Two low doses of tenofovir protect newborn macaques against oral simian immunodeficiency virus infection.
Simple affordable interventions are needed to reduce vertical human immunodeficiency virus (HIV) transmission in developing countries. The efficacy of 2 low doses (4 mg/kg, subcutaneously) or 1 high dose (30 mg/kg, subcutaneously) of the reverse-transcriptase inhibitor 9-[2-(phosphonomethoxy)propyl]adenine (PMPA; tenofovir) to protect newborn macaques against simian immunodeficiency virus (SIV) infection was investigated. Thirteen newborn macaques were inoculated orally with virulent SIVmac251. The 4 placebo-treated animals (group A) became persistently infected. Groups B and C (n=4 in each group) received 2 4-mg/kg doses of PMPA, either 4 h before and 20 h after (group B) or 1 and 25 h after SIV inoculation (group C). One animal (group D) received a single 30-mg/kg dose of PMPA 1 h after SIV inoculation. Despite evidence of an initial transient infection, 3 group B animals, 2 group C animals, and the group D animal were SIV negative and seronegative at ages 19-23 months. Immune activation with recall antigens or pharmacologic immunosuppression with corticosteroids failed to reactivate viral replication. These data suggest that 1 or 2 doses of PMPA may protect human newborns against intrapartum HIV infection.
Van Rompay
K K
KK
California Regional Primate Research Center, University of California, Davis, CA 95616-8542, USA. kkvanrompay@ucdavis.edu
McChesney
M B
MB
Aguirre
N L
NL
Schmidt
K A
KA
Bischofberger
N
N
Marthas
M L
ML
D000225:Adenine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000914:Antibodies, Viral / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D006801:Humans; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D011533:Proviruses; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity / Q000502:physiology; D000068698:Tenofovir
D019380:Anti-HIV Agents; D000914:Antibodies, Viral; D004279:DNA, Viral; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine