Microbicides to prevent HIV transmission: Overcoming obstacles to chemical barrier protection

Journal of Infectious Diseases

Volumn 193, Issue 1, 2006, Pages 36-44

  Dhawan, Darpun ^a   Mayer, Kenneth H ^a,b,c,d  

^a BROWN UNIVERSITY   (United States)

^b BROWN UNIVERSITY   (United States)

^c Fenway Community Health   (United States)

^d MIRIAM HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBOPOL 974P; CARRAGEENAN; CD209 ANTIGEN; CD4 ANTIGEN; CELLULOSE SULFATE; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CCR5 ANTAGONIST; CHEMOKINE RECEPTOR CXCR4; DAPIVIRINE; GLYCOPROTEIN GP 120; GLYCOPROTEIN GP 41; KY JELLY; MICROBICIDE; N [4 CHLORO 3 (3 METHYL 2 BUTENYLOXY)PHENYL] 2 METHYL 3 FURANCARBOTHIOAMIDE; NAPHTHALENESULFONATE POLYMER; NAPHTHALENESULFONIC ACID DERIVATIVE; PRO 2000; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAVVY; TENOFOVIR; UNCLASSIFIED DRUG; VIRUS ENVELOPE PROTEIN;

ANTIVIRAL ACTIVITY; BLADDER DISEASE; BLADDER FULLNESS; CD4 LYMPHOCYTE COUNT; CHONDRUS; CLINICAL TRIAL; COLPOSCOPY; COMORBIDITY; CONDOM; CORRELATION ANALYSIS; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; DYSURIA; ERYTHEMA; HERPES SIMPLEX VIRUS; HERPES SIMPLEX VIRUS 2; HOST SUSCEPTIBILITY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFECTION PREVENTION; MEDICAL LITERATURE; MEDICAL RESEARCH; MEDLINE; PRIORITY JOURNAL; REVIEW; SEROCONVERSION; VAGINA ERYTHEMA; VAGINA SECRETION; VAGINAL PRURITUS; VIRUS ACTIVATION; VIRUS ENVELOPE; VIRUS INACTIVATION; VIRUS MUTATION; VIRUS REPLICATION; VIRUS RESISTANCE; VIRUS TRANSMISSION;

ADMINISTRATION, INTRAVAGINAL; ADMINISTRATION, TOPICAL; ANTI-HIV AGENTS; ANTI-INFECTIVE AGENTS; CLINICAL TRIALS; FEMALE; HIV INFECTIONS; HUMANS; MALE; SEXUALLY TRANSMITTED DISEASES;

EID: 29744459673     PISSN: 00221899     EISSN: None     Source Type: Journal    
DOI: 10.1086/499163     Document Type: Review

References (127)

