An algorithm for the preclinical development of anti-HIV topical microbicides

Current HIV Research

Volumn 10, Issue 1, 2012, Pages 97-104

  Buckheit, Robert W ^a   Buckheit, Karen W ^a  

^a ImQuest Biosciences   (United States)

Author keywords

Efficacy; HIV 1; Microbicide; Pharmacokinetics; Preclinical; Prevention; Resistance; Toxicity

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; ANTIINFECTIVE AGENT; ANTIVIRUS AGENT; C31G; CARBOPOL 974P; CARRAGEENAN; CELLULOSE SULFATE; CYANOVIRIN N; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; IQP 0410; IQP 0528; IQP 1187; MICROBICIDE; N [4 CHLORO 3 (3 METHYL 2 BUTENYLOXY)PHENYL] 2 METHYL 3 FURANCARBOTHIOAMIDE; NONOXINOL 9; PRO 2000; SAVVY; TENOFOVIR; UNCLASSIFIED DRUG;

ALGORITHM; ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; ARTICLE; CD4 LYMPHOCYTE COUNT; DRUG APPROVAL; DRUG CONTROL; DRUG CYTOTOXICITY; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG FORMULATION; DRUG LEGISLATION; DRUG MECHANISM; DRUG SAFETY; DRUG SCREENING; EX VIVO STUDY; FOOD AND DRUG ADMINISTRATION; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFECTION PREVENTION; INSTRUMENT STERILIZATION; NONHUMAN; RECTUM; SEMINAL PLASMA; SEXUAL TRANSMISSION; SEXUALLY TRANSMITTED DISEASE; UTERINE CERVIX CYTOLOGY; VAGINA; VIRUS INFECTIVITY; VIRUS REPLICATION; VIRUS TRANSMISSION;

EID: 84857136316     PISSN: 1570162X     EISSN: 18734251     Source Type: Journal    
DOI: 10.2174/157016212799304698     Document Type: Article

References (54)

