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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

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Toxicities associated with dual nucleoside reverse-transcriptase inhibitor regimens in HIV-infected children

Russell B Van Dyke1, Lu Wang, Paige L Williams

  • 1Department of Pediatrics, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA. vandyke@tulane.edu

The Journal of Infectious Diseases
|November 13, 2008
PubMed

Insights

In children, zidovudine (ZDV)-containing HIV therapies show fewer clinical toxicities than stavudine (d4T)-based regimens. Other combinations like d4T/3TC, d4T/ddI, and ddI/3TC have similar toxicity profiles suitable for second-line treatment.

Area of Science:

  • Pediatric Infectious Diseases
  • Pharmacology
  • Clinical Toxicology

Background:

  • Nucleoside reverse-transcriptase inhibitors (NRTIs) are a cornerstone of human immunodeficiency virus (HIV) therapy.
  • The specific toxicities of NRTI combinations in pediatric populations are not fully elucidated.

Purpose of the Study:

  • To compare the relative toxicities of five common NRTI pairs in children with vertically acquired HIV infection.
  • To inform optimal NRTI selection for first- and second-line antiretroviral therapy in children.

Main Methods:

  • A cohort of 2233 children (age ≤13 years) with vertically acquired HIV infection receiving at least two NRTIs was analyzed.
  • Incidence rates of clinical and laboratory toxicities were estimated for zidovudine (ZDV)/lamivudine (3TC), ZDV/didanosine (ddI), stavudine (d4T)/3TC, d4T/ddI, and ddI/3TC regimens.
  • Time to first toxicity was compared between NRTI pairs using adjusted hazard ratios.

Main Results:

  • Regimens containing ZDV demonstrated significantly lower rates of clinical toxicities compared to those with d4T (aHR, 0.49; P = .02).
  • Regimens containing ddI showed significantly lower rates of laboratory toxicities than those with 3TC (aHR, 0.78; P = .04).
  • ZDV/3TC had fewer clinical toxicities than d4T/ddI and ddI/3TC, while ZDV/ddI showed fewer clinical toxicities than d4T/3TC.

Conclusions:

  • ZDV-based NRTI regimens are associated with less toxicity in children compared to d4T-based regimens, supporting their use in first-line therapy.
  • The NRTI combinations d4T/3TC, d4T/ddI, and ddI/3TC exhibit comparable toxicity profiles and are suitable for second-line treatment regimens.
Abstract

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