The impact of age on tenofovir-related effects on estimated glomerular filtration rate (eGFR) were explored in a retrospective analysis of 1031 HIV-positive subjects receiving tenofovir as part of their antiretroviral regimen.  Serum creatinine values were used to compute eGFR by the MDRD method.

The average eGFR at baseline was 112.7 mL/min and the median age was 43 years.

In a univariate analysis, there was a decrease in eGFR of 0.016 mL/min for each day of tenofovir use, an effect that persisted after controlling for age, baseline MDRD, race and gender. When age was added to a model controlling for days of tenofovir use, eGFR decreased by 0.638 mL/min for each year increase in age.

Individuals >50 years had an average eGFR 16 ml/min lower than individuals <50 years, which reduced to 4 ml/min lower than those <50 years after controlling for baseline eGFR.  When subjects were further stratified by age (<30, 30-45, >45 years), individuals aged 30-45 had an average eGFR 9.54 mL/min less compared to those <30; individuals >45 had an average eGFR 11.9 mL/min less than those <30 years, after controlling for eGFR at baseline.

comment

The authors of this study concluded that tenofovir may require closer monitoring in older individuals.

Ref: Goeddel L et al. Effect of Age on Renal Function with TDF. 11th PK Workshop, 2010. Abstract 38.

A week-long conference is definitely a good thing in the fight against AIDS but it will count for almost nothing if it is not followed up by concrete measures and action. Since the last global AIDS gathering in Barcelona in 2002 6 million people have died and 10 million have been newly infected, so the question now is: “What will the follow up be?”

Months before the conference kicked off activists were saying that Bangkok had the potential to become a a real turning point in focusing the right kind of attention on drug use and HIV/AIDS issues. They were saying that discussion of HIV control in developing countries usually pays insufficient attention to injecting drug use (IDU). Yet half the population of the world lives in developing countries within a few hours flight from Bangkok, in a region where HIV infection is dominated by the sharing of injecting equipment.

UNAIDS estimates that injecting drug use accounts for 10% of annual HIV infections worldwide, as many as one in three new HIV infections outside Africa, and is the driving force behind the world’s fastest growing epidemics. In Russia, as many as 1 million people have been infected with HIV in less than 10 years, with over 80% of infections being among injecting drug users (IDUs). All the countries of Central Asia and many in Southeast Asia and the Southern Cone of Latin America report that IDUs account for a majority of HIV infections or a rapidly growing share of total cases.

A high prevalence of HIV is now found among IDUs in Myanmar, Vietnam, China, Thailand, Malaysia, Indonesia, Nepal and Iran. In several of these countries, authorities are now reporting that over 60% of IDUs who have been tested are HIV positive. China alone is now estimated to have almost 900,000 injecting drug users, and more than 60% of the country’s 1 million estimated infections are among IDUs. There are also large pockets of HIV-positive IDUs in other populous Asian countries, such as India and Pakistan.

Fuelled by economic, social and political constraints, IDU continues to proliferate in this region as it does in many other parts of the world and what is more frightening is that HIV continues to spread among and from IDUs much more rapidly than the adoption and expansion of effective harm reduction interventions.

The major obstacle remains an entrenched commitment to an unbalanced drug policy heavily reliant on supply control, reinforced by a common but unwarranted fear that expansion of drug policies to include pragmatic harm reduction strategies will conflict with efforts to control the supply of and demand for illicit drugs.

Before the conference, activists from around the globe denounced the fact that drug users still represent a minority of those receiving ARV and called on the international community to ensure the inclusion of injecting drug users in the scale-up of antiretroviral therapy. More specifically, they called on the World Health Organisation (WHO) to ensure the inclusion of injecting drug users in its plan to treat 3 million people by 2005.

Following up a specific proposal made by over 200 drug users, people living with HIV/AIDS, and advocates from around the globe, to include methadone and buprenorphine into the List of Essential Drugs, Dr Andrew Ball, Manager of Regional and Country Support of the WHO HIV/AIDS Department, said during the conference: “The WHO fully recognises the overwhelming evidence that methadone and buprenorphine are highly effective treatments for drug dependence and prevention of HIV/AIDS, and has undertaken an extensive review of the effectiveness of methadone in HIV/AIDS prevention and care.” He added: “An independent expert committee is considering including methadone on the WHO Essential Drugs List,” during a press conference organised by the Open Society Institute, the European AIDS Treatment Group, the Russian Community of People Living with HIV/AIDS and the Thai Drug Users Network.

