AEGiS-15IAC: [LbOrB10] ORAL TENOFOVIR DF PROTECTS INFANT MACAQUES AGAINST INFECTION FOLLOWING REPEATED LOW-DOSE ORAL EXPOSURE TO VIRULENT SIMIAN IMMUNODEFICIENCY VIRUS

15th International AIDS Conference

Bangkok, Thailand — July 11-July 16, 2004

[LbOrB10] ORAL TENOFOVIR DF PROTECTS INFANT MACAQUES AGAINST INFECTION FOLLOWING REPEATED LOW-DOSE ORAL EXPOSURE TO VIRULENT SIMIAN IMMUNODEFICIENCY VIRUS

Int Conf AIDS. 2004 Jul 11-16;15:Abstract No. LbOrB10

K Van Rompay¹, J Lawson¹, R Colón¹, N Bischofberger², M Marthas¹
¹University of California, Davis, United States; ²Gilead Sciences, Foster City, United States

BACKGROUND: There is a need for effective strategies to prevent mother-to-infant HIV transmission during breast-feeding in developing countries. To mimic the multiple exposures to HIV that occur during prolonged breast-feeding, we have developed an animal model in which infant macaques are bottle-fed repeatedly low doses of virulent simian immunodeficiency virus (SIVmac251). We tested the efficacy of tenofovir disoproxil fumarate (tenofovir DF) in this animal model, using the same pediatric formulation and equivalent regimen as that used to treat human infants.

METHODS: Infant macaques were exposed orally to low doses of virulent SIVmac251 during 2 inoculation periods: during the first week of life and for animals that were still uninfected, again at 1 month of age. Each SIV inoculation period consisted of 15 feedings (3 times per day for 5 consecutive days). One group of animals received oral tenofovir DF syrup at a dose (10 mg/kg once daily) estimated to be pharmacokinetically equivalent (based on area-under-the-curve values) to the 8 mg/kg regimen used in pediatric trials, and the 300 mg tenofovir DF tablet given to adults. Tenofovir DF was given once daily starting one day before until one day after each SIV inoculation period.

RESULTS: After the 2 rounds of virus inoculations, 20 of 22 untreated infant macaques were persistently viremic. In contrast, 3 of 6 tenofovir-treated animals were uninfected at 3 months of age (p=0.05; two-sided Fisher’s Exact test). We are currently testing in additional animals if a longer post-exposure treatment will further reduce infection rates.

CONCLUSIONS: These data suggest that tenofovir DF administration will be effective to protect infants against HIV transmission from breast-milk. Our data provide also support for the ongoing trials in which the use of chronic tenofovir DF administration is investigated to reduce infection rates among high-risk adult groups (commercial sex workers, and men having sex with men).

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