Characterization of UC781-tenofovir combination gel products for HIV-1 infection prevention in an Ex vivo ectocervical model

Antimicrobial Agents and Chemotherapy

Volumn 56, Issue 6, 2012, Pages 3058-3066

  Cost, Marilyn ^a   Dezzutti, Charlene S ^a,c   Clark, Meredith R ^d   Friend, David R ^d   Akil, Ayman ^a,b   Rohan, Lisa Cencia ^a,b,c  

^a UNIVERSITY OF PITTSBURGH   (United States)

^b UNIVERSITY OF PITTSBURGH   (United States)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^d EASTERN VIRGINIA MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CARBOMER; GLYCEROL; HYDROCHLORIC ACID; HYDROXYPROPYLMETHYLCELLULOSE; METHYL PARABEN; N [4 CHLORO 3 (3 METHYL 2 BUTENYLOXY)PHENYL] 2 METHYL 3 FURANCARBOTHIOAMIDE; PROPYL PARABEN; SODIUM HYDROXIDE; TENOFOVIR PLUS UC781; UNCLASSIFIED DRUG; WATER;

ANTIVIRAL ACTIVITY; AQUEOUS SOLUTION; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFICACY; DRUG FORMULATION; DRUG RELEASE; DRUG SAFETY; EX VIVO STUDY; EXPLANT; FEASIBILITY STUDY; FEMALE; FLOW KINETICS; GEL; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN TISSUE; IN VITRO STUDY; INFECTION PREVENTION; NONHUMAN; PRIORITY JOURNAL; UTERINE CERVIX;

ADENINE; ANILIDES; ANTI-HIV AGENTS; ANTI-RETROVIRAL AGENTS; CERVIX UTERI; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; FEMALE; FURANS; GELS; HIV INFECTIONS; HUMANS; ORGANOPHOSPHONATES; TANDEM MASS SPECTROMETRY;

EID: 84861123517     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.06284-11     Document Type: Article

References (37)

