TREAT Asia Site Profile: Children at the Crossroads
HIV-NAT conducts critical clinical trials of pediatric HIV treatment
July 2004—About 70 children in Thailand are participating in a much-neglected arena of the fight against AIDS. They are taking part in clinical trials investigating the effects of antiretroviral therapy on young people that are being conducted by the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT).
In many countries, children are born HIV positive; and in many countries, antiretroviral (ARV) therapy is widely available. But these two circumstances often do not intersect. In Thailand the increasing availability of ARV drugs, combined with a population of children who are HIV positive, is giving clinicians an important glimpse into how children tolerate HIV medicines and fight HIV infection.
“In most countries, like the United States and Australia, most children are not born infected any more because of mother-to-child-transmission (MTCT) interventions,” said Dr. Chris Duncombe, Senior Trials Physician at HIV-NAT. “And in areas like Africa, resources are primarily focused on prevention, treatment of adults, and MTCT. Treatment in children is actually quite limited and so there are many unanswered questions.”
It is important to understand how children tolerate and respond to ARV treatment, Dr. Duncombe said, because “children are not just small adults. They have much higher viral loads and their CD4 counts are quite different. The regimens and dosing we recommend for adults don’t necessarily help children.”
Which is why HIV-NAT is conducting clinical trials to determine when to start treatment in children and what effect ARV therapy has on cognitive and behavioral development, and to understand the patterns of drug resistance experienced by children who have been exposed to several drugs. The results will help establish guidelines for treating HIV-positive children in resource-limited settings—information that will be invaluable as growing numbers of children in the developing world gain access to treatment.
Founded in 1996, HIV-NAT, one of the Thai sites in the TREAT Asia network, is overseen by directors Dr. Praphan Phanuphak, Director of the Thai Red Cross AIDS Research Centre, Dr. David Cooper, Director of the National Centre in HIV Epidemiology and Clinical Research at the University of New South Wales, Australia, and Dr. Joep Lange, Chief Scientific Adviser at the International Antiviral Therapy Evaluation Centre in the Netherlands.
The mission of the collaboration is to conduct HIV clinical trials according to international standards, to develop ARV therapy that is appropriate to developing countries and resource-constrained settings, and to educate and train the health care workforce.
“HIV-NAT has served as a treatment center for eight years. More than 1,800 patients have received treatment,” said Dr. Praphan. “It also serves as a center of excellence where new treatments are tried first and a training center for HIV medicine where physicians learn how to treat patients. Finally, HIV-NAT plays an advocacy role by demonstrating that treatment works.”
Tailoring Treatment to Asia
There are approximately 670,000 people living with HIV in Thailand. Using money from the Global Fund to Fight AIDS, Tuberculosis and Malaria, the country’s goal is to have 50,000 on treatment in the public sector by the end of 2004.
HIV treatment can be expensive and can create side effects sometimes as debilitating as the virus itself. So creating treatment strategies that reduce cost and minimize side effects is an important goal. To that end, HIV-NAT is investigating structured therapy interruption. One of the collaboration’s adult trials, STACCATO, is looking at therapy guided by CD4 counts in comparison to continuous ARV treatment. The study has already shown that “week on, week off” therapy is ineffective. Another large study is comparing the use of interleukin-2 in combination with ARVs, and ARVs alone. These two studies have enrolled more than 600 patients altogether in Thailand.
Dosage is another crucial question in countries like Thailand, where patients receiving treatment often weigh much less than the patients on whom the drugs were initially tested. Using HIV-NAT’s recently established pharmacokinetic laboratory, investigators are researching the appropriate doses of drugs such as indinavir and efavirenz. HIV-NAT has discovered that doses of these drugs that are commonly recommended in Western countries are probably not suitable for some Asian patients.
Three-quarters of the patients who come to HIV-NAT and its affiliated sites in Bangkok are residents of the city. The remaining 25 percent come from outlying provinces. “People travel to HIV-NAT because they get free therapy, good care, and viral load and CD4 counts,” said Dr. Duncombe. Though drugs in Thailand are relatively inexpensive (approximately one US dollar a day, in most cases), one viral load test costs the same as a month of medication. So the additional services that HIV-NAT provides are a boon to Thais living with HIV.
At each visit, patients are seen by a physician, a clinical trials nurse, and, if necessary, a counselor. Most counseling is directed at treatment adherence. “The two biggest issues we face,” said Dr. Duncombe, “are treatment failure and side effects.” Many of the patients experience problems with protease inhibitors, including body composition changes and diabetes.
As Thailand and the world strive to reach ambitious treatment goals, such as the World Health Organization’s “3 by 5” plan (to have three million people on antiretroviral therapy by the end of 2005), proper training of the health care workforce is imperative. Doctors, nurses, and other staff will need to administer complicated regimens of drugs and contend with side effects, treatment adherence issues, and treatment failure.
To prepare the workforce both in Thailand and Asia, HIV-NAT organizes an annual symposium on HIV medicine, with TREAT Asia and the US National Institutes of Health (NIH) as major sponsors. The symposium, held for the seventh time this January, brings together more than 400 physicians and health professionals from the region to talk about the latest research and treatment information.
Throughout the year, HIV-NAT also sponsors doctors from countries around the region to train in Thailand and has developed training courses that have been used in Viet Nam, Myanmar, and China.
Looking Toward a Cure
HIV-NAT’s newest venture is the Australia, Thailand Vaccine Consortium, established in March 2003. With funding from NIH, the researchers are developing a DNA prime, recombinant fowlpox boost HIV vaccine. The hope is that injections of DNA and fowlpox, a virus found in birds, encoded with HIV genes will induce the immune system to respond to HIV. Two vaccines have been produced, a B subtype vaccine for trial in Australia and an A/E subtype vaccine which will be tested in Thailand. Studies to ensure the safety of the Australian vaccine have been completed in healthy human volunteers in Sydney. The Thai trial will begin in late 2004.
“HIV-NAT demonstrates to the world that good therapeutic research can be carried out in developing countries, both from a scientific and ethical standpoint,” said Dr. Praphan. “We also believe that it serves as an inspiration for other countries to follow.”