that, along with the UK and Luxembourg, once had the worst heroin problem in Europe.

    For Susannah – as for the many long-term addicts now on methadone replacement and other programmes, and for the country’s health professionals – the country’s recent social history is divided into what the world of addiction and drug use was like before Law 30 was approved in November 2000, and what it is like now.

    Before the law, which decriminalised (or depenalised) possession of drugs but still prohibited their use, the story of drug addiction in Portugal was a familiar one. More than 50% of those infected with HIV in Portugal were drug addicts, with new diagnoses of HIV among addicts running at about 3,000 a year. These days, addicts account for only 20% of those who are HIV infected, while the number of new HIV diagnoses of addicts has fallen to fewer than 2,000 a year.

    Other measures have been equally encouraging. Deaths of street users from accidental overdoses also appear to have declined, as – anecdotal evidence strongly suggests – has petty crime associated with addicts who were stealing to maintain their habits. Recent surveys in schools also suggest an overall decrease in drug experimentation.

    At the same time, the number of those in treatment for their addiction problems has risen by about a third from 23,500 in 1998 to 35,000 today – helped by a substantial increase in available beds, facilities and medical support – with many going on to methadone replacement programmes. The consequence is that perhaps as much as €400m (£334m) has been taken out of the illegal drugs market.

    But decriminalisation, as Portuguese officials and others who have observed the country’s experience are at pains to point out, was only the most obvious part of what happened 10 years ago in the midst of a similar debate on drugs to the one now going on in the UK.

    Then, in a moment of grand vision powered by an inquiry which recommended a wholesale overhaul of Portugal’s anti-drugs policy in 1998, the government opted to make wholesale changes to the way Portugal dealt with the issue, giving a huge boost in resources to everything from prevention to harm reduction, treatment and reintegration – creating an entirely joined-up approach to drug abuse under the auspices of a single unit in the ministry of health.

    It marked an acceptance that for many, living drug-free was neither realistic nor possible and that what society needed to do was mitigate the risk individuals posed to themselves and a wider population at large by helping them manage their problems.

    Susannah’s doctor, the head of treatment at the Centro das Taipas, is Dr Miguel Vasconcelos. He frames Portuguese drug laws in a way that I hear repeated several times. Within certain clearly defined limits – an amount equivalent to 10 days‘ normal use of any particular drug, ranging from amphetamines and cannabis to heroin – possession, he explains, is now considered similar to a traffic offence. It is a notion I find later described in the Portuguese drug strategy document as a „humanistic“ approach.

    Vasconcelos, 51, is old enough to remember what it was like before, in a country which, two decades ago, barely had a methadone replacement programme at all. In his office, decorated with artworks by his clients, Vasconcelos says: „Critics from the conservative parties were concerned that the new law would make Portugal a place like Amsterdam, but that did not happen.

    „You have to remember,“ he says, „that the substances are still illegal; it is the consequences that are different.“ And for those arrested in possession of drugs for personal use, that means not a court appearance but an invitation to attend a „dissuasion board“ that can request – but not insist upon – attendance at facilities such as the Centro das Taipas for assessment and treatment. „They evaluate if someone is ill or a recreational user, if a person uses sporadically,“ says Vasconselos. „Even then people have a choice. People can refuse to attend the dissuasion board.“

    For many, he believes, the experience can be cathartic and he admits being surprised by how open many of the clients who have come to his facility via that system have been .

    If there has been a problem with the Portuguese experiment, he believes that it has been one largely of perception – outside Portugal – where decriminalisation has been misunderstood by some as legalisation or a step on the road to it.

    Rather, Vasconcelos believes that decriminalisation is a natural consequence of a gradual shift from regarding addicts as social delinquents to regarding them as people in need of help, a view reiterated by Dr Manuel Cardoso, a board member at the Instituto da Droga e da Toxicodependência at Portugal’s health ministry, which now co-ordinates the country’s approach to drug abuse.

    At the centre of Portugal’s deeply pragmatic approach are the dissuasion boards. Lisbon’s board – which deals with 2,000 cases a year – sits in a modest office on the second floor of a block above a pretty park. There are no lawyers (although they can attend) and no clerks in robes. No uniforms at all.

    Last Friday, on one side of the table were Nadia Simoes and Nuno Portugal Capaz, both members of the commission. On the other was a 19-year-old barman in a white T-shirt who allowed the Observer to observe the confidential process but asked not to be named.

    Stopped by police with 5.2 grams of cannabis, he is marginally over the limit of what can be dealt with by the dissuasion board alone and has had to appear in court as well. It is the young man’s first offence. He looks nervous. But it quickly becomes clear that this is a non-confrontational process, as Simoes explains that while possession of drugs for personal use is not a criminal offence, it is still forbidden.

    The man nods his understanding. Simoes explains the risks of smoking cannabis, including schizophrenia, and the sanctions the board can impose for second offences, including a fine or community service. Licences crucial to employment can also be revoked. As the process concludes, the barman looks relieved and promises to stop smoking. As he leaves, Capaz stands up and shakes his hand. The whole thing has lasted less than 10 minutes.

    A sociologist by training, Capaz is a vice-president on the board. He believes that far from Portugal becoming more lenient, the reality is that the state intervenes far more than it did before Law 30 and the other associated legislation was introduced. Before, he explains, police would often not pursue drug users they had arrested, interested only in the dealers. „People outside Portugal believe we had a tougher approach under the old law, but in reality it is far tougher now.“

    Now everyone who is caught with drugs must go before one of the 20 boards in the country to be categorised as either a recreational user, someone with a developing problem, or an addict. And while some 30% choose to refuse to appear at the first summons, most – when threatened with a fine for disobedience – eventually attend.

    Capaz has been involved since the very beginning and is struck by two things. The first is how Portuguese society has come to accept that addicts and drug users should be treated as a social rather than a criminal problem. The second, he explains, is that under the old criminal system all of those caught were supposed to be equal before the law. „With this system,“ he explains, „We do it the other way. We can apply the law in a way that fits the individual.“

    Indeed, the law recognises that for addicts certain sanctions are not appropriate. While recreational users can be fined, the law prevents addicts from having a financial penalty imposed for fear that in trying to raise the fine they might be driven to commit a crime.

    But not everyone is totally convinced. Not even among the people who have dedicated their lives to assisting addicts. Francisco Chaves runs a modern shelter for street addicts close to Casal Vendoso, a place once notorious for its drug problems. „I want to explain first that this is not my profession but a vocation,“ he explains by way of introduction. He wants, however, to pose a „rhetorical question“ which turns out to be more passionate intervention than a debating point.