1. United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization. AIDS epidemic update: December 2004. Geneva: UNAIDS, 2004.
2. Ojikutu BO, Stone VE. Women, inequality, and the burden of HIV. N Engl J Med 2005; 352:649-52.
3. Stein ZA. HIV prevention: the need for methods women can use. Am J Public Health 1990; 80:460-2.
4. Jennings R, Clegg A. The inhibitory effect of spermiddal agents on replication of HSV-2 and HIV-1 in-vitro. J Antimicrob Chemother 1993; 32:71-82.
5. Roddy RE, Zekeng L, Ryan KA, Tamoufe U, Weir SS, Wong EL. A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases. N Engl J Med 1998; 339:504-10.
6. Roddy RE, Cordero M, Ryan KA, Figueroa J. A randomized controlled trial comparing nonoxynol-9 lubricated condoms with silicone lubricated condoms for prophylaxis. Sex Transm Infect 1998; 74:116-9.
7. Kreiss J, Ngugi E, Holmes K, et al. Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes. JAMA 1992; 268:477-82.
8. Zekeng L, Feldblum PJ, Oliver RM, Kaptue L. Barrier contraceptive use and HIV infection among high-risk women in Cameroon. AIDS 1993; 7:725-31.
9. Van Damme L, Ramjee G, Alary M, et al. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial. Lancet 2002; 360:971-7.
10. Niruthisard S, Roddy RE, Chutivongse S. The effects of frequent nonoxynol-9 use on the vaginal and cervical mucosa. Sex Transm Dis 1991; 18:176-9.
11. Rekart ML. The toxidty and local effects of the spermicide nonoxynol 9. J Acquir Immune Defic Syndr 1992; 5:425-7.
12. 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; 184:418-28.
13. Richardson BA. Nonoxynol-9 as a vaginal microbicide for prevention of sexually transmitted infections: it's time to move on. JAMA 2002; 287:1171-2.
14. World Health Organization. WHO/CONRAD technical consultation on nonoxynol-9: report from the 9-10 October 2001 work-shop. Geneva: World Health Organization, 2001.
15. Alliance for Microbicide Development. Microbicide clinical trials. Available at: http://www.microbicide.org/publications/digest/Microbicide. Clinical.Trials.Summary.Table .October.2005.pdf. Accessed 1 November 2005.
16. Stebbing J, Gazzard B, Douek DC. Where does HIV live? N Engl J Med 2004; 350:1872-80.
17. + T cells are the earliest detectable human immunodeficiency virus type 1 (HIV-1)-infected cells in the female genital mucosal tissue during HIV-1 transmission in an organ culture system. J Virol 2002; 76:9868-76.
18. Hu J, Gardner MB, Miller CJ. Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J Virol 2000; 74:6087-95.
19. Geijtenbeek TB, Kwon DS, Torensma R, et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 2000; 100:587-97.
20. Geijtenbeek TB, van Kooyk Y. DC-SIGN: a novel HIV receptor on DCs that mediates HIV-1 transmission. Curr Top Microbiol Immunol 2003; 276:31-54.
21. Hu Q, Frank I, Williams V, et al. Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue. J Exp Med 2004; 199:1065-75.
22. Patterson BK, Landay A, Andersson J, et al. Repertoire of chemokine receptor expression in the female genital tract: implications for human immunodeficiency virus transmission. Am J Pathol 1998; 153:481-90.
23. Zaitseva M, Blauvelt A, Lee S, et al. Expression and function of CCR5 and CXCR4 on human Langerhans cells and macrophages: implications for HIV primary infection. Nat Med 1997; 3:1369-75.
24. Miller CJ, Vogel P, Alexander NJ, Dandekar S, Hendrickx AG, Marx PA. Pathology and localization of simian immunodeficiency virus in the reproductive tract of chronically infected male rhesus macaques. Lab Invest 1994; 70:255-62.
25. Miller CJ. Localization of simian immuno-deficiency virus-infected cells in the genital tract of male and female rhesus macaques. J Reprod Immunol 1998; 41:331-9.
26. Shattock R, Solomon S. Microbicides-aids to safer sex. Lancet 2004; 363:1002-3.
27. Nicolosi A, Correa Leite ML, Musicco M, Arici C, Gavazzeni G, Lazzarin A. The efficiency of male-to-female and female-to-male sexual transmission of the human immunodeficiency virus: a study of 730 stable couples. Italian Study Group on HIV Hetero-sexual Transmission. Epidemiology 1994; 5:570-5.
28. Moss GB, Clemetson D, D'Costa L, et al. Association of cervical ectopy with heterosexual transmission of human immunodeficiency virus: results of a study of couples in Nairobi, Kenya. J Infect Dis 1991; 164:588-91.
