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AZT/3TC & Bactrim interactions
Nov 8, 2001

Dear Dr. In the Pediatric Guidelines, it says that there may be increased toxicity with interactions of AZT and TMP-SMX, and TMP-SMX can increase 3TC blood levels? There seems to be contradiction from various sources concerning taking Bactrim while taking antiretrovirals. For a 6 week old infant who is currently on AZT/3TC and we may be adding Ritonavir or Nelfinavir to the regime depending on viral load levels, not yet known, should we be concerned about all these interactions? Should we hold off on adding the protease inhibitors for 4 to 6 months as it says in the guidelines that it takes this long to reach undectable levels? I am concerned that all these drugs may cause unnecessary toxic side effects. Can you comment please.

Response from Dr. Luzuriaga

Most mother-to-child transmission appears to occur at delivery or after delivery through breast milk. This means that infants at risk can be closely followed to determine their infection status and allows for early intervention should an infant be identified as infected. Most infants have high viral loads over the first 1-2 years of life and viral load or CD4 counts can not be used to predict risk of disease progression in young infants. Current treatment guidelines (See the Treatment Guidelines section of this web site for the Pediatric Treatment Guidelines) therefore recommend the initiation of therapy in infants at diagnosis of HIV infection.

For the bestlong-term outcome, the goal of therapy is maximal suppression of virus and generally at least 3 drugs (2 nucleosides + a protease inhibitor or 2 nucleosides + a non-nucleoside RT inhibitor) are recommended. There are a number of regimens that have been well-tolerated and that have shown good long-term suppression of virus.

I would be somewhat concerned about whether ZDV/3TC alone would suppress viral replication in an infant and would consider using at least 1 more drug. You don't mention whether the baby's mom and the baby had received prophylaxis for mother-to-child transmission and you don't mention the baby's plasma RNA level. These should be taken into account when deciding on a regimen.

In the era prior to the widespread use of potent antiretroviral therapy, pneumocystis carinii pneumonia was one of the most common opportunistic infections. Many infections occurred during the first year of life and CD4 counts during the first year of life did not reliably predict the risk of PCP. The current treatment guidelines therefore recommend the uniform initiation of PCP prophylaxis in HIV-infected infants < 1 year of age and TMP-SMX is the first-line therapy. Some expertshave suggested that PCP prophylaxis might be unnecessary in infants who are diagnosed and treated early (< 1-2 months of age) with potent antiretroviral therapies, providing their viral load becomes undetectable and their CD4 counts remain normal. However, studies to formally evaluate this have not been done.

The most clinically relevant concern regarding the concurrent use of ZDV/3TC and TMP-SMX is the increased risk of lowering the white blood count. However, in infants who begin therapy with normal white blood cell counts, this is relatively uncommon. To minimize this risk, some physicians recommend the use of TMP-SMX regimens that dose TMP-SMX 3 times a week rather than daily.


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