    He is concerned that under the „humanistic approach“ enshrined in Portugal’s decade-old laws – in its concern for the human rights of the addict – perhaps too much pressure to change may have been taken off addicts. „I worry that it has become too easy being an addict now,“ he says. „They can say: ‚I’ve got clean clothes. I’ve got food. Support. So why should I change?'“

    He says this sadly, because he agrees that addicts should be treated properly but cannot avoid „the paradox of the situation“. „I say it is a rhetorical question because places like this are required. It is a personal, philosophical question.“ But it is one without any obvious answer.

    Outside his office in the large, bright space where addicts are lolling on the sofa, eating or watching television, I encounter Fernando Almeida, 31, who has been a heroin addict since he was 19. A thief – who stole to support his habit – he was recently released from prison and found a place at this centre.

    When he arrived six months ago, he weighed 55 kilos. These days he weighs 73kg and appears both lucid and motivated. „In the old days I used to get hassled by the police. Now the police don’t interfere with me,“ he says. „I used to steal. Now I’m not going to steal anymore. For me the solution is to stop. I’ve discovered food and small things like taking a walk and having a coffee. I’m learning how to work.“

source: http://www.guardian.co.uk/world/2010/sep/05/portugal-drugs-debate

Bridget M. Kuehn

JAMA. 2010;304(3):261-263. doi:10.1001/jama.2010.963

When patients with HIV infection also are addicted to opioids, treating both disorders simultaneously may help improve outcomes and reduce the spread of HIV or other infections transmitted through needle sharing or risky sexual behaviors associated with injection drug use. But accessing such integrated care has sometimes been a challenge for such patients, who generally had to seek care for opioid abuse at addiction treatment centers and primary HIV care elsewhere. This could be logistically difficult and often led to delays in receiving care.

Now, however, buprenorphine prescribing by HIV clinicians is offering patients the option of receiving treatment for both opioid addiction and HIV infection, an approach that a growing body evidence indicates benefits individual patients and public health.

Figure 05072FA
There are currently about 19 000 US physicians certified to prescribe buprenorphine, but experts urge more physicians, particularly those in HIV primary care, to become certified to meet the demand for opioid addiction treatment.

Since 2002, buprenorphine, a partial opioid agonist, has been available in the United States as an office-based treatment for opioid dependence. Physicians who wish to prescribe the drug may under go a training program and become certified through the Substance Abuse and Mental Health Services Administration (SAMHSA) to prescribe buprenorphine (http://buprenorphine.samhsa.gov/). Methadone, a full opioid agonist, remains available through highly regulated, specialized treatment programs.

„Buprenorphine has definitely expanded access [to addiction care],“ said Amina Chaudhry, MD, MPH, an HIV clinician in Baltimore who prescribes buprenorphine. Chaudhry, who is also a medical officer at SAMHSA’s Center for Substance Abuse Treatment in Rockville, Md, explained that even in cities like Baltimore, where there may be specialty addiction programs nearby, the demand for such care often exceeds the available slots. And rural areas may have no specialty addiction programs at all within a reasonable distance.


Studies have suggested that patients with HIV infection and untreated opioid addiction often receive HIV treatment later in the course of their illness, may be less adherent to their antiretroviral therapy regimen, and may engage in behaviors such as unprotected sex or injection drug use that put themselves and others at risk of new infections. But treating patients for both HIV and drug use can improve such outcomes. Although much of this research has focused on the effects of methadone, emerging evidence suggests that buprenorphine has similar benefits and may have a few advantages over methadone treatment for patients with HIV.

A recent randomized trial found that office-based care can improve addiction-related outcomes for patients with HIV and opioid addiction and may lead to faster treatment for addiction (Lucas GM et al. Ann Intern Med. 2010;152[11]:704-711). Gregory M. Lucas, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, and colleagues randomized 93 patients at a Baltimore HIV clinic to receive buprenorphine therapy at the clinic or to receive a referral to specialty addiction treatment elsewhere. Patients randomized to clinic-based opioid agonist treatment with buprenorphine entered addiction treatment much more quickly (84% had initiated such care at 2 weeks compared with 11% in the referral group). During the 12-month trial, participation in opioid addiction treatment was significantly greater in the clinic-based care group (74% participated in such treatment vs only 41% in the referral group). Patients receiving buprenorphine in the clinic also had significantly fewer urine test results that were positive for opioids or cocaine and visited their HIV primary care clinicians more frequently.

However, the researchers did not find differences in HIV-treatment participation or HIV treatment effects between the clinic-based vs referral groups. The authors concluded that the improvements in addiction treatment may have been driven by streamlined access to care because patients referred to outside specialty addiction care may have experienced a delay in treatment initiation. The small sample size may have precluded identifying clinically significant differences in HIV treatment outcomes, they also noted.

The study was part of the Health Resources and Services Administration’s (HRSA’s) Buprenorphine in HIV Primary Care National Evaluation and Support Center (BHIVES; http://www.bhives.org). An analysis of pooled data from 10 sites participating in the HRSA program is under way.

David A. Fiellin, MD, associate professor of medicine at Yale School of Medicine and co-investigator on BHIVES, noted that the program is also probing which approaches to primary care delivery work best in HIV clinics. So far, he and his colleagues have demonstrated in a pilot study that an approach that uses a nurse or other staff member to help coordinate buprenorphine care by overseeing such tasks as urine testing, drug counseling, and medication monitoring can help to reduce drug use among HIV patients, has good retention rates, improves patient function, and promotes patient satisfaction (Sullivan LE et al. Clin Infect Dis. 2006;43[suppl 4]:S184-S190).

Previous studies had suggested that physicians‘ concerns about adherence to antiretroviral treatment by injection drug users with HIV played a role in the likelihood that such patients would be offered highly active antiretroviral therapy or at least experience a delay in receiving such treatment. But results of a French study suggest that integrated treatment of HIV and opioid addiction could allay such concerns. The study found that retention in opioid substitution therapy, either buprenorphine or methadone, is associated with improved virologic outcomes in patients treated with highly active antiretroviral therapy and who had opioid use disorders (Roux P et al. Clin Infect Dis. 2009;49[9]:1433-1440). The study included 53 patients receiving buprenorphine, 28 receiving methadone, and 32 who were not receiving opioid substitution therapy. The median duration of opioid substitution treatment was 25 months.