29. Mati JK, Hunter DJ, Maggwa BN, Tukei PM. Contraceptive use and the risk of HIV infection in Nairobi, Kenya. Int J Gynaecol Obstet 1995; 48:61-7.
30. Moscicki AB, Ma Y, Holland C, Vermund SH. Cervical ectopy in adolescent girls with and without human immunodeficiency virus infection. J Infect Dis 2001; 183:865-70.
31. Plourde PJ, Pepin J, Agoki E, et al. Human immunodeficiency virus type 1 seroconversion in women with genital ulcers. J Infect Dis 1994; 170:313-7.
32. Ghanem KG, Shah N, Klein RS, et al. Influence of sex hormones, HFV status, and concomitant sexually transmitted infection on cervicovaginal inflammation. J Infect Dis 2005; 191:358-66.
33. Sturm AW, Zanen HC. Characteristics of Haemophilus ducreyi in culture. J Clin Microbiol 1984; 19:672-4.
34. Croughan WS, Behbehani AM. Comparative study of inactivation of herpes simplex virus types 1 and 2 by commonly used antiseptic agents. J Clin Microbiol 1988; 26:213-5.
35. Yasin B, Pang M, Wagar EA, Lehrer RI. Examination of Chlamydia trachomatis infection in environments mimicking normal and abnormal vaginal pH. Sex Transm Dis 2002; 29:514-9.
36. Hillier SL. Diagnostic microbiology of bacterial vaginosis. Am J Obstet Gynecol 1993; 169:455-9.
37. Hill JA, Anderson DJ. Human vaginal leukocytes and the effects of vaginal fluid on lymphocyte and macrophage defense functions. Am J Obstet Gynecol 1992; 166:720-6.
38. 2-generating lactobadlli. J Infect Dis 1991; 164:94-100.
39. Martin HL, Richardson BA, Nyange PM, et al. Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis 1999; 180:1863-8.
40. Klebanoff SJ, Coombs RW Viricidal effect of Lactobacillus acidophilus on human immunodeficiency virus type 1: possible role in heterosexual transmission. J Exp Med 1991; 174:289-92.
41. Sewankambo N, Gray RH, Wawer MJ, et al. HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis. Lancet 1997; 350:546-50.
42. Taha TE, Hoover DR, Dallabetta GA, et al. Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 1998; 12:1699-706.
43. Nasio IM, Nagelkerke NJ, Mwatha A, Moses S, Ndinya-Achola JO, Plummer FA. Genital ulcer disease among STD clinic attenders in Nairobi: association with HIV-1 and circumcision status. Int J STD AIDS 1996; 7:410-4.
44. Gray RH, Wawer MJ, Brookmeyer R, et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HLV-1-discordant couples in Rakai, Uganda. Lancet 2001; 357:1149-53.
45. Fleming DT, Wasserheit IN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 1999; 75:3-17.
46. Gray RH, Li X, Wawer MJ, et al. Determinants of HLV-1 load in subjects with early and later HIV infections, in a general-population cohort of Rakai, Uganda. J Infect Dis 2004; 189:1209-15.
47. Reynolds SJ, Risbud AR, Shepherd ME, et al. Recent herpes simplex virus type 2 infection and the risk of human immunodeficiency virus type 1 acquisition in India. J Infect Dis 2003; 187:1513-21.
48. Decrion AZ, Dichamp I, Varin A, Herbein G. HIV and inflammation. Curr HIV Res 2005; 3:243-59.
49. Pilcher CD, Tien HC, Eron JJ Jr, et al. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis 2004; 189:1785-92.
50. Van Damme L. Clinical microbicide research: an overview. Trop Med Int Health 2004; 9:1290-6.
51. Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 2005; 191:1403-9.
52. Ma Z, Abel K, Rourke T, Wang Y, Miller C. A period of transient viremia and occult infection precedes persistent viremia and antiviral immune responses during multiple low-dose intravaginal simian immunodeficiency virus inoculations. J Virol 2004; 78:14048-52.
53. Cohen MS, Pilcher CD. Amplified HIV transmission and new approaches to HIV prevention. J Infect Dis 2005; 191:1391-3.
54. Wyrick PB, Knight ST, Gerbig DG Jr, et al. The microbicidal agent C31G inhibits Chlamydia trachomatis infectivity in vitro. Antimicrob Agents Chemother 1997; 41:1335-44.
55. Biosyn. C31G vaginal gel: product description. Available at: http://www.biosyn-inc.com/C31Gvag-gel.html. Accessed 1 May 2005.
56. Thompson KA, Malamud D, Storey BT. Assessment of the anti-microbial agent C31G as a spermicide: comparison with nonoxynol-9. Contraception 1996; 53:313-8.
57. Mauck CK, Weiner DH, Creinin MD, Barnhart KT, Callahan MM, Bax R. A randomized phase I vaginal safety study of three concentrations of C31G vs. Extra Strength Gynol II. Contraception 2004; 70:233-40.