1. Abdool Karim Q, et al. 2010. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329:1168-1174.
2. Abdool Karim SS, et al. 2011. Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women. AIDS 25:957-966.
3. Abner SR, et al. 2005. A human colorectal explant culture to evaluate topical microbicides for the prevention of HIV infection. J. Infect. Dis. 192:1545-1556. (Pubitemid 41504690)
4. Akil, A, et al. 2011. Development and characterization of a vaginal film containing dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), for prevention of HIV-1 sexual transmission. Drug Deliv. Transl. Res. 1:209 -222.
5. Balzarini J, et al. 1996. Highly favorable antiviral activity and resistance profile of the novel thiocarboxanilide pentenyloxy ether derivatives UC-781 and UC-82 as inhibitors of human immunodeficiency virus type 1 replication. Mol. Pharmacol. 50:394-401. (Pubitemid 26265145)
6. Balzarini J, et al. 1998. Preclinical studies on thiocarboxanilide UC-781 as a virucidal agent. AIDS 12:1129-1138. (Pubitemid 28302414)
7. Barnard J, Borkow G, Parniak MA. 1997. The thiocarboxanilide nonnucleoside UC781 is a tight-binding inhibitor of HIV-1 reverse transcriptase. Biochemistry 36:7786-7792. (Pubitemid 27287190)
8. Bauerová, K, Matusova D, Kassai Z. 2001. Chemical enhancers for transdermal drug transport. Eur. J. Drug Metab. Pharmacokinet. 26: 85-94. (Pubitemid 32802400)
9. Borkow G, Salomon H, Wainberg MA, Parniak MA. 2002. Attenuated infectivity of HIV type 1 from epithelial cells pretreated with a tight-binding nonnucleoside reverse transcriptase inhibitor. AIDS Res. Hum. Retroviruses 18:711-714. (Pubitemid 34765339)
10. Carballo-Diéguez A, et al. 2007. Acceptability of tenofovir gel as a vaginal microbicide by US male participants in a phase I clinical trial (HPTN 050). AIDS Care 19:1026-1031.
11. Cranage, M, et al. 2008. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel. PLoS Med. 5:e157.
12. Cummins JE, Jr, et al. 2007. Preclinical testing of candidate topical microbicides for anti-human immunodeficiency virus type 1 activity and tissue toxicity in a human cervical explant culture. Antimicrob. Agents Chemother. 51:1770-1779.
13. D'Cruz OJ, Uckun FM. 2007. Mucosal safety of PHI-443 and stampidine as a combination microbicide to prevent genital transmission of HIV-1. Fertil. Steril. 88(4 Suppl.):1197-1206.
14. Dezzutti CS, et al. 2004. In vitro comparison of topical microbicides for prevention of human immunodeficiency virus type 1 transmission. Antimicrob. Agents Chemother. 48:3834-3844. (Pubitemid 39304612)
15. Feldblum PJ, et al. 2008. SAVVY vaginal gel (C31G) for prevention of HIV infection: a randomized controlled trial in Nigeria. PLoS One 3:e1474.
16. Fernández-Romero JA, et al. 2007. Carrageenan/MIV-150 (PC-815), a combination microbicide. Sex. Transm. Dis. 34:9-14. (Pubitemid 46041501)
17. Fletcher P, et al. 2005. The nonnucleoside reverse transcriptase inhibitor UC-781 inhibits human immunodeficiency virus type 1 infection of human cervical tissue and dissemination by migratory cells. J. Virol. 79: 11179-11186. (Pubitemid 41170659)
18. Fletcher P, et al. 2009. Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor. Antimicrob. Agents Chemother. 53:487-495.
19. Garg AB, Nuttall J, Romano J. 2009. The future of HIV microbicides: challenges and opportunities. Antivir. Chem. Chemother. 19:143-150.
20. Hillier SL, et al. 2005. In vitro and in vivo: the story of nonoxynol 9. J. Acquir. Immune Defic. Syndr. 39:1- 8.
21. Hossain MM, Parniak MA. 2006. In vitro microbicidal activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) UC781 against NNRTI-resistant human immunodeficiency virus type 1. J. Virol. 80: 4440-4446.
22. Johnson TJ, Gupta KM, Fabian J, Albright TH, Kiser PF. 2010. Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir. Eur. J. Pharm. Sci. 39:203-212.
23. Kieweg SL, Katz DF. 2007. Interpreting properties of microbicide drug delivery gels: analyzing deployment kinetics due to squeezing. J. Pharm. Sci. 96:835-850. (Pubitemid 46657872)
24. Kiser PF, et al. 2012. Design of tenofovir/UC781 combination microbicide vaginal gels. J. Pharm. Sci. 101:1852-1864.
25. Liu S, Lu H, Neurath AR, Jiang S. 2005. Combination of candidate microbicides cellulose acetate 1,2-benzenedicarboxylate and UC781 has synergistic and complementary effects against human immunodeficiency virus type 1 infection. Antimicrob. Agents Chemother. 49:1830-1836. (Pubitemid 40631596)
26. Mahalingam A, et al. 2010. Design of a semisolid vaginal microbicide gel by relating composition to properties and performance. Pharm. Res. 27: 2478-2491.
27. Mayer KH, et al. 2006. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS 20:543-551. (Pubitemid 43731598)
28. Motakis D, Parniak MA. 2002. A tight-binding mode of inhibition is essential for anti-human immunodeficiency virus type 1 virucidal activity of nonnucleoside reverse transcriptase inhibitors. Antimicrob. Agents Chemother. 46:1851-1856. (Pubitemid 34535207)
29. Pal R, et al. 2009. Characterization of vaginal transmission of a simian human immunodeficiency virus (SHIV) encoding the reverse transcriptase gene from HIV-1 in Chinese rhesus macaques. Virology 386:102-108.
30. Parikh UM, et al. 2009. Complete protection from repeated vaginal simian-human immunodeficiency virus exposures in macaques by a topical gel containing tenofovir alone or with emtricitabine. J. Virol. 83:10358-10365.
31. Patton DL, et al. 2007. Preclinical safety assessments of UC781 anti-human immunodeficiency virus topical microbicide formulations. Antimicrob. Agents Chemother. 51:1608-1615. (Pubitemid 46744134)
32. Rasool BK, Aziz US, Sarheed O, Rasool AA. 2011. Design and evaluation of a bioadhesive film for transdermal delivery of propranolol hydrochloride. Acta Pharm. 61:271-282.
33. Rohan LC, et al. 2010. In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide. PLoS One 5:e9310.
34. Skoler-Karpoff S, et al. 2008. Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial. Lancet 372:1977-1987.
35. Van Damme L, et al. 2008. Lack of effectiveness of cellulose sulfate gel for the prevention of vaginal HIV transmission. N. Engl. J. Med. 359:463-472.
36. Yang H, Parniak MA, Isaacs CE, Hillier SL, Rohan LC. 2008. Characterization of cyclodextrin inclusion complexes of the anti-HIV non-nucleoside reverse transcriptase inhibitor UC781. AAPS J. 10:606-613.
37. Zussman A, Lara L, Lara HH, Bentwich Z, Borkow G. 2003. Blocking of cell-free and cell-associated HIV-1 transmission through human cervix organ culture with UC781. AIDS 17:653- 661.