„Having one-stop shopping for patients means one less barrier to accessing care,“ Chaudhry said.

Buprenorphine also appears to have fewer interactions with antiretroviral drugs than methadone. Elinore F. McCance-Katz, MD, PhD, professor of psychiatry at the University of California, San Francisco, and her colleagues published an article reviewing drug interactions involving methadone and buprenorphine and other medications, including antiretroviral therapies (McCance-Katz EF et al. Am J Addict. 2009;19[1]:4-16). Two HIV medications in particular, efavirenz and nevirapine, have been documented to trigger opiate withdrawal in patients taking methadone but not in patients taking buprenorphine, despite observations of reduced levels of both methadone and buprenorphine when these antiretrovirals were given to patients receiving these opioid therapies, noted McCance-Katz in an interview. A possible reason for the observed differences may be that methadone is metabolized to an inactive substance while buprenorphine is metabolized to norbuprenorphine, which also has opioid effects and may protect patients from experiencing opiate withdrawal, McCance-Katz said.

„It’s very difficult to effectively treat patients [with HIV] if they are in withdrawal,“ she said. „They simply don’t comply with antiretroviral therapy if they are in withdrawal.“

Elevated concentrations of buprenorphine have been documented in patients with opioid dependence and HIV taking atazanavir; such elevated levels were associated with cognitive impairment in a few HIV patients in one case study, while another study in non–HIV-infected patients found only increased drowsiness (Bruce RD and Altice FL. AIDS. 2006;20[5]:783-784 and McCance-Katz EF et al. Drug Alcohol Depend. 2007;91[2-3]:269-278). Such elevations of methadone concentrations have not been documented with atazanavir.

„In general, buprenorphine has fewer interactions with HIV medications, but neither drug has been looked at extensively with many other medications,“ she said, adding that many patients with HIV may be taking a number of medications in addition to antiretroviral drugs.

Integrating buprenorphine treatment into the HIV care setting has another potential advantage: it may be easier for clinicians to spot interactions between addiction and HIV therapies when patients receive buprenorphine treatment at their primary HIV clinic, McCance-Katz said. For example, if a patient receives methadone at one clinic and antiretroviral therapy at another, there may be limited communication between clinicians at the 2 sites and adverse events may not be identified.


About 19 000 US physicians are certified to prescribe buprenorphine and about 640 000 patients are receiving the prescriptions compared with about 4500 certified prescribers and a little more than 100 000 patients in 2005, according to Nicholas Reuter, MPH, senior public health analyst at SAMHSA. But access to buprenorphine therapy in the HIV primary care setting in the United States may be limited. Reuter noted that psychiatrists and physicians specializing in addiction treatment were early adopters of office-based buprenorphine prescribing. Today, 31% of the prescribers are classified as general or family practitioners, 21% as psychiatrists, 15% as internal medicine specialists, and the remaining third are other specialists who are not HIV clinicians, according to Reuter. (SAMHSA doesn’t track the number of HIV/AIDS specialists who are certified to prescribe buprenorphine.)

A survey of about 500 HIV clinicians (49.7% response rate) who attended International AIDS Society conferences in the United States in 2006 found that only 85 (17%) worked in offices that prescribe buprenorphine. Of the 323 physicians who responded, only 67 (21%) were certified to prescribe the drug, and only 19 (6%) had ever done so (Kunins HV et al. Fam Med. 2009;41[10]:722-728). Additionally, when presented with a vignette of an opioid-addicted patient with HIV, only 16% of the respondents endorsed primary care buprenorphine treatment as the best option for the patient compared with 49% who endorsed buprenorphine treatment in a substance abuse treatment program and 31% who endorsed methadone treatment in a specialty program.

Fiellin noted that other BHIVES efforts have found that clinicians may feel they do not have adequate training and resources to provide addiction treatment but are interested in receiving additional training. The clinics that have implemented primary care buprenorphine care as part of BHIVES have received technical support during implementation, and over time their satisfaction with and sophistication at providing buprenorphine care have improved, he noted.

Another program offering resources to buprenorphine-prescribing physicians is SAMHSA’s Physician Clinical Support System (PCSS), which is directed by Fiellin and includes McCance-Katz as among the clinical experts who work with the program. PCSS helps match new buprenorphine prescribers to more experienced mentors who work in similar settings, including HIV primary care. The program also has drafted a guidance document for buprenorphine prescribing to patients with HIV (http://www.pcssbuprenorphine.org/pcss/documents2/PCSS_OpioidTherapiesHIVDrugInteractions_022808.pdf).

SAMHSA is also working with primary care physicians at federally qualified health centers who may be treating many HIV-infected patients. Reuter explained that the agency would like these centers to offer both buprenorphine and methadone, although the latter would require a center to be licensed as an opioid treatment clinic. He noted that SAMHSA’s goal is to make sure there are as many physicians as possible qualified to provide care to opioid-dependent patients, who may require long-term or recurrent care. For example, the average duration of methadone treatment is 6.8 years. „Our concern is that as long as patients remain engaged in treatment they do very well,“ he said. „A number of patients discontinue and the relapse rate is very high.“

Chaudhry emphasized that primary care buprenorphine treatment is not necessarily a replacement for specialty addiction treatment with methadone or buprenorphine. For example, she noted that some patients may prefer to keep their addiction treatment separate from their HIV care.

„The more treatment choices that providers have to offer the better,“ she said.

A Role for Buprenorphine in Prevention?Between 2004 and 2007, of the 152 917 US individuals in 34 states diagnosed with new HIV infections, 13% of them (n = 19 687) were injection drug users, according to the US Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2009;58[46]:1291-1295). For those who are already infected with HIV, buprenorphine treatment may reduce the likelihood they will spread the infection to others through needle sharing or unprotected sexual activity. And for opioid-dependant individuals who are not already HIV-infected, primary care buprenorphine treatment may reduce risky behaviors that put them at risk of HIV infection, according to a recent study.

Lynn E. Sullivan, MD, and colleagues from the Yale University School of Medicine in New Haven, Conn, compared drug-related and sex-related risk behaviors in 166 buprenorphine-treated individuals at baseline, 12 weeks, and 24 weeks (Sullivan LE et al. J Subst Abuse Treat. 2008;35[1]:87-92). Reports of intravenous drug use among the individuals declined over time, from 37% at baseline to 12% at 12 weeks, to 7% at 24 weeks. The researchers also found a decline in reports of sex while the patient or their partner was high between baseline (64%) and 12 weeks (13%), although such reports increased to 15% a 24 weeks, and inconsistent condom use with a regular partner remained unchanged.

