Structured treatment interruptions with tenofovir monotherapy for simian immunodeficiency virus-infected newborn macaques

Koen K.A. Van Rompay, Raman P. Singh, Walid Heneine, Jeffrey A. Johnson, David C. Montefiori, Norbert Bischofberger, Marta Marthas

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

We demonstrated previously that prolonged tenofovir treatment of infant macaques, starting early during infection with virulent simian immunodeficiency virus (SIVmac251), can lead to persistently low or undetectable viremia even after the emergence of mutants with reduced in vitro susceptibility to tenofovir as a result of a K65R mutation in reverse transcriptase; this control of viremia was demonstrated to be mediated by the generation of effective antiviral immune responses. To determine whether structured treatment interruptions (STI) can induce similar immunologic control of viremia, eight newborn macaques were infected with highly virulent SIVmac251 and started on a tenofovir STI regimen 5 days later. Treatment was withdrawn permanently at 33 weeks of age. All animals receiving STI fared much better than 22 untreated SIVmac251-infected infant macaques. However, there was a high variability among animals in the viral RNA set point after complete drug withdrawal, and none of the animals was able to achieve long-term immunologic suppression of viremia to persistently low levels. Early immunologic and viral markers in blood (including the detection of the K65R mutation) were not predictive of the viral RNA set point after drug withdrawal. These results, which reflect the complex interactions between drug resistance mutations, viral virulence, and drug- and immune-mediated inhibition of virus replication, highlight the difficulties associated with trying to develop STI regimens with predictable efficacy for clinical practice.

Original languageEnglish (US)
Pages (from-to)6399-6410
Number of pages12
JournalJournal of Virology
Volume80
Issue number13
DOIs
StatePublished - Jul 1 2006

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Van Rompay, K. K. A., Singh, R. P., Heneine, W., Johnson, J. A., Montefiori, D. C., Bischofberger, N., & Marthas, M. (2006). Structured treatment interruptions with tenofovir monotherapy for simian immunodeficiency virus-infected newborn macaques. Journal of Virology, 80(13), 6399-6410. https://doi.org/10.1128/JVI.02308-05