Chemoprophylaxis with tenofovir disoproxil fumarate provided partial protection against infection with simian human immunodeficiency virus in macaques given multiple virus challenges.
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.
Subbarao
Shambavi
S
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
Otten
Ronald A
RA
Ramos
Artur
A
Kim
Caryn
C
Jackson
Eddie
E
Monsour
Michael
M
Adams
Debra R
DR
Bashirian
Sheila
S
Johnson
Jeffrey
J
Soriano
Vincent
V
Rendon
Ana
A
Hudgens
Michael G
MG
Butera
Salvatore
S
Janssen
Robert
R
Paxton
Lynn
L
Greenberg
Alan E
AE
Folks
Thomas M
TM
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
D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D054303:HIV Reverse Transcriptase; D000225:Adenine