He said, however, it was not up to the agency to make drugs like methadone or buprenorphine widely available to the public. But the WHO supports the drugs being added to the Essential Drugs List, which is supervised by an independent committee.

The same statement was made by Dr Jim Kim, Director of the WHO’s HIV/AIDS programme, at the end of a colourful demonstration comprising people living with HIV, drug users and sex workers, who called for action and accountability to stop the spread of AIDS before the conference opening. Kim emphasised that experience in many countries had shown that criminalisation of drug use only escalated the spread of AIDS.

Fearing the International Aids Conference was just another talk shop with empty promises, more than 1,500 people from all over the world joined the march, clutching banners and wearing various styles of slogan-bearing T-shirts to voice their demand to be included in the action plans. For Thais, the major demands – which were passed to Prime Minister Thaksin Shinawatra – included ensuring sustainable coverage for the cost of anti-retroviral therapy and the immediate end of Thaksin‘s all-out war on drugs, in which more than 2,500 drug users were killed under questionable circumstances.

An estimated 100,000 to 250,000 people in Thailand inject heroin, even though methamphetamine pills have overtaken heroin as the country’s drug of choice. HIV prevalence among the country’s heroin users has stood at 40% or more since the late 1980s, in contrast to the declining rates among others at high risk. Drug users face limited treatment options and regular abuse by police, including beatings, false arrest and forced confessions. The zero-tolerance Thai campaign’s only effect was to drive intravenous drug users, who reportedly make up about 40 per cent of Thailand’s Aids patients, underground.

The Thai government crackdown began in February 2003 for the official reason of curbing the trade in methamphetamine tablets. Within 3 months, an estimated 2,275 drug suspects were shot dead. Scores of alleged drug dealers were placed on poorly prepared government “blacklists” and ordered to report to the police and many were shot by unknown gunmen shortly after leaving the police station. In addition to almost 3,000 unexplained deaths, thousands had been forced into drug treatment in military-style boot camps.

Not surprisingly Prime Minister Thaksin Shinawatra’s controversial war on drugs came back to haunt him during the opening ceremony. When Thaksin insisted in his speech that his government no longer treated drug users as criminals but as patients, demonstrators and hecklers reminded him of the controversial campaign that was condemned by the international community, including the United Nations. “Thaksin Lies” read one sign that went up in the packed auditorium. Activists reacted in uproar when their representative, Paisan Suwannawong, former heroin addict and chairman of the Thai Treatment Action Group, was designated as the last speaker at the opening ceremony of the Conference. By the time he reached the podium, Prime Minister Thaksin and UN Secretary General Kofi Annan, had already left the hall.

In contrast to claims made by conference organisers that people living with HIV/AIDS had been given wider access than ever before, activists said they continued to be ignored and even discriminated against by people in power. “What hypocrisy,” said Paisan, also leader of the Thai Drug Users Network. “Thaksin said in his speech that he cares and wants to help drug users, so why didn’t he stay to listen to me.”

All through the conference, activists called for a worldwide reversal of public opinion on injecting drugs use. They said in many countries drug users have set up their own organisations that work to reduce the spread of infectious diseases, to decrease discrimination against drug users in society, and to improve medical treatment of all sorts for drug users.

At the eve of the conference, the International Harm Reduction Programme (IHRD) of the Open Society Institute released a report detailing successful efforts to offer drug users antiretroviral treatment (ARV) and the dangers of failing to do so. “The common assertion that drug users cannot comply with treatment represents a failure of vision by AIDS programme administrators, not a description of reality,” said IHRD programme officer Konstantin Lezhentsev, noting that the report described successful efforts to offer ARVs to IDUs in Brazil, Argentina, and a number of urban settings in Western Europe and the US. “The question is whether governments and healthcare systems will step up to their responsibility to meet the specific needs of this group, or continue to simply deny treatment to drug-users based on the myths that are based more on prejudice and discrimination than on healthcare and human rights principles.”

Activists underlined the importance of shifting both from the medical model – according to which IDUs are sick, they cannot adhere to treatment, and they have worse clinical outcomes – and the criminal model – by which they need to be charged and incarcerated, since they perpetuate a cycle of criminality that goes beyond just drug use. It is necessary to admit that when given proper access to healthcare, IDUs can adhere to treatment and have comparable clinical outcomes to other patient populations. It is time to accept that criminality is not caused by drug use but by the same criminal system. Eliminating repressive drug laws and stopping widespread propaganda that blames IDUs for social and economic evils of all descriptions, and halting government-sponsored campaigns that murder them, can only support the functioning of IDUs in society.