Such benefits may be particularly important in regions of the world where HIV transmission is driven primarily by injection drug use. In Eastern Europe and Central Asia, for example, the Joint United Nations Programme on HIV/AIDS estimates that more than 80% of all HIV infections are caused by contaminated injection equipment (http://www.unaids.org/en/PolicyAndPractice/KeyPopulations/InjectDrugUsers/).

The HIV Prevention Trials Network, an international clinical trials network funded by the National Institute of Allergy and Infectious Diseases, currently has a phase 3 randomized trial under way in China and Thailand to assess whether buprenorphine in combination with naloxone (to reduce the abuse potential) decreases drug use and HIV-related risk behaviors (http://www.hptn.org/research_studies/HPTN058.asp). The trial, which is enrolling about 1500 HIV-uninfected injection drug users, will randomize individuals to receive either buprenorphine plus naloxone for 1 year or detoxification with buprenorphine plus naloxone for up to 18 days (with a second detoxification if necessary). Both groups will also receive counseling for HIV risk reduction. The study will assess cumulative HIV incidence and death and frequency of drug use and drug-related and HIV-related risk behaviors in the 2 groups.—B.M.K.

The Vienna Declaration

In response to the health and social harms of illegal drugs, a large international drug prohibition regime has been developed under the umbrella of the United Nations.1 Decades of research provide a comprehensive assessment of the impacts of the global “War on Drugs” and, as thousands of individuals gather in Vienna at the XVIII International AIDS Conference, the international scientific community calls for an acknowledgement of the limits and harms of drug prohibition, and for drug policy reform to remove barriers to effective HIV prevention, treatment and care.

The evidence that law enforcement has failed to prevent the availability of illegal drugs, in communities where there is demand, is now unambiguous.2, 3Over the last several decades, national and international drug surveillance systems have demonstrated a general pattern of falling drug prices and increasing drug purity—despite massive investments in drug law enforcement.3,4

Furthermore, there is no evidence that increasing the ferocity of law enforcement meaningfully reduces the prevalence of drug use.5 The data also clearly demonstrate that the number of countries in which people inject illegal drugs is growing, with women and children becoming increasingly affected.6 Outside of sub-Saharan Africa, injection drug use accounts for approximately one in three new cases of HIV.7, 8 In some areas where HIV is spreading most rapidly, such as Eastern Europe and Central Asia, HIV prevalence can be as high as 70% among people who inject drugs, and in some areas more than 80% of all HIV cases are among this group.8

In the context of overwhelming evidence that drug law enforcement has failed to achieve its stated objectives, it is important that its harmful consequences be acknowledged and addressed. These consequences include but are not limited to:

  • HIV epidemics fuelled by the criminalisation of people who use illicit drugs and by prohibitions on the provision of sterile needles and opioid substitution treatment.9, 10
  • HIV outbreaks among incarcerated and institutionalised drug users as a result of punitive laws and policies and a lack of HIV prevention services in these settings.11-13
  • The undermining of public health systems when law enforcement drives drug users away from prevention and care services and into environments where the risk of infectious disease transmission (e.g., HIV, hepatitis C & B, and tuberculosis) and other harms is increased.14-16
  • A crisis in criminal justice systems as a result of record incarceration rates in a number of nations.17, 18 This has negatively affected the social functioning of entire communities. While racial disparities in incarceration rates for drug offences are evident in countries all over the world, the impact has been particularly severe in the US, where approximately one in nine African-American males in the age group 20 to 34 is incarcerated on any given day, primarily as a result of drug law enforcement.19
  • Stigma towards people who use illicit drugs, which reinforces the political popularity of criminalising drug users and undermines HIV prevention and other health promotion efforts.20, 21
  • Severe human rights violations, including torture, forced labour, inhuman and degrading treatment, and execution of drug offenders in a number of countries.22, 23
  • A massive illicit market worth an estimated annual value of US$320 billion.4 These profits remain entirely outside the control of government. They fuel crime, violence and corruption in countless urban communities and have destabilised entire countries, such as Colombia, Mexico and Afghanistan.4
  • Billions of tax dollars wasted on a “War on Drugs” approach to drug control that does not achieve its stated objectives and, instead, directly or indirectly contributes to the above harms.24

Unfortunately, evidence of the failure of drug prohibition to achieve its stated goals, as well as the severe negative consequences of these policies, is often denied by those with vested interests in maintaining the status quo.25This has created confusion among the public and has cost countless lives. Governments and international organisations have ethical and legal obligations to respond to this crisis and must seek to enact alternative evidence-based strategies that can effectively reduce the harms of drugs without creating harms of their own. We, the undersigned, call on governments and international organisations, including the United Nations, to:

  • Undertake a transparent review of the effectiveness of current drug policies.
  • Implement and evaluate a science-based public health approach to address the individual and community harms stemming from illicit drug use.
  • Decriminalise drug users, scale up evidence-based drug dependence treatment options and abolish ineffective compulsory drug treatment centres that violate the Universal Declaration of Human Rights.26
  • Unequivocally endorse and scale up funding for the implementation of the comprehensive package of HIV interventions spelled out in the WHO, UNODC and UNAIDS Target Setting Guide.27
  • Meaningfully involve members of the affected community in developing, monitoring and implementing services and policies that affect their lives.

We further call upon the UN Secretary-General, Ban Ki-moon, to urgently implement measures to ensure that the United Nations system—including the International Narcotics Control Board—speaks with one voice to support the decriminalisation of drug users and the implementation of evidence-based approaches to drug control.28

Basing drug policies on scientific evidence will not eliminate drug use or the problems stemming from drug injecting. However, reorienting drug policies towards evidence-based approaches that respect, protect and fulfil human rights has the potential to reduce harms deriving from current policies and would allow for the redirection of the vast financial resources towards where they are needed most: implementing and evaluating evidence-based prevention, regulatory, treatment and harm reduction interventions.

source and please sign there:http://www.viennadeclaration.com/the-declaration.html

Drug War Statement Upstaged at AIDS Gathering

VIENNA — Some of the world’s top AIDS experts issued a radical manifesto this week at the 18th International AIDS Conference: They declared the war on drugs a 50-year-old failure and called for it to be abandoned.
No one heard.

Officially, the theme of the AIDS meeting, the world’s largest public health gathering, is the need to attack the rapidly growing epidemic among addicts in Eastern Europe, Russia and Asia. It was held in Vienna because this city is the doorway to the East and, in this German-speaking country, all the conference signs are in English and Russian.

