title: Chemoprophylaxis with tenofovir disoproxil fumarate provided partial protection against infection with simian human immunodeficiency virus in macaques given multiple virus challenges.
abstract: We examined the efficacy of tenofovir disoproxil fumarate (TDF) in blocking simian human immunodeficiency virus (SHIV) infection in Chinese rhesus macaques. Once weekly for 14 weeks or until a macaque became infected, 12 male macaques were inoculated intrarectally with amounts of SHIV(SF162P3) (10 median tissue culture infective doses; 3.8 x 10(5) virus particles) that were approximately 5-fold higher than the human immunodeficiency virus type 1 RNA levels noted in human semen during an acute infection. Of the 12 macaques, 4 received oral TDF daily, 4 received oral TDF once weekly, and 4 (control animals) received no TDF. The control animals became infected after receiving a median of 1.5 virus inoculations; macaques receiving TDF daily (1 macaque remained uninfected after 14 inoculations) and those receiving TDF weekly became infected after a median duration of 6.0 and 7.0 weeks, respectively. Although infection was delayed in treated macaques, compared with control macaques, the differences were not statistically significant (P=.315); however, the study was limited by the small numbers of animals evaluated and the variability in blood levels of TDF that resulted from oral dosing. These data demonstrate that treatment with oral TDF provided partial protection against SHIV infection but ultimately did not protect all TDF treated animals against multiple virus challenges.
authors.affiliation: Division of HIV/AIDS Prevention, National Center for HIV, STD, & TB Prevention, National Center for Infectious Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. sfs2@cdc.gov
authors.forename: Shambavi
authors.initials: S
authors.lastname: Subbarao
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Otten
authors.forename: Artur
authors.initials: A
authors.lastname: Ramos
authors.forename: Caryn
authors.initials: C
authors.lastname: Kim
authors.forename: Eddie
authors.initials: E
authors.lastname: Jackson
authors.forename: Michael
authors.initials: M
authors.lastname: Monsour
authors.forename: Debra R
authors.initials: DR
authors.lastname: Adams
authors.forename: Sheila
authors.initials: S
authors.lastname: Bashirian
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Johnson
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Ana
authors.initials: A
authors.lastname: Rendon
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hudgens
authors.forename: Salvatore
authors.initials: S
authors.lastname: Butera
authors.forename: Robert
authors.initials: R
authors.lastname: Janssen
authors.forename: Lynn
authors.initials: L
authors.lastname: Paxton
authors.forename: Alan E
authors.initials: AE
authors.lastname: Greenberg
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Folks
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018890:Chemoprevention; D004195:Disease Models, Animal; D024882:Drug Resistance, Viral / Q000235:genetics; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D054303:HIV Reverse Transcriptase; D000225:Adenine