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Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal.

Publication ,  Journal Article
Van Rompay, KKA; Trott, KA; Jayashankar, K; Geng, Y; LaBranche, CC; Johnson, JA; Landucci, G; Lipscomb, J; Tarara, RP; Canfield, DR; Heneine, W ...
Published in: Retrovirology
July 17, 2012

BACKGROUND: We reported previously that while prolonged tenofovir monotherapy of macaques infected with virulent simian immunodeficiency virus (SIV) resulted invariably in the emergence of viral mutants with reduced in vitro drug susceptibility and a K65R mutation in reverse transcriptase, some animals controlled virus replication for years. Transient CD8+ cell depletion or short-term tenofovir interruption within 1 to 5 years of treatment demonstrated that a combination of CD8+ cell-mediated immune responses and continued tenofovir therapy was required for sustained suppression of viremia. We report here follow-up data on 5 such animals that received tenofovir for 8 to 14 years. RESULTS: Although one animal had a gradual increase in viremia from 3 years onwards, the other 4 tenofovir-treated animals maintained undetectable viremia with occasional viral blips (≤ 300 RNA copies/ml plasma). When tenofovir was withdrawn after 8 to 10 years from three animals with undetectable viremia, the pattern of occasional episodes of low viremia (≤ 3600 RNA/ml plasma) continued throughout the 10-month follow-up period. These animals had low virus levels in lymphoid tissues, and evidence of multiple SIV-specific immune responses. CONCLUSION: Under certain conditions (i.e., prolonged antiviral therapy initiated early after infection; viral mutants with reduced drug susceptibility) a virus-host balance characterized by strong immunologic control of virus replication can be achieved. Although further research is needed to translate these findings into clinical applications, these observations provide hope for a functional cure of HIV infection via immunotherapeutic strategies that boost antiviral immunity and reduce the need for continuous antiretroviral therapy.

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Published In

Retrovirology

DOI

EISSN

1742-4690

Publication Date

July 17, 2012

Volume

9

Start / End Page

57

Location

England

Related Subject Headings

  • Virus Replication
  • Virology
  • Viremia
  • Treatment Outcome
  • Time Factors
  • Tenofovir
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • RNA-Directed DNA Polymerase
 

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Van Rompay, K. K. A., Trott, K. A., Jayashankar, K., Geng, Y., LaBranche, C. C., Johnson, J. A., … Abel, K. (2012). Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Retrovirology, 9, 57. https://doi.org/10.1186/1742-4690-9-57
Van Rompay, Koen K. A., Kristin A. Trott, Kartika Jayashankar, Yongzhi Geng, Celia C. LaBranche, Jeffrey A. Johnson, Gary Landucci, et al. “Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal.Retrovirology 9 (July 17, 2012): 57. https://doi.org/10.1186/1742-4690-9-57.
Van Rompay KKA, Trott KA, Jayashankar K, Geng Y, LaBranche CC, Johnson JA, Landucci G, Lipscomb J, Tarara RP, Canfield DR, Heneine W, Forthal DN, Montefiori D, Abel K. Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Retrovirology. 2012 Jul 17;9:57.
Journal cover image

Published In

Retrovirology

DOI

EISSN

1742-4690

Publication Date

July 17, 2012

Volume

9

Start / End Page

57

Location

England

Related Subject Headings

  • Virus Replication
  • Virology
  • Viremia
  • Treatment Outcome
  • Time Factors
  • Tenofovir
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • RNA-Directed DNA Polymerase