(In a lovely ironic touch, the conference hall is only a few steps from the Ferris wheel in the Orson Welles film noir classic set in postwar Vienna, “The Third Man.” On it, a cynical dealer of counterfeit drugs tells his pursuer to look down at the people below and says: “Victims? Don’t be melodramatic…. Would you really feel any pity if one of those dots stopped moving forever?”)

But the organizers’ efforts to get publicity for the Vienna Declaration, which calls for drug users to be spared arrest and offered clean needles, methadone and treatment if they have AIDS, have come to naught. Almost no one here talks about the war on drugs.

Instead, everyone is publicly worrying that the war on AIDS is falling apart. Donor money is evaporating in the recession, and it is looking likely that only about a third of the 33 million infected people in the world will have any hope of treatment.

Frustration is high. Speakers like Bill Gates were interrupted by demonstrators in Sherwood Forest green calling for a “Robin Hood tax” — a tiny fee on the $4 trillion in currency transactions made daily by banks and hedge funds that could raise billions for AIDS.
Many activists blame the Obama administration, which is shifting its priorities to mother-and-child health. The halls are decorated with posters comparing Mr. Obama unfavorably with George W. Bush. On Wednesday, Archbishop Desmond Tutu criticized Mr. Obama in an Op-Ed article in The New York Times.

In his speech here, former President Bill Clinton said Ambassador Eric Goosby, the administration’s global AIDS coordinator, “ought to get some kind of Purple Heart for showing up.”
However, a new report from the Kaiser Family Foundation shows that the United States still gives more for AIDS assistance than all other countries put together, accounting for 58 percent of contributions. Its donations are still going up slightly, while those from Europe, Canada, Japan and Australia are flat or falling.

Officials from the Global Fund to Fight AIDS, Tuberculosis and Malaria say they fear they will not come close to the $17 billion target they set for their next donors’ meeting in September.
The other, more welcome, distraction has been the exciting results of a South African clinical trial in which a vaginal gel with an antiretroviral drug protected 40 percent of the women using it. This is the first good news about microbicides in decades of work. A gel women can use secretly has long been sought, since many men disdain condoms and many women want to get pregnant.

The Vienna Declaration is only the second time that the International AIDS Society has issued such a document. The last was the 2000 Durban Declaration, which reaffirmed that H.I.V. was the cause of AIDS. It was a response to the government of South Africa, the conference’s host, which at the time denied that the virus caused disease and refused to buy medicine for its citizens.

Outside of Africa, almost a third of all H.I.V. infections stem from drug injections.
The declaration contends that arresting drug users forces them into hiding, spreading the epidemic. It backs “science-based public health approaches“ proved in clinical trials, which can include everything clean needle swaps, 12-step recovery programs and methadone.

Dr. Evan Wood, an AIDS policy expert at the University of British Columbia and the chief author, cited Portugal’s approach. According to a 2009 report by the libertarian Cato Institute, in the decade since Portugal legalized possession of up to 10 days’ worth of any drug, including cocaine and heroin, its AIDS rate dropped by half, overdose deaths fell, many citizens sought treatment, drug use among young people fell and drug tourism did not develop. The institute called the policy “a resounding success.”
The declaration is largely aimed at countries of the former Soviet Union. In Russia, for example, close to 1 percent of its adult population is infected.

Nonetheless, the country forbids all methadone-type treatments, and the national health plan offers only abrupt detoxification, which has a high failure rate. The most frequent victims — prisoners and people not living in their assigned residence areas — are the least likely to get AIDS drugs, and activists say markups vastly inflate the prices of medications bought cheaply by foreign donors.

“The government says everything is fine,” said Aleksandra Volgina, 31, the leader of Candle, a Russian AIDS organization based in St. Petersburg. “We’re even donors to the Global Fund, but we don’t have treatment; we don’t even have prevention.”
She has stayed off heroin thanks to a 12-step program her family paid for, she said, but every month she worries about whether the government pharmacy will have all three drugs she needs, and some of her friends have died for lack of them.
“What’s going on in Russia is being silenced,” she said. “You can’t even knock on the Health Ministry’s door.”

Despite the quasi-Russian cast to the conference, no one from the Russian government attended, sponsors said.
Only two governments reacted to the declaration: Canada, which rejected it, and Georgia, whose first lady signed it in a public ceremony. The tiny former Soviet republic has a history of brutal treatment of drug addicts, Dr. Wood said. But it also has taken to defying Russia, with which it fought a brief war in 2008.

In the large American delegation here, almost every top official refused to discuss the declaration. Finally, one government official, speaking on the condition of anonymity, said he had just called the White House for guidance and was told no one had read it yet and there was no time to respond.

He did note that Dr. Goosby recently announced that countries getting American help to fight AIDS can use it to buy clean needles for addicts, a change from Bush administration policy.
The one exception to the official American silence was Dr. Nora D. Volkow, the normally low-profile director of the National Institute on Drug Abuse, who said she personally agreed with the declaration’s premise.
“Addiction is a brain disease,” she said. “I’m a scientist. The evidence unequivocally shows that criminalizing the drug abuser does not solve the problem. I’m very much against legalization of drugs or drug dealing. But I would not arrest a person addicted to drugs. I’d send them to treatment, not prison.”

Asked if she feared being attacked by Congressional conservatives, she said: “I took this job because I want drug users to be recognized as people with a disease. If I don’t speak about it, why even bother to gather the data?”

