Combination of candidate microbicides cellulose acetate 1,2-benzenedicarboxylate and UC781 has synergistic and complementary effects against human immunodeficiency virus type 1 infection.
The combination of two candidate microbicides, cellulose acetate 1,2-benzenedicarboxylate (CAP), a polymer that blocks human immunodeficiency virus type 1 (HIV-1) entry by targeting gp120 and gp41, and UC781, a tight-binding HIV-1 reverse transcriptase inhibitor (RTI), resulted in effective synergy for inhibition of MT-2 cell infection by HIV-1(IIIB), a laboratory-adapted virus strain. The 95% effective concentration values for the combination were reduced about 15- to 20-fold compared with those corresponding to the single compounds. The combination of CAP and UC781 is also synergistic in inhibiting infection of peripheral blood mononuclear cells by a primary HIV-1 isolate, 92US657. Combinations of CAP with other RTIs, such as efavirenz or zidovudine, also had significant synergistic effects on the inhibition of HIV-1 infection. In addition, CAP and UC781 had complementary effects against HIV-1 infection since (i) CAP inhibited infection by the UC781-resistant strain HIV-1(IIIB) A17 and (ii) pretreatment of MT-2 cells with UC781, but not CAP, abolished subsequent infection after removal of the compound. This suggests that the combination of CAP and UC781 represents a promising candidate microbicide for prevention of sexual transmission of HIV-1.
Liu
Shuwen
S
Lindsley F. Kimball Research Institute, New York Blood Center, 310 E 67th St., New York, NY 10021, USA.
Lu
Hong
H
Neurath
A Robert
AR
Jiang
Shibo
S
D000813:Anilides / Q000494:pharmacology*; D019380:Anti-HIV Agents; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002482:Cellulose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004357:Drug Synergism; D005663:Furans / Q000494:pharmacology*; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D013854:Thioamides
D000813:Anilides; D019380:Anti-HIV Agents; D005663:Furans; D016655:HIV Core Protein p24; D013854:Thioamides; C496530:cellulose acetate 1,2-benzenedicarboxylate; D002482:Cellulose; C100668:UC-781