1. UNAIDS, UNAIDS Report on the Global AIDS Epidemic 2010. 2010.
2. Fischl MA, Richman DD, Grieco MH, et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med 1987; 317(4): p. 185-191.
3. Bonfanti P, Capetti A, Rizzardini G. HIV disease treatment in the era of HAART. Biomed Pharmacother 1999; 53(2): 93-105.
4. Yeni, PG, Hammer SM, Hirsch MS, et al. Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA Panel. JAMA, 2004; 292(2): p. 251-265.
5. Carpenter, CC, Cooper DA, Fischl MA, et al. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA 2000; 283(3): 381-390.
6. Richman DD, HIV therapeutics. Science 1996; 272(5270): 1886-1888.
7. Trabattoni D, Lo-Caputo S, Biasin M, et al. Modulation of human immunodeficiency virus (HIV)-specific immune response by using efavirenz, nelfinavir, and stavudine in a rescue therapy regimen for HIV-infected, drug-experienced patients. Clin Diagn Lab Immunol 2002; 9(5): 1114-1118.
8. Coombs, RW, Speck CE, Hughes JP, et al. Association between culturable human immunodeficiency virus type 1 (HIV-1) in semen and HIV-1 RNA levels in semen and blood: evidence for compartmentalization of HIV-1 between semen and blood. J Infect Dis 1998; 177(2): 320-330.
9. Gupta PJ, Mellors L, Kingsley E, et al. High viral load in semen of human immunodeficiency virus type 1-infected men at all stages of disease and its reduction by therapy with protease and nonnucleoside reverse transcriptase inhibitors. J Virol 1997; 71(8): 6271-6275.
10. Quayle AJ, Xu C, Mayer KH, et al. T lymphocytes and macrophages, but not motile spermatozoa, are a significant source of human immunodeficiency virus in semen. J Infect Dis 1997; 176(4): 960-968.
11. Alexander NJ, Baker E, Kaptein M, et al. Why consider vaginal drug administration? Fertil Steril 2004; 82(1): 1-12.
12. Forsberg JG. A morphologist's approach to the vagina. Acta Obstet Gynecol Scand Suppl 1996; 163: 3-10.
13. Miller CJ. HIV transmission: migratory Langerhans cells are primary targets in vaginal HIV transmission. Immunol Cell Biol 2007; 85(4): 269-270.
14. Cole AM. Innate host defense of human vaginal and cervical mucosae. Curr Top Microbiol Immunol 2006; 306: 199-230.
15. Miller CJ, Li Q, Abel K, et al. Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J Virol 2005; 79(14): 9217-9227.
16. Haase AT. Perils at mucosal front lines for HIV and SIV and their hosts. Nat Rev Immunol 2005; 45(10): 783-792.
17. Pope M, Haase AT. Transmission, acute HIV-1 infection and the quest for strategies to prevent infection. Nat Med 2003; 9(7): 847-852.
18. Zhang Z, Schuler T, Zupancic M, et al. Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science 1999; 286(5443): 1353-1357.
19. Turpin JA. Topical microbicides to prevent the transmission of HIV: formulation gaps and challenges. Drug Deliv Transl Res 2011; 1(3): 194-200.
20. Buckheit RW, Watson KM Jr., Morrow KM, et al. Development of topical microbicides to prevent the sexual transmission of HIV. Antiviral Res 2010; 85(1): 142-158.
21. Abdool Karim SS. Results of effectiveness trials of PRO 2000 gel: lessons for future microbicide trials. Future Microbiol 2010; 5(4): 527-529.
22. Morris GC, Lacey CJ. Microbicides and HIV prevention: lessons from the past, looking to the future. Curr Opin Infect Dis 2010; 23(1): 57-63.
23. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010; 329(5996): 1168-1174.
24. Garg AB, J Nuttall, Romano J. The future of HIV microbicides: challenges and opportunities. Antivir Chem Chemother 2009; 19(4): 143-50.
25. Hladik F, Doncel GF. Preventing mucosal HIV transmission with topical microbicides: challenges and opportunities. Antiviral Res 2010; 88 Suppl 1: S3-S9.
26. Kelly CG, Shattock RJ. Specific Microbicides in the Prevention of HIV Infection. J Intern Med 2011.
27. Lackman-Smith C, Osterling C, Luckenbaugh K, et al, Development of a comprehensive human immunodeficiency virus type 1 screening algorithm for discovery and preclinical testing of topical microbicides. Antimicrob Agents Chemother 2008; 52(5): p. 1768-1781.
28. Administration, T.F.a.D., Guidance for Industry for Antiviral Product Development. 2006.
29. Doncel GF, Clark MR. Preclinical evaluation of anti-HIV microbicide products: New models and biomarkers. Antiviral Res 2010; 88 Suppl 1: S10-S18.
30. Lard-Whiteford SL, Matecka D, O'Rear JJ, et al. Recommendations for the nonclinical development of topical microbicides for prevention of HIV transmission: an update. J Acquir Immune Defic Syndr 2004; 36(1): 541-552.