Objectives To examine survival and long term cessation of
injecting in a cohort of drug users and to assess the
influence of opiate substitution treatment on these
Design Prospective open cohort study.
Setting A single primary care facility in Edinburgh.
Participants 794 patients with a history of injecting drug
use presenting between 1980 and 2007; 655 (82%) were
followed up by interview or linkage to primary care records
and mortality register, or both, and contributed 10 390
person years at risk; 557 (85%) had received opiate
substitution treatment.
Main outcome measures Duration of injecting: years from
first injection to long term cessation, defined as last
injection before period of five years of non-injecting;
mortality before cessation; overall survival.
Results In the entire cohort 277 participants achieved
long term cessation of injecting, and 228 died. Half of the
survivors had poor health related quality of life. Median
duration from first injection to death was 24 years for
participants with HIV and 41 years for those without HIV.
For each additional year of opiate substitution treatment
the hazard of death before long term cessation fell 13%
(95% confidence interval 17% to 9%) after adjustment for
HIV, sex, calendar period, age at first injection, and
history of prison and overdose. Conversely exposure to
opiate substitution treatment was inversely related to the
chances of achieving long term cessation.
Conclusions Opiate substitution treatment in injecting
drug users in primary care reduces this risk of mortality,
with survival benefits increasing with cumulative
exposure to treatment. Treatment does not reduce the
overall duration of injecting.
Injection drug use is an important public health problem
with a prevalence of around 1-2% among young
adults in the United Kingdom and a standardised mortality
ratio over 10 times that of the general
population.1 Deaths in those who inject opiates are
mainly a consequence of overdose and bloodborne
infection.2 The principal treatment for dependent
users is opiate substitution therapy, commonly oral
methadone,3 which in the UK is mostly delivered in
primary care settings. Opiate substitution treatment
can reduce opiate use, mortality, and transmission of
bloodborne infections, though most evidence comes
from relatively short term studies.4-8
Short periods of cessation from injecting are relatively
common,9 but few studies have long enough follow-
up to observe long term cessation, and the impact
of opiate substitution treatment on the overall duration
of injecting is unclear.10
We report on a follow-up study of the Edinburgh
addiction cohort.11 This study included injecting drug
users, most of whom were using heroin, recruited
through Muirhouse Medical Group, a single primary
care facility in a deprived area of Edinburgh, during a
rapid local HIV epidemic.12 We describe the duration
of injecting and survival and assess the influence of
opiate substitution treatment and other factors on
these outcomes.
Data source
Methods are described in detail elsewhere.11 13 Briefly,
between 1980 and 2006 all patients at a large primary
care facility in Edinburgh who reported a history of
injecting drug use were recruited to the study. Opiate
substitution treatment was publicly funded and accessible
to patients throughout the study period, in keeping
with national guidelines. Cohort members were
flagged with the General Register Office for Scotland
to allow for tracing of deaths and changes of general
practitioner. From October 2005 to November 2007
we attempted to contact all surviving cohort members
to conduct a follow-up interview. Information was also
collected from primary care notes when these were

Read the whole study, it is the longest ever:Methadon, scotland

Researchers at the University of Pennsylvania have demonstrated that morphine withdrawal complicates hepatitis C by suppressing IFN-alpha-mediated immunity and enhancing virus replication. The paper by Wang et al., �Morphine withdrawal enhances hepatitis C virus (HCV) replicon expression,� appears in the November issue of The American Journal of Pathology and is accompanied by a commentary.

Hepatitis C virus (HCV) is common among intravenous drug users, with 70 to 80% of abusers infected in the United States. This high association has peaked interest in determining the effects of drug abuse, specifically opiates, on progression of the disease. The discovery of such an association would impact treatment of both HCV infection and drug abuse.

Dr. Wen-Zhe Ho has been interested in such interplay for some time. His laboratory has previously shown using cell culture that morphine enhances virus replication and inhibits IFN-alpha (a natural anti-viral factor produced by immune, as well as host cells, and the only one approved in recombinant form for treating HCV infection). To further these results, his lab has used a cell model system to determine the consequences of morphine withdrawal, which is a common recurring event in opioid users.

Chuan-Qing Wang and colleagues examined the effects of morphine withdrawal (MW) on HCV-infected cultured liver cells by exposing cells to the drug for four days followed by its removal. They also assessed the effects of using naloxone, to block the opioid receptors, in conjunction with drug removal, i.e. precipitated morphine withdrawal (PW). To measure HCV replication, they used a virus-like �replicon� that mimics the events that occur in liver cells and expression of viral RNA and proteins that HCV uses. Although the replicon does not produce the infectious virus, the HCV replicon system represents the best available system for examining the impact of opiates on HCV at the time of their research study.

Similar to their previous results, the authors found that MW and PW increased levels of HCV replicon RNA and protein expression. In addition, both withdrawal scenarios inhibited IFN-alpha expression in liver cells in the presence or absence of HCV replicon. Since IFN-alpha is a critical self-defense mechanism utilized by liver cells to fight off viral infection, including HIV, this study suggests that morphine withdrawal weakens host cell immunity and provides a favorable environment for HCV growth in the liver.

The authors extended their study by examining the mechanism behind these observations. MW and PW inactivated the IFN-alpha promoter (the switch for making IFN-alpha) by directly inhibiting its activator, interferon regulatory factor-7 (IRF-7), and this effect was more pronounced in HCV replicon-containing cells. Finally, the ability of IFN-alpha treatment to block HCV replicon expression (85%) fell following MW (60%) and PW (50%). This finding, in conjunction with the earlier report by the same group, provides an explanation to the question of why so many HCV-infected patients fail to respond to IFN-alpha treatment.

Although the clinical relevance of this study remains to be determined, these data showing that withdrawal promotes HCV expression by suppressing anti-HCV factor (IFN-alpha) production by liver cells suggests that �opioid abuse may contribute to the chronicity of HCV infection and promote HCV disease progression.� The study also underscores the necessity of future clinical and epidemiological studies to define the role of opiate abuse in promoting HCV disease.

These results suggest that opioid abusers experiencing periods of drug abuse, followed by periods of withdrawal (due to lack of supplies) may lead to immunocompromised liver. These findings further support the need for methadone maintenance treatment as an additional benefit for opioid abusers.

Research was supported by National Institute on Drug Abuse, National Institutes of Health.

This work involved collaborators at Joseph Stokes, Jr. Research Institute at The Children’s Hospital of Philadelphia; The Center for Studies of Addiction, University of Pennsylvania School of Medicine; and The Children’s Hospital of Fudan University, Shanghai, China.

