An Interview with Dr. Jintanat Ananworanich—Taking Care of the Children
February 2006—The number of HIV-infected children in Asia has dropped over the last few years, but treatment for more than 120,000 HIV-positive Asian children remains a daunting challenge. Scarce and prohibitively expensive pediatric drug formulations and inadequate pediatric treatment education are just two factors that have led to a situation in which only a small fraction of children who need antiretroviral drugs (ARVs) are receiving them.
Dr. Jintanat Ananworanich has been a clinical trials physician and pediatrician at the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) since 2000. She speaks and lectures internationally about HIV/AIDS, and her research has been published in leading medical journals such as The Journal of Acquired Immune Deficiency Syndrome, The Lancet, and Pediatric Infectious Diseases.
TREAT Asia Report: How did you become involved in pediatric AIDS?
Dr. Jintanat Ananworanich: I first became interested in HIV when I was studying immunology in preparation for going to the United States to do my residency. I was fortunate enough first to spend a year working as a volunteer researcher in the lab of Dr. Tony Fauci, director of the National Institute of Allergy and Infectious Diseases, under the direction of Dr. Drew Weissman. They were working on dendritic cell research in HIV. Afterwards, when I went to the University of Chicago for my residency, I had the chance to take care of children with HIV infection and that also appealed to me.
Dr. Jintanat Ananworanich
So it’s both the clinical and the basic science of HIV that attracted me. When it came time to select a fellowship, I chose an immunology program involved with the care of children with HIV. And when I came back to Thailand, I specifically looked for an organization that was involved with both children and adults with HIV. At first there were no children at HIV-NAT, so I started working on adults and then gradually tried to start pediatric HIV research here.
I’m drawn to children with HIV, I think, because they are really so young. I feel a lot for them. They are born with this deeply misunderstood infection, and they have to go through tremendous difficulties. It’s not just a physical disease, it’s also a social disease. Taking care of the child as a whole—not only medically, but also helping with how they cope and how they grow up—that, I think, is a very fulfilling field of medicine.
TA Report: How many children would you say are HIV positive in Thailand now?
Dr. Ananworanich: The Thai government reports about 32,000 children have been infected with HIV, of whom 20,000 are still living, so about 12,000 have died. But the numbers are probably underreported. Experts in Thailand feel that the total number of children with HIV is probably closer to 50,000.
Fortunately we have very few new cases now because programs have been instituted to prevent mother-to-child transmission. Right now we probably have up to 600 new cases per year among children. Ten years ago that number would have been closer to 1,000.
TA Report: TREAT Asia is now in the process of setting up a network and a database to track the treatment of HIV among children in Asia. What contributions do you think a TREAT Asia pediatrics network could make?
Dr. Ananworanich: I think that if TREAT Asia can do for pediatrics what the network’s adult program has been able to do, that would be great. A lot of information we have on pediatrics comes from Western countries and it may not apply to children in Asia. Treating children here in Thailand is very different compared with treating them in the U.S., and the appropriate regimens and doses may not be the same.
In Thailand we’ve gone through tremendous changes since the beginning of the epidemic when there was hardly any access to HIV medication. Now we do have access, but the drugs that we have are not all ideal for children. So we end up using a lot of adult formulations. Sometimes there are supply interruptions in the stock provided by the Thai government and we have to use creative measures to make adult formulations usable for children.
Right now pediatricians are treating kids by using what works for adults. To have more data through the TREAT Asia group and be able to share experiences among doctors in Southeast Asia would be very helpful.
TA Report: Is drug resistance among children with HIV a significant problem?
Dr. Ananworanich: To follow children with HIV, we employ clinical exams and CD4 tests—white blood counts. Of course, CD4 is the best measure we have for clinical outcomes. But even when children are under treatment, we really don’t know whether they are developing drug resistance unless we know what their viral loads are.
Most of the time when we see children whose treatment is failing them, it’s already too late—by that point they have low CD4 counts so we must move on to the next salvage regimen. Second-line therapy or salvage therapy is a big problem now in Thailand, and I think it will be in other countries in this region unless access to antiretroviral drugs improves. Because treatments based on non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the main first-line regimen, we usually see children with resistance in the classes of nucleoside reverse transcriptase inhibitors (NRTIs) and NNRTIs, so we’re really left with just protease inhibitors (PIs). But the ideal dose for children on many PIs is really not known and the formulation is not ideal for them.