Most importantly, they committed to establishing better and stronger links with drug users and harm reduction networks, noting that in most cases drug users’ organisations also work for the decriminalisation of drug use. “What once was radical has to become common sense,” said Paul Davis of Health Gap USA.

Harm reduction and HIV treatment activists have been building their capacity for the last year to arrive at this successful point. In spite of enormous challenges, involving legal, cultural, and moral dilemmas, a formidable and growing array of committed individuals and groups has now entered the battle.

They are trying to raise global awareness to the fact that no area more than drug use clearly demonstrates the bad consequences of abstinence based approaches, and that although in 7 out of the 10 UNAIDS regions (accounting for 90% of the global population) injecting drugs is considered among the most important risk factors for HIV, in many countries injecting drug users are still stigmatised, routinely excluded from treatment, and treated badly by various institutions along a continuum that has insults at one end and violent death at the other.

Unsurprisingly, exactly the same countries where discrimination creates the conditions of furtive drug injection using shared injection equipment are those where HIV prevalence among people who inject drugs is higher. This includes the United States. Despite the American impulse to tell other countries how to do it, the timing and scale of implementation of HIV prevention measures for IDUs in the USA has been anything but impressive, with at least 36% of new AIDS cases in the USA still directly or indirectly associated with injecting-drug use.

Although on 20 February, 1933, the US Congress acknowledged the failure of alcohol Prohibition, it seems that US officials have a strong incentive to maintain their faith in old paradigms even as the facts become increasingly difficult to explain within that paradigm, proving that attitudes toward drug users are often based on beliefs, misconception, moral certainty and “common sense”, rather than on medical evidence.

Evidence tells us a very different story: that drug users can do as well as anybody else and that even the poor and the homeless can adhere to ARV. Their exclusion from treatment and care has nothing to do with science. Rather, it has to do with a widespread discrimination toward active drug users.

So the only measure of both our success and our failure will be the number of lives that are saved, the adoption and implementation of evidence based policies to ensure comprehensive harm reduction approaches to prevention, care and treatment, the elimination of criminalisation, stigmatisation, and marginalisation of drug users, and a substantial reduction in the number of drug users sent to prisons.

AIDS reminds us that all transmissible diseases are rooted in social and economic life, and that respect for human rights and human dignity are paramount in responding to the epidemic. We have heard too many sad stories from Africa, where endless discussions were just an attempt to hide the real reason for not making treatment available, to let authorities do the same on injecting drug use.

Support from international organisations for equitable and comprehensive treatment for HIV-positive or at-risk drug users is growing dramatically as we can see from the UK Department for International Development, the Global Fund to Fight AIDS, Tuberculosis, and Malaria, the World Health Organisation, and UNAIDS.

History will tell us whether their commitment to address the social, cultural, legal, and medical barriers that deprive IDUs of access to HIV treatment will result in effective changes in policies and laws. But while there are many declarations of positive intentions and good meetings taking place, it is up to us, the community, to speak out, advocate, and make our voice heard.

Mauro Guarinieri is Chair of European AIDS Treatment Group (EATG):
http://www.eatg.org

More information on acces for IDUs:
http://www.ceehrn.org/ARV4IDUs

Speech to the Opening Ceremony, XV International AIDS Conference, Bangkok.

I would like to tell you a little bit about myself. I grew up in one of Bangkok’s biggest slums, not far from here. I saw many people using drugs, but never imagined that I would become a drug user myself. The first time I smoked marijuana, it felt like a challenge because all the public campaigns said drugs were “bad” and “dangerous.” I found it wasn’t true, so I continued to smoke it. Then I started smoking heroin, and became addicted without realising it. I didn’t have any money, I was feeling withdrawal symptoms, and my friend offered to share his heroin and inject me. Yes, it was scary the first time.

I got arrested at least 20 times. Most of the time, I did not have any drugs on me. The police would plant drugs on me and force me to confess, and beat me if I did not sign their document. I could not carry a needle around, because if the police arrested me, the charge would be more serious. I heard about the risk of getting HIV from sharing needles, but when you are craving heroin, you don’t think about anything else. You just want to inject.

