Cellulose acetate 1,2-benzenedicarboxylate protects against challenge with pathogenic X4 and R5 simian/human immunodeficiency virus.
OBJECTIVE
To evaluate the protective efficacy of cellulose acetate 1,2-benzenedicarboxylate (CAP) formulated in a glycerol-based gel against infection with CXCR4 (X4) and CCR5 (R5) viruses in the simian/human immunodeficiency virus (SHIV)/rhesus macaque model of HIV-1 transmission.


METHODS
Mucosal infection of non-human primates is a reasonable model for use in the investigation of HIV-1 intervention strategies.


METHODS
Rhesus macaques treated with Depo-Provera 5 weeks prior to challenge were inoculated intravaginally twice, over a period of 6 h with mixed inocula of pathogenic X4- and R5-SHIV in the presence or absence of CAP. Plasma viral load, peripheral and mucosal CD4 T cell counts as well as the genotype of the circulating virus were determined.


RESULTS
CAP protected seven of ten macaques against transmission of both X4- and R5-SHIV, reaching statistically significant values (P = 0.0256). Delayed and/or reduced virus replication, as well as blunting of peripheral and mucosal CD4 T cell loss was noted in the three macaques that were infected in the CAP treated group compared to those in the placebo group. Further, protection conferred by CAP appeared to be more effective against X4- than R5-SHIV infection.


CONCLUSIONS
CAP is protective against highly permissive challenges with X4 and R5 viruses in vivo. Research on further development of this promising compound as a candidate microbicide for the prevention of sexual HIV-1 transmission is therefore warranted.
Boadi
Tina
T
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
Schneider
Eric
E
Chung
Stephen
S
Tsai
Lily
L
Gettie
Agegnehu
A
Ratterree
Marion
M
Blanchard
James
J
Neurath
A Robert
AR
Cheng-Mayer
Cecilia
C
D000282:Administration, Intravaginal; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002482:Cellulose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005260:Female; D018928:Immunity, Mucosal; D008253:Macaca mulatta; D011374:Progesterone / Q000494:pharmacology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D019562:Viral Load; D014779:Virus Replication
D019380:Anti-HIV Agents; C496530:cellulose acetate 1,2-benzenedicarboxylate; D011374:Progesterone; D002482:Cellulose