One PI, Kaletra, comes in a liquid formulation and it has the best data for treatment outcome but it is very expensive. We also don’t have access to Kaletra, so I think this will be the main problem for us in the future.
TA Report: Are any generic medications being created specifically for children?
Dr. Ananworanich: We have many generic drugs in Thailand, but in order to treat the broadest range of patients the generic drug manufacturers are concentrating on making the NRTI and NNRTI classes. And in those classes we don’t have liquid formulations for all of the drugs—liquid being the easiest to give children and the most precise for dosing. So we have to use open capsules or crushed pills.
For protease inhibitors now we only have nelfinavir, which is generic. The Thai Government Pharmaceutical Organization is trying to make other protease inhibitors but they’re harder to manufacture than NRTIs and NNRTIs. If we compare Thailand with other countries in Africa, they get a much lower price for protease inhibitors and for other drugs. Thailand is not resource poor enough to qualify for them, but we’re also not rich, so we’re in a dilemma because we can afford the basic drugs but we can’t afford beyond that.
TA Report: HIV-NAT was created almost a decade ago in part to demonstrate that high-level clinical research could be conducted in Thailand, and by extension in other less developed parts of the world where HIV/AIDS has become a problem. How successful do you think this experiment has been?
Dr. Ananworanich: I think it’s been very successful. HIV-NAT came about because of the interest of the three co-directors—Dr. Praphan Phanuphak of the Thai Red Cross, Dr. Joep Lange of the Netherlands, and Dr. David Cooper from Australia. Since its start in 1996, HIV-NAT has grown tremendously from two employees to 80. Currently we have 27 ongoing studies and we’ve completed more than 50 others.
The research that HIV-NAT has performed has had an impact on Thailand’s national treatment guidelines. We have shown that certain drugs can be used in lower doses in Thai patients than in Western patients. In some instances we can use once-daily dosing instead of twice-daily. We have also performed advanced research using drugs that are just coming out in the West and are not available in Asia. For instance, right now we’re conducting research on drugs to treat people who have developed resistance to other medication. Normally the patients would not have access to these treatments. Now, because of our high-level clinical trials and the outcomes data we’ve generated, drug companies are more interested in bringing new and experimental ARVs to HIV-NAT.
HIV-NAT’s success, I think, is also a good example for other organizations because we’ve shown that effective, high-quality research can be performed in Asia. But it wasn’t easy getting started. When you have never done research, it’s very hard to get funded. The connection between the Thai Red Cross and the two international collaborators really helped because Drs. Cooper and Lange, with their connections, were able to convince funders to support HIV-NAT. Once we had done a few studies and demonstrated that we could do a really good job, then we got more funding.
When I first joined HIV-NAT, it was really hard to get funding for pediatric studies because we didn’t have a track record. Now, we have U.S. National Institutes of Health funding and we have drug company funding to do studies on children.
TA Report: The number of infections in Thailand is climbing in certain vulnerable populations, particularly among young people, men who have sex with men, drug users, and migrant groups. How significant a problem do you think this could be for Thailand?
Dr. Ananworanich: It’s a growing problem of great significance. It’s not just intravenous drug users and migrants, but now it’s also friends who have slept with friends without protection. With young people, the thinking is that friends are trustworthy and therefore you don’t need protection.
Having premarital sex in Thailand is still frowned upon—it happens but it’s not supposed to—so it’s hard to speak honestly to students and young people who are having unprotected sex. People aren’t being open about it and it’s difficult for them to be comfortable using condoms and going to centers to get protection. I don’t think the country has a clear strategy for how to deal with it.
Public education and prevention efforts here could be better. You know, we’ve gone through a lot in Thailand, and over the last ten years we’ve done so well fighting HIV and AIDS. But the population I deal with doesn’t have a good knowledge of HIV. A lot of people still think that it’s a death sentence to have HIV. This ignorance is a huge problem.
TA Report: Do you think the government of Thailand is giving you the support that you need as a doctor to treat your patients?
Dr. Ananworanich: Yes. Compared to five years ago when I came back from the States, there has been tremendous improvement in a short time. And I think the Division of AIDS and the Global Fund are working very hard to provide support. Right now we have no problem getting first-line treatment. For second-line treatment, there are certain drugs we have access to that aren’t ideal but they can be used. And we’re probably going to get access to free viral load testing as part of the government program pretty soon. So in many regards, we’re very fortunate. As a doctor, it’s very gratifying to be able to make a positive difference.