Wang C-Q, Li Y, Douglas SD, Wang X, Metzger DS, Zhang T, Ho W-Z: Morphine withdrawal enhances hepatitis C virus (HCV) replicon expression. Am J Pathol 2005, 167:1333-1340

The American Journal of Pathology, the official journal of the American Society for Investigative Pathology (ASIP), seeks to publish high-quality original papers on the cellular and molecular mechanisms of disease. The editors accept manuscripts which report important findings on disease pathogenesis or basic biological mechanisms that relate to disease, without preference for a specific method of analysis. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, biological, animal, chemical and immunological approaches in conjunction with morphology.

ntravenous (IV) drug users who abuse morphine, then withdraw from it later, may be unknowingly complicating the beneficial effects of their hepatitis C treatment or giving their hepatitis infection an unwanted boost. That’s the conclusion of a study by researchers at Children’s Hospital of Philadelphia, the University of Pennsylvania and in China.1 The findings are published in the November issue of the American Journal of Pathology.
Detrimental Effects of Morphine Withdrawal
Quitting morphine in this population of hepatitis C patients may suppress the benefits of interferon-alfa in the body and enhance the replication of the virus, the study investigators led by Wen-Zhe Ho, MD, a research associate professor in the division of Immunologic and Infectious Diseases at Children’s Hospital of Philadelphia, reported.
According to the study investigators, hepatitis C infection is common among IV drug users; up to 90 percent of such users are infected with HCV in the United States, and one-fifth to one-half have chronic infection.2 The high numbers of these patients with the disease has prompted medical researchers to study the effects of drug abuse, especially the use of opiates, on HCV progression.
„In the case of HCV infection, there is little information about whether drug abuse, such as heroin, enhances HCV replication and promotes HCV disease progression,“ wrote Ho and his team. „This lack of knowledge about the impact of opioid abuse on HCV disease is a major barrier to fundamental understanding of HCV-related morbidity and mortality among intravenous drug users and to the development of new therapeutic approaches for HCV infection.“
The scientists theorized that illicit drugs might be able to detrimentally alter the immune response against the viral infection in some way. Other studies, they pointed out, showed that these drugs have the ability to block the production of beneficial interferons in the body that normally fight the virus.

Morphine’s Effect on Hepatitis C Studied Previously
In a previous study, Ho and his colleagues found that morphine boosted the virus‘ growth and interfered with interferon alfa in a collection of liver cells.3 Interferon alfa is the basis for the pegylated interferon that people with hepatitis C take as medication for the disease today in combination with the antiviral oral drug, ribavirin.4 Also produced naturally in the body, interferon is an antiviral factor produced by certain cells.
The follow-up to that laboratory-based study was the latest research aimed at determining how withdrawing from morphine might affect the course of the disease. „Physical dependence on morphine is characterized by the occurrence of an abstinence or withdrawal syndrome on termination of the drug,“ wrote Ho and his fellow investigators. These abstinence syndromes also can occur during the use of an opioid antagonist such as naloxone (Narcan), a drug that reverses the effects of narcotics, the researchers explained. Thus, they also tested the effect of naloxone-induced morphine withdrawal for the study.
Ho and his team exposed a group of liver cells kept in culture to morphine for four days, then removed it. The scientists also used a model that mimicked the events that occur in liver cells when genetic material (HCV RNA) and proteins used by the hepatitis C virus to create infection are present. This allowed the researchers to mimic the replication patterns of the virus without actually using an infectious virus.
Effects of Morphine Withdrawal
Similar to what they found in their previous study,3 Ho and his colleagues learned that removing morphine boosted levels of HCV RNA (the genetic material used by the virus) and hepatitis C viral protein in the cells. This, in essence, indicates that the viral infection is spreading. However, 72 hours after morphine was removed, HCV RNA levels decreased, suggesting there was only a temporary surge.
Withdrawing the morphine also blocked interferon-alfa production in the liver cells compared to cells in which morphine was not withdrawn. Since interferon-alfa is a critical self-defense mechanism used by liver cells to fight off attacks by the hepatitis C virus or HIV, the findings suggest that drug abusers who quit using morphine can weaken their immune system’s ability to defend the body against an HCV infection, and provides a favorable environment for hepatitis C viral growth in the liver.
Underlying Causes Studied
Next, Ho’s group wanted to understand why removing morphine created such a beneficial environment for the hepatitis C virus. They learned that removing morphine from liver cells blocked the production of interferon-alfa by, in turn, suppressing its activator, interferon regulatory factor-7 (IRF-7). The team also found that the ability of interferon-alfa to block HCV replication (or the model of HCV in this case) fell by nearly two-thirds.
The same detrimental effect of morphine removal also occurred in relation to manmade interferon alfa. This manmade, or recombinant, form is similar to the interferon medication used for people with hepatitis C today. When synthetic interferon was added to the cell lines, they demonstrated a strong ability to fight off the hepatitis virus. However, when morphine was withdrawn from the cells, the anti-HCV ability of interferon-alfa „was significantly diminished,“ Ho and his colleagues wrote.
These results were observed when morphine was directly withdrawn or indirectly removed by using naloxone, they reported, and even to a greater extent in the latter case.
„Collectively, these new observations in conjunction with our earlier findings support the notion that opioid abuse is a co-factor that promotes HCV replication,“ wrote Ho and his colleagues.
The researchers point out that the clinical relevance of this study remains to be determined, but the findings suggest that „opioid abuse may contribute to the chronicity of HCV infection and promote HCV disease progression.“
They recommend both clinical and epidemiological studies be launched to better define the rule of drug abuse in the context of HCV infection. In the meantime, they say drug abusers who use such opioids as morphine, followed by periods of withdrawal due to lack of supplies, may be doing much more harm to their livers.
„Our findings provide a plausible interpretation of the high failure rate of interferon-alfa therapy in intravenous drug users,“ the investigators concluded. „The identification of mechanism(s) involved in morphine’s action on the anti-HCV effect of interferon-alfa has the potential to improve interferon-alfa-based treatment for HCV-infected IV drug users.“
Study Reaction
In an accompanying editorial,5 Kevin Moore, PhD, and Geoff Dusheiko, MD, both professors of Hepatology at Royal Free and University College Medical School in London, write that the findings suggest that IV drug abusers or those receiving opioid substitutes like methadone, and who are infected with HCV, may have more difficulty clearing the virus.
„Until recently, there were no data on the effects of opiates on HCV replication or the development of liver injury and fibrosis, one of the earliest features of progression to cirrhosis,“ wrote Moore and Dusheiko.
„The growing implication from these and other studies is that continued opiate abuse leads to enhanced viral replication, liver injury, and … fibrosis. Further studies are required to determine whether these effects occur in humans, as well,“ they wrote.

To their surprise, researchers at Georgetown University Medical Center (GUMC) have discovered that morphine (a derivate of the opium poppy that is similar to heroin) protects rat neurons against HIV toxicity – a finding they say might help in the design of new neuroprotective therapies for patients with the infection.

The discovery, being presented at the annual meeting of the Society of NeuroImmune Pharmacology, also helps explain why a subset of people who are heroin abusers and become infected with HIV through needle sharing don’t develop HIV brain dementia. This brain disorder includes cognitive and motor abnormalities, anxiety and depression.

