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

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 nuclear. 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.

• Authors: K K Van Rompay, J M Cherrington, M L Marthas, C J Berardi, A S Mulato, A Spinner, R P Tarara, D R Canfield, S Telm, N Bischofberger, N C Pedersen
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 40 Issue 11 Pg. 2586-91 (Nov 1996) ISSN: 0066-4804 [Print] United States
• PMID: 8913470 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-HIV Agents
• Antibodies, Viral
• Immunoglobulin G
• Organophosphonates
• Organophosphorus Compounds
• Tenofovir
• Adenine

Topics

• Adenine (adverse effects, analogs & derivatives, therapeutic use)
• Animals
• Animals, Newborn
• Anti-HIV Agents (adverse effects, therapeutic use)
• Antibodies, Viral (analysis)
• Drug Resistance
• Immunoglobulin G (analysis)
• Macaca mulatta
• Microbial Sensitivity Tests
• Organophosphonates
• Organophosphorus Compounds (adverse effects, therapeutic use)
• Phenotype
• Simian Acquired Immunodeficiency Syndrome (drug therapy, virology)
• Simian Immunodeficiency Virus
• T-Lymphocytes (virology)
• Tenofovir