I was in prison twice. The conditions were terrible and we had to stay in our cells for more than 15 hours a day. For me, there is nothing worse than losing your rights and your freedom. I am not surprised that people use drugs and inject in prison, even if they never used or injected before. I believe that I got HIV in prison because I injected almost every day there.

Getting off drugs is not easy. Many times, I went into drug treatment just to please my family, to get away from the police, or to take a break because the amount of drugs I needed was getting expensive, not because I wanted to quit; and the attitudes of treatment staff only made me feel worse. Other times, I really did want to quit, but can you imagine how it feels to leave a treatment programme and go back home, with nothing to do? How difficult it is to find a job and explain where you’ve been? My own family would watch my every move; I could see in their eyes they did not trust me. I was too embarrassed to see my friends, whose lives seemed so successful. It was so lonely. I felt I had nothing at those times. The only thing I could think of was to go back to using drugs.

Finally, I got off drugs 13 years ago. I knew I really needed help. I decided to go to a “TC,” or “therapeutic community.” This is how I found out I had HIV. The test still is a requirement for entering the TC. There was no pre- or post-test counseling. In fact, my results were given to my sister, not me. Today, not much has changed. Drug users are still seen as morally weak and bad people. We face stigma and discrimination in society and in the health care setting. We experience constant police harassment and ineffective services. In Thailand, injecting drug users or “IDUs” are the only group whose 50% HIV prevalence has not changed in 15 years. One third of all new HIV infections are IDU-related, and this number is increasing. Yet there has been no effective response from the government.

In a recent war on drugs in Thailand, over 2,500 people were killed extra-judicially in the first three months of the campaign. More than 50,000 people were arrested, hundreds of thousands were forced into military-run rehabilitation centres, and drug users were forced underground and away from services that were already difficult to access. Last year, the Thai Drug Users’ Network developed a proposal for a peer-driven HIV prevention, care and support intervention for injectors, and submitted it to the Global Fund. We had to bypass the country coordinating mechanism and lobby with the help of international AIDS activists to get political support for our proposal. In October, we were awarded a $1.3m grant, but we still haven’t received the money. Even though the Thai government says its current policy is to treat drug users as “patients,” not “criminals,” it is still illegal to be a drug user. We continue to be arrested and offered the choice of prison or military-run rehabilitation centres. Is this harm reduction or harm production?

Every minute, a person is infected with HIV by using a dirty needle. Globally, 1 in 3 of all new HIV infections outside of Africa is IDU-related. In fact, contaminated needles account for the largest share of new infections in Eastern Europe and Asia. The WHO says drug users have an equal right to all levels of care, but in practice, we are denied access to ARV treatment, as well as basic prevention interventions like clean needles. Methadone is still illegal in many countries and should be on the WHO Essential Drug List. There are many harm reduction interventions, including clean needles and methadone, which have been proven to help IDUs stay free of HIV. We need these means of prevention in place now. And we need access to treatment now. Drug users, like other politically, socially, or economically marginalised groups, are easily abused by the government and others, who exploit them for money or services. We often do not enjoy even the most basic human rights. In Thailand, this is true for sex workers, MSM, migrant workers and undocumented citizens as well.

The world we live in today is not a world of sharing but of advantage-taking, profit-seeking, and competition to “get ahead.” It is a world motivated by greed and controlled by corporations, which do not recognise the value of a human being. While an elite few amass enormous wealth, basic needs are denied to many millions. Today, many of our governments are run by this elite, who are more interested in protecting their personal investments than promoting public welfare. They invest public resources in projects whose profits go into the pockets of their friends instead of providing for the welfare of society. Governments privatise our public utilities, as well as our education and health care systems. Social welfare programmes and other forms of assistance become issues of charity, not rights or entitlement. As a result, our public hospitals are overloaded and under-funded, severely compromising the availability and quality of treatment and care offered. Of course, tackling AIDS isn’t just about health care and ARV.

Prevention, harm reduction, poverty reduction and decent living standards are all part of the process; but governments, like the United States, or international organisations, like the WTO, make the task much more difficult. Market-driven policies and the emphasis on “abstinence-only” have already proved to be harmful or, at best, totally useless. It is outrageous that today, conservative groups, especially in the US, are advancing a moralistic ideology that contradicts scientific evidence about HIV prevention. Though condoms and clean needles are the most effective tool we have to prevent the transmission of HIV, programmes that promote them are not funded, or are de-funded. Evidence shows that widespread access to ARV leads to huge improvements in health and quality of life, with significant reductions in health care and other costs, because of improved health and productivity among people living with HIV/AIDS and their families.