„We believe that morphine may be neuroprotective in a subset of people infected with HIV,“ says the study’s lead investigator, Italo Mocchetti, PhD, Professor of neuroscience at GUMC. „That is not to say that people should use heroin to protect themselves – that makes no medical sense at all – but our findings gives us ideas about designing drugs that could be of benefit.

„Needless to say we were very surprised at the findings,“ he added. „We started with the opposite hypothesis – that heroin was going to destroy neurons in the brain and lead to HIV dementia.“

The researchers conducted the study because they knew that a number of HIV-positive people are also heroin abusers, and because of that, some are at high risk of developing neurological complications from the infection. Others, however, never develop these cognitive problems, Mocchetti says.

Because little is known about the molecular mechanisms linking opiates and HIV neurotoxicity, Mocchetti and his team conducted experiments in rats. They found that in the brain, morphine inhibited the toxic property of the HIV protein gp120 that mediates the infection of immune cells. With further investigation, they concluded that morphine induces production of the protein CCL5, which they discovered is released by astrocytes, a type of brain cell. CCL5 is known to activate factors that suppress HIV infection of human immune cells. „It is known to be important in blood, but we didn’t know it is secreted in the brain,“ says Mocchetti. „Our hypothesis is that it is in the brain to prevent neurons from dying.“

They say morphine blocked HIV from binding to CCR5 receptors it typically uses to enter and infect cells. The researchers believe CCL5 itself attached to those receptors, preventing the virus from using it. In this way, it prevented HIV-associated dementia. This effect, however, only worked in the M-trophic strain of HIV, the strain that most people are first infected with. It did not work with the second T-trophic strain that often infects patients later.

„Ideally we can use this information to develop a morphine-like compound that does not have the typical dependency and tolerance issues that morphine has,“ says Mocchetti.

April 17, 2010
Red Orbit

Executive Summary_ _______________________________________________________________ 5
Introduction_______________________________________________________________________ 7
Methodology_____________________________________________________________________ 10
Summaries of Published Studies
Evaluating Insite: Why and How
Reasons for evaluating Insite_______________________________________________________________ 13
How Insite is studied_ ____________________________________________________________________14
Early Results
Attendance, drug use patterns and referrals__________________________________________________ 15
Who Uses Insite?
Characteristics of Insite users_ _____________________________________________________________ 17
Frequent Insite users_ ____________________________________________________________________18
Hepatitis C infection among Insite users_____________________________________________________19
HIV prevalence among Insite users__________________________________________________________21
Younger Insite users______________________________________________________________________22
Does Insite Promote Drug Use?
A before and after study_ _________________________________________________________________ 23
Insite and initiation of injection drug use_____________________________________________________25
Insite and Addiction Treatment
Insite users and detox____________________________________________________________________26
Detox before and after Insite_______________________________________________________________ 27
Impact on Crime and Public Disorder
Insite’s impact on drug-related crime________________________________________________________29
Insite’s impact on public order______________________________________________________________30
Insite and Overdose Prevention
Drug overdoses at Insite_ _________________________________________________________________ 31
Are there more overdoses now because of Insite?_____________________________________________ 33
Insite’s impact on overdose risk____________________________________________________________34
Overdose deaths prevented by Insite________________________________________________________ 35
Impact on High-Risk Behaviour
Insite’s effect on syringe sharing____________________________________________________________ 37
Characteristics of Insite users who share syringes _ ____________________________________________38
Reduced syringe sharing and HIV prevention _________________________________________________39
Insite’s effect on condom use_ _____________________________________________________________40
Safer injecting education at Insite__________________________________________________________41
Insite’s effect on safer injecting practices_____________________________________________________43
Women benefitting from safer injecting education at Insite_____________________________________44
Insite users’ perspectives on safer injecting education at Insite___________________________________45

Read more about Canada:insite_report-eng

Key findings   11
Operation of the world drugs market   11
Production   11
Consumption   11
Revenues   12
Drug-related problems   13
Policies   13
Policy assessment   15
Conclusions   16
Main report: Assessing changes in global drug problems, 1998-2007 19
Peter Reuter
1. Introduction and methodology   21
2. Markets and quantities   23
2.1 Operation of the markets   23
2.2 Production   25
2.3 Consumption   28
2.4 Revenues 31
3. Drug-related problems 35
3.1 Introduction 35
3.2 Drug-related deaths   35
3.3 HIV   36
3.4 Crime   36
3.5 Economic cost estimates 3  6
4. Policies   39
4.1 Introduction   39
4.2 Prevention   40
4.3 Treatment   40
4.4 Harm reduction   41
4.5 Enforcement   41
5. Policy assessment   45
5.1 Introduction   45
5.2 Unintended consequences   46
5.3 Drug epidemics   47
5.4 Production and trafficking controls   49
5.5 Domestic enforcement  51
5.6 Methodological issues  51
6. Conclusions  53
References   55

Abstracts 59
Report 1 59
The operation of the global drug market
Peter Reuter
Report 2 61
Estimating the size of the global drug market: A demand-side approach
Beau Kilmer
Rosalie Pacula
Report 3 63
Issues in estimating the economic cost of drug abuse in consuming nations
Rosalie Liccardo Pacula
Stijn Hoorens
Beau Kilmer
Peter Reuter
Jim Burgdorf
Priscilia Hunt
Report 4 65
Drugs problem and drug policy, developments between 1998 – 2007
Franz Trautmann
Peter Reuter
André van Gageldonk
Daan van der Gouwe
Report 5 67
The unintended consequences of drug policies
Peter Reuter
Report 6 69
Methodological challenges in the country studies
André van Gageldonk
Peter Reuter
Franz Trautmann

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The National Institute on Drug Abuse (NIDA) supports most of the world’s research on drug abuse and addiction.
NIDA-funded research enables scientists to apply the most advanced techniques available to the study of every aspect of
drug abuse, including:
• genetic and social determinants of vulnerability and response to drugs;
• short- and long-term effects of drugs on the brain, including addiction;
• other health and social impacts of drug abuse, including infectious diseases and economic costs;
• development and testing of medication and behavioral treatments for abuse and addiction; and
• development and evaluation of effective messages to deter young people, in particular, from abusing drugs.
Included in this document are selections of topic-specific articles reprinted from NIDA’s research newsletter,
NIDA Notes. Six times per year, NIDA Notes reports on important highlights from NIDA-sponsored research,
in a format that specialists and lay readers alike can read and put to use. Selections like the current one are intended to remind regular NIDA Notes readers and inform other readers of important research discoveries during the periods they cover.