9-[2-(phosphonomethoxy)propyl]adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques

Koen K.A. Van Rompay, Julie M. Cherrington, Marta Marthas, Christopher J. Berardi, Andrew S. Mulato, Abbie Spinner, Ross P. Tarara, Don R. Canfield, Stephan Telm, Norbert Bischofberger, Niels C Pedersen

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Abstract

The long-term therapeutic and toxic effects of 9-[2- (phosphonomethoxy)propyl]adenine (PMPA) were evaluated in simian immunodeficiency virus (SIV)-infected newborn rhesus macaques. Four untreated SIV-infected newborn macaques developed persistently high levels of viremia, and three of the four animals had rapidly fatal disease within 3 months. In contrast, long-term PMPA treatment of four newborn macaques starting 3 weeks after virus inoculation resulted in a rapid, pronounced, and persistent reduction of viremia in three of the four animals. Emergence of virus with fivefold-decreased susceptibility to PMPA occurred in all four PMPA-treated animals and was associated with the development of a lysine-to-arginine substitution at amino acid 65 (K65R mutation) and additional mutations in the reverse transcriptase; however, the clinical implications of this low-level drug resistance are unclear. No toxic side effects have been seen, and all PMPA-treated animals have remained disease- free for more than 13 months. Our data suggest that PMPA holds much promise for the treatment of human immunodeficiency virus-infected human infants and adults.

Original languageEnglish (US)
Pages (from-to)2586-2591
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume40
Issue number11
StatePublished - Nov 1996

Fingerprint

Simian Immunodeficiency Virus
Adenine
Virus Diseases
Macaca mulatta
Poisons
Viremia
Macaca
Therapeutics
Viruses
Mutation
RNA-Directed DNA Polymerase
Therapeutic Uses
Amino Acid Substitution
Drug Resistance
Lysine
Arginine
HIV

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

9-[2-(phosphonomethoxy)propyl]adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques. / Van Rompay, Koen K.A.; Cherrington, Julie M.; Marthas, Marta; Berardi, Christopher J.; Mulato, Andrew S.; Spinner, Abbie; Tarara, Ross P.; Canfield, Don R.; Telm, Stephan; Bischofberger, Norbert; Pedersen, Niels C.

In: Antimicrobial Agents and Chemotherapy, Vol. 40, No. 11, 11.1996, p. 2586-2591.

Research output: Contribution to journalArticle

Van Rompay, KKA, Cherrington, JM, Marthas, M, Berardi, CJ, Mulato, AS, Spinner, A, Tarara, RP, Canfield, DR, Telm, S, Bischofberger, N & Pedersen, NC 1996, '9-[2-(phosphonomethoxy)propyl]adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques', Antimicrobial Agents and Chemotherapy, vol. 40, no. 11, pp. 2586-2591.
Van Rompay, Koen K.A. ; Cherrington, Julie M. ; Marthas, Marta ; Berardi, Christopher J. ; Mulato, Andrew S. ; Spinner, Abbie ; Tarara, Ross P. ; Canfield, Don R. ; Telm, Stephan ; Bischofberger, Norbert ; Pedersen, Niels C. / 9-[2-(phosphonomethoxy)propyl]adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques. In: Antimicrobial Agents and Chemotherapy. 1996 ; Vol. 40, No. 11. pp. 2586-2591.
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