The Clinical Benefits of Tenofovir for Simian Immunodeficiency Virus-Infected Macaques Are Larger Than Predicted by Its Effects on Standard Viral and Immunologic Parameters

J Acquir Immune Defic Syndr. 2004 Aug 1;36(4):900-14. doi: 10.1097/00126334-200408010-00003.

Abstract

Previous studies have demonstrated that tenofovir (9-[2-(phosphonomethoxy)propyl]adenine; PMPA) treatment is usually very effective in suppressing viremia in macaques infected with simian immunodeficiency virus (SIV). The present study focuses on a subset of infant macaques that were chronically infected with highly virulent SIVmac251, and for which prolonged tenofovir treatment failed to significantly suppress viral RNA levels in plasma despite the presence of tenofovirsusceptible virus at the onset of therapy. While untreated animals with similarly high viremia developed fatal immunodeficiency within 3-6 months, these tenofovir-treated animals had significantly improved survival (up to 3.5 years). This clinical benefit occurred even in animals for which tenofovir had little or no effect on CD4 and CD8 lymphocyte counts and antibody responses to SIV and test antigens. Thus, the clinical benefits of tenofovir were larger than predicted by plasma viral RNA levels and other routine laboratory parameters.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Animals
  • Animals, Newborn
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use*
  • Antibodies, Viral / blood
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Chronic Disease
  • Drug Evaluation, Preclinical
  • Female
  • Injections, Subcutaneous
  • Lymphocyte Count
  • Macaca mulatta
  • Male
  • Organophosphonates / administration & dosage
  • Organophosphonates / therapeutic use*
  • Simian Acquired Immunodeficiency Syndrome / blood
  • Simian Acquired Immunodeficiency Syndrome / drug therapy*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus* / immunology
  • Survival Analysis
  • Tenofovir
  • Viral Load

Substances

  • Anti-HIV Agents
  • Antibodies, Viral
  • Organophosphonates
  • Tenofovir
  • Adenine