Topical administration of low-dose tenofovir disoproxil fumarate to protect infant macaques against multiple oral exposures of low doses of simian immunodeficiency virus.
Simian immunodeficiency virus (SIV) infection of infant macaques is a useful animal model to determine whether topical (oral) administration of antiviral compounds to the nursing infant could reduce human immunodeficiency virus transmission through breast-feeding. The reverse-transcriptase inhibitor tenofovir was selected because of previous demonstrations that systemic drug levels are effective in preventing SIV infection. To mimic the multiple exposures to virus during breast-feeding, 14 infant macaques were fed 15 low doses of SIVmac251 without chemical restraint. Six animals were treated with placebo, and 2 groups of 4 animals received oral topical doses of tenofovir disoproxil fumarate (DF; equivalent to 0.037 mg of tenofovir/day). About half the animals of each group became infected. In a subsequent study, 2 oral inoculations of 4 juvenile macaques with a mixture of tenofovir DF and SIVmac251 induced persistent infection. Topical administration of low doses of tenofovir DF did not protect against oral SIV infection.
Van Rompay
Koen K A
KK
California National Primate Research Center, University of California, Davis, California 95616-8542, USA. kkvanrompay@ucdavis.edu
Schmidt
Kimberli A
KA
Lawson
Jonathan R
JR
Singh
Raman
R
Bischofberger
Norbert
N
Marthas
Marta L
ML
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000287:Administration, Topical; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D008251:Macaca; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000472:pathogenicity; D000068698:Tenofovir
D019380:Anti-HIV Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D000068698:Tenofovir; D000225:Adenine