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4-year old starting meds
Nov 10, 2000

Shortly after my son was born he became very ill and eight months later I learned that we carried the HIV virus. He initially had a viral load of over 3 million and only 2 T-cells. We began him on a regimen of azt/3tc in 1997. After 6 months Dr.s added ritonvir which he was unable to tolerate. Finally went on ddI,d4t and Viracept(current regimen) which he has done wonderfully on until recently. Although he has never been undetectable his viral load has hovered around 30,000 until the last three counts that has shown his viral load has been climbing. It is now 167,000.Although he has a high viral load his cd-4 has been strong for over 3 years,never below 1,800 and currently is at 2,130.Genotype testing says he is resistant to Azt, Abacavir but not DDI, d4t. I have a couple of questions. His Dr. is suggesting we go on 4 drugs -- maybe Amprenavir,sustiva and 3tc and another nuke, not sure which one just yet. Are these drugs optimal and safe in your opinion? He is a 4 year old little boy and treating him with so many potent drugs with possible serious side-effects is very frightening.Are there better medicines in the pipeline that I should search for or hold out for? Why not just three new drugs? My husband wants to take him out of state to a children's research hospital. I am not sure that is the best place to go for a second opinion. Does a research hospital have access to drugs that our local Dr. does not? I appreciate any wisdom you can give me and value your opinion. Thank You

Response from Dr. Luzuriaga

You raise several good questions. Your first pertains to the advisability of switching antiviral medications in your 4 year old son who has been clinically well with a stable (normal for age) CD4 count but an increasing plasma viral load (now 167,000). When children's viral load increases on a regimen, we ask the following questions to try to understand why: 1) Has the child received all medications according to the recommended schedule? Increases in RNA can be seen when adherence is incomplete ; 2) Is the increase in RNA a reflection of resistance to the current medications?

If RNA is elevated despite good adherence, we begin to think about changing meds. As Dr. Pavia has pointed out (See his answer in the Treatment Forum), when to switch drugs is a balancing act and we often do not switch drugs when the RNA is detectable but low. However, several studies have documented a strong correlation between plasma RNA and disease progression in children; the risk of disease progression in children increases particularly with plasma RNA over 100,000 (Mofenson et al, Journal of Infectious Diseases 175:1029-1038, 1997). So, I would strongly consider switching antiretroviral therapy in your child if a repeat plasma RNA is over 100,000.

The next question then becomes what your child's options are in terms of therapy. In children who have experienced several drug combinations, we often obtain a resistance profile, as your doctor has done. You mention that your son has been on 3TC in the past and that a mutation to abacavir has been detected. Since some mutations are associated with abacavir and 3TC cross-resistance, I would want to clarify the resistance profile. That said, it seems as if your child has several available options, including non-nucleoside reverse transcriptase inhibitors and protease inhibitors. In general, I would recommend a 4 drug regimen, since we would want to maximize our chances of controlling viral replication. However, final choice of drugs would depend on clarification of the resistance profile, whether your son can take pills, your son's schedule (e.g., does he attend school or day care), and access to investigational agents or drug combinations through clinical trials. For this reason, I would recommend that you discuss things again with your care provider. I also think that it's a good idea to seek a second opinion, if possible, from a pediatric expert who cares for many HIV infected children. As Dr. Pavia has pointed out, most physicians want their patients to be well-informed regarding their choices and welcome second opinions. If you let us know where you are (or could travel to), we could suggest the names of some individuals.

You ask whether antivirals are optimal and safe for children. We've learned over the years that children's metabolism of the antivirals differ from adults' and thus children often require different dosing. Antivirals have been generally well-tolerated, but each antiviral has its own safety profile and it's important that you go over these with your doctor.

Please don't hesitate to write if you have further questions.

KL

Katherine Luzuriaga, M.D.


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