The most painful experience I can think of, after living with HIV for 13 years, is being poor and HIV-positive. Again and again, I watched many friends die in front of me, from terrible opportunistic infections, simply because they were poor and could not afford treatment. What kills us is not AIDS, but greed. Multi-national pharmaceutical companies inflate the prices of their drugs without thought for poor people. They use they wealth to influence US and European government policy to ensure that intellectual property rights are weighed in their favour. Other governments say they are too worried about adherence and drug resistance to offer treatment, when the truth is they don’t want to pay or suffer repercussions from their trading partners by breaking patents. Four years ago, Thai people with HIV/AIDS asked the government to use a compulsory licence for ddI, but the government was too afraid of trade and other sanctions from the US. Ultimately, we took Bristol Myers-Squibb to court and won the right to produce tablet-form ddI, locally. In the final judgment, the Thai court ruled that, because patents can lead to high prices and limit access to medicines, patients have the right to sue the patent holder. This was a very important battle that we won. But the war is not over.

Recently, the Thai government entered Free Trade Agreement negotiations with the United States. We know the US unilaterally pushes for intellectual property protection that is stricter than what is agreed internationally. This means that Thailand, now producing generic ARV for most who need it, will no longer be able to sustain this important programme. We are demanding the Thai government refuse to trade away the health of its people by negotiating intellectual property protections for medicines.

The US government and its policies affect the ability of people all over the world to enjoy their basic rights and needs. Many poor countries cannot provide basic services like health care because they have to pay back enormous debt to the US and Western Banks. While thousands die of AIDS everyday from lack of funds, there is unlimited funding for war. Billions of dollars are freely available for the killing and destruction in Iraq, while the Global Fund is out of money. This is because of the broken promises of rich donor countries that refuse to pay their fair share. I have no simple solutions for achieving world peace, but I do know that the US government, led by that criminal, George Bush, wages war and occupies countries like Iraq in the name of peace. The US is too arrogant to listen to the UN, and the Thai government shows its loyalty to the US by sending Thai troops to Iraq.

Four years ago, at UNGASS, after activists demanded an urgent response to the global AIDS treatment crisis, Kofi Annan called on all the world’s governments to develop what he described as a “war chest.” This became the Global Fund. At the last International AIDS Conference, WHO launched its ‘3 by 5’ initiative; yet, today, 6 million people are still waiting for their drugs. AIDS doesn’t wait and neither do we. Faced with the abuse of power and greed of corporations, we cannot wait for our governments to act.

Governments and corporations hate activists because we know what they are up to, and we are pulling the masks of fake concern from their face to reveal their true nature. But to me, activists are to be honoured. Activists are my true friends. They stand by my side when I face discrimination and injustice. They have the courage to stand up to those in power who use their positions for their own benefit. They are the ones who can help provide a way forward to fight AIDS and injustice in this world. Access for all is the theme of this conference and the dream of many of us here. Yes, it’s not easy to achieve in the world we live in today, but the world belongs to all of us to change.

Five years ago, doctors, nurses and many other people told me and my friends that ARV was an impossible dream. Recently, Thailand announced that it would provide ARV to all who need it, starting with 50,000 people by the end of this year. Today, I urge all of us to dream: of a day when our world will be filled with love, sharing and peace. And I believe that when we dream together, our dreams come true.

The webcast of this speech (which was also given at the closing ceremony) is available online:
http://www.kaisernetwork.org/health_cast/hcast_index.cfm?display=detail&hc=1185

Human Right Watch on Thailand:
http://www.hrw.org/campaigns/aids/2004/thai.htm

Thailand: Not enough graves: the war on drugs, HIV/AIDS, and violations of human rights. Human Rights Watch Report. Vol 16 No 8, June 2004:
http://www.hrw.org/reports/2004/thailand0704/thailand0704.pdf

CNN report on brutality of Thailands anti-drug policy:
http://www.cnn.com/2003/WORLD/asiapcf/southeast/05/07/thailand.drugs

Links to reports, pictures and transcript of activist groups at the conference:
http://www.actupny.org/reports/Bangkok/