Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides.
BACKGROUND
Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP), a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined.


METHODS
The inhibitory activity of compounds against the X4 virus, HIV-1 IIIB, and the R5 virus, HIV-1 BaL was determined using TZM-bl indicator cells and quantitated by measuring beta-galactosidase induced by infection. The virucidal properties of cellulose acetate 1,2-benzene-dicarboxylate (CAP), the only microbicide provided in water insoluble, micronized form, in the presence of SP was measured.


RESULTS
The HIV-1 inhibitory activity of the polymeric microbicides, poly(naphthalene sulfonate), cellulose sulfate, carrageenan, CAP (in soluble form) and polystyrene sulfonate, respectively, was considerably (range approximately 4 to approximately 73-fold) diminished in the presence of SP (33.3%). Formulations of micronized CAP, providing an acidic buffering system even in the presence of an SP volume excess, effectively inactivated HIV-1 infectivity.


CONCLUSIONS
The data presented here suggest that the in vivo efficacy of polymeric microbicides, acting as HIV-1 entry inhibitors, might become at least partly compromised by the inevitable presence of SP. These possible disadvantages could be overcome by combining the respective polymers with acidic pH buffering systems (built-in for formulations of micronized CAP) or with other anti-HIV-1 compounds, the activity of which is not affected by SP, e.g. reverse transcriptase and zinc finger inhibitors.
Neurath
A Robert
AR
Biochemical Virology Laboratory, The Lindsley F, Kimball Research Institute of the New York Blood Center, New York, NY 10021, USA. arneurath@att.net
Strick
Nathan
N
Li
Yun-Yao
YY
D000282:Administration, Intravaginal; D000813:Anilides / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology; D002460:Cell Line; D002482:Cellulose / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009282:Naphthalenesulfonates / Q000494:pharmacology; D011137:Polystyrenes / Q000494:pharmacology; D012661:Semen; D013854:Thioamides
D000813:Anilides; D019380:Anti-HIV Agents; D005663:Furans; D009282:Naphthalenesulfonates; D011137:Polystyrenes; D013854:Thioamides; C496530:cellulose acetate 1,2-benzenedicarboxylate; C445092:poly(naphthalenesulfonic acid); C003321:polystyrene sulfonic acid; D002351:Carrageenan; D002482:Cellulose; C020254:cellulose sulfate; C100668:UC-781