31. Mauck C, Rosenberg Z, Van Damme L. Recommendations for the clinical development of topical microbicides: an update. AIDS 2001; 15(7): 857-868.
32. Turpin JA. Considerations and development of topical microbicides to inhibit the sexual transmission of HIV. Expert Opin Investig Drugs 2002; 11(8): 1077-1097.
33. Keller MJ, Herold BC. Understanding basic mechanisms and optimizing assays to evaluate the efficacy of vaginal microbicides. Sex Transm Dis 2009; 36(3 Suppl): S92-S95.
34. Woodsong C. Covert use of topical microbicides: implications for acceptability and use. Perspect Sex Reprod Health 2004; 36(3): 127-131.
35. Morner A, Bjorndal A, Albert J, et al. Primary human immunodeficiency virus type 2 (HIV-2) isolates, like HIV-1 isolates, frequently use CCR5 but show promiscuity in coreceptor usage. J Virol 1999; 73(3): 2343-2349.
36. Takeuchi Y, McClure MO, Pizzato M. Identification of gammaretroviruses constitutively released from cell lines used for human immunodeficiency virus research. J Virol 2008; 82(24): 12585-12588.
37. Fichorova RN, Anderson DJ. Differential expression of immunobiological mediators by immortalized human cervical and vaginal epithelial cells. Biol Reprod 1999; 60(2): 508-514.
38. Fichorova RN, Desai PJ, Gibson FC, 3rd, et al. Distinct proinflammatory host responses to Neisseria gonorrhoeae infection in immortalized human cervical and vaginal epithelial cells. Infect Immun 2001; 69(9): 5840-5848.
39. Fichorova RN, Tucker LD, Anderson DJ. The molecular basis of nonoxynol-9-induced vaginal inflammation and its possible relevance to human immunodeficiency virus type 1 transmission. J Infect Dis 2001; 184(4): 418-428.
40. Herold BC, Mesquita PM, Madan RP, et al. Female genital tract secretions and semen impact the development of microbicides for the prevention of HIV and other sexually transmitted infections. Am J Reprod Immunol 2011; 65(3): 325-333.
41. Kim KA, Yolamanova M, Zirafi O, et al. Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI. Retrovirology 2010; 7: 55.
42. Quayle AJ, Coston W M, Trocha AK, et al. Detection of HIV-1- specific CTLs in the semen of HIV-infected individuals. J Immunol, 1998; 161(8): 4406-4410.
43. Balzarini J, Karlsson A, Perez-Perez MJ, et al. Knocking-out concentrations of HIV-1-specific inhibitors completely suppress HIV-1 infection and prevent the emergence of drug-resistant virus. Virology 1993; 196(2): 576-585.
44. Watson KM, Buckheit CE, Buckheit RW Jr. Comparative evaluation of virus transmission inhibition by dual-acting pyrimidinedione microbicides using the microbicide transmission and sterilization assay. Antimicrob Agents Chemother 2008; 52(8): 2787-2796.
45. Cairns, G. Six Existing Drug Classes Now Being Tested as Microbicides. 2010; www.aidsmap.com/page/1438869].
46. Buckheit RJ, Lunsford R. In Vitro Performance and Analysis of Combination Anti-infective Evaluations, in Antimicrobial Drug Resistance. D.L. Mayers, Editor. 2009, Humana Press: New York. p. 1135-1149.
47. Buckheit RW Jr., Watson K, Fliakas-Boltz V, et al. SJ-3366, a unique and highly potent nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) that also inhibits HIV-2. Antimicrob Agents Chemother 2001; 45(2): 393-400.
48. Collins KB, Patterson BK, Naus GJ, et al. Development of an in vitro organ culture model to study transmission of HIV-1 in the female genital tract. Nat Med 2000; 6(4): 475-479.
49. Cummins JE Jr., Guarner J, Flowers L, et al. 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 2007; 51(5): 1770-1779.
50. Greenhead P, Hayes P, Watts PS, et al. Parameters of human immunodeficiency virus infection of human cervical tissue and inhibition by vaginal virucides. J Virol 2000; 74(12): 5577-5586.
51. Patton DL, Sweeney YT, Paul KJ. A summary of preclinical topical microbicide rectal safety and efficacy evaluations in a pigtailed macaque model. Sex Transm Dis 2009; 36(6): 350-356.
52. Denton PW, Estes JD, Sun Z, et al. Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice. PLoS Med 2008; 5(1): e16.
53. Sun Z, Denton PW, Estes JD, et al. Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1. J Exp Med 2007; 204(4): 705-714.
54. Watson-Buckheit K, Yang L, Buckheit RW Jr. Development of Dual-Acting Pyrimidinediones as Novel and Highly Potent Topical Anti-HIV Microbicides. Antimicrob Agents Chemother, 2011.