58. Bax R, Douville K, McCormick D, Rosenberg M, Higgins J, Bowden M. Microbicides-evaluating multiple formulations of C31G. Contraception 2002; 66:365-8.
59. Chang TL, Chang CH, Simpson DA, et al. Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4. Proc Natl Acad Sci USA 2003; 100:11672-7.
60. Rao S, Hu S, McHugh L, et al. Toward a live microbial microbicide for HIV: commensal bacteria secreting an HIV fusion inhibitor peptide. Proc Natl Acad Sci USA 2005; 102:11993-8.
61. van De Wijgert J, Fullem A, Kelly C, et al. Phase 1 trial of the topical microbicide BufferGel: safety results from four international sites. J Acquir Immune Defic Syndr 2001; 26:21-7.
62. Mayer KH, Peipert J, Fleming T, et al. Safety and tolerability of BufferGel, a novel vaginal microbicide, in women in the United States. Clin Infect Dis 2001; 32:476-82.
63. Cosgrove-Sweeney Y, Butler K, Peterson A, Patton D. Preclinical safety evaluation of Acidform in the macaque model [abstract 02343-3]. In: Program and abstracts of Microbicides 2004 (London). London: Microbicides 2004 Event Office, 2004:62.
64. Garg S, Anderson RA, Chany CJ 2nd, et al. Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM). Contraception 2001; 64:67-75.
65. Schols D, Pauwels R, Desmyter J, De Clercq E. Dextran sulfate and other polyanionic anti-HIV compounds specifically interact with the viral gp120 glycoprotein expressed by T-cells persistently infected with HIV-1. Virology 1990; 175:556-61.
66. - cells. Science 1988; 240:646-9.
67. Indevus Pharmaceuticals. PRO 2000: product description. Available at: http://www interneuron.com/. Accessed 1 May 2005.
68. Keller MJ, Zerhouni-Layachi B, Cheshenko N, et al. PRO 2000 gel inhibits HIV and herpes simplex virus infection following vaginal application: a double-blind placebo-controlled trial. J Infect Dis 2005; 193:27-35 (in this issue).
69. Mayer KH, Karim SA, Kelly C, et al. Safety and tolerability of vaginal PRO 2000 gel in sexually active HIV-uninfected and abstinent HIV-infected women. AIDS 2003; 17:321-9.
70. Perotti ME, Pirovano A, Phillips DM. Carrageenan formulation prevents macrophage trafficking from vagina: implications for microbicide development. Biol Reprod 2003; 69:933-9.
71. Maguire RA, Bergman N, Phillips DM. Comparison of microbicides for efficacy in protecting mice against vaginal challenge with herpes simplex virus type 2, cytotoxicity, antibacterial properties, and sperm immobilization. Sex Transm Dis 2001; 28:259-65.
72. Elias CJ, Coggins C, Alvarez F, et al. Colposcopic evaluation of a vaginal gel formulation of iota-carrageenan. Contraception 1997; 56:387-9.
73. Christensen ND, Reed CA, Gulp TD, et al. Papillomavirus microbicidal activities of high-molecular-weight cellulose sulfate, dextran sulfate, and polystyrene sulfonate. Antimicrob Agents Chemother 2001; 45:3427-32.
74. Simoes JA, Citron DM, Aroutcheva A, et al. Two novel vaginal microbicides (polystyrene sulfonate and cellulose sulfate) inhibit Gardnerella vaginalis and anaerobes commonly associated with bacterial vaginosis. Antimicrob Agents Chemother 2002; 46:2692-5.
75. Polydex Pharmaceuticals. USHERCELL in depth. Available at: http://www.polydex. com/v2/research/ushercell_indepth.html. Accessed 1 May 2005.
76. Mauck C, Weiner DH, Ballagh S, et al. Single and multiple exposure tolerance study of cellulose sulfate gel: a phase I safety and colposcopy study. Contraception 2001; 64:383-91.
77. McDermott DH, Zimmerman PA, Guignard F, Kleeberger CA, Leitman SR Murphy PM. CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS). Lancet 1998; 352:866-70.
78. Alkhatib G, Combadiere C, Broder CC, et al. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 1996; 272:1955-8.
79. Lederman MM, Veazey RS, Offord R, et al. Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5. Science 2004; 306:485-7.
80. Veazey RS, Klasse PJ, Schader SM, et al. Protection of macaques from vaginal SHIV challenge by vaginally delivered inhibitors of virus-cell fusion. Nature 2005; 438:99-102.
81. Wolinsky SM, Veazey RS, Kunstman KJ, et al. Effect of a CCR5 inhibitor on viral loads in macaques dual-infected with R5 and X4 primate immunodeficiency viruses. Virology 2004; 328:19-29.
82. Wainberg M. The prospect for RT inhibitors as topical microbicides [abstract MMM-03]. In: Program and abstracts of Microbicides 2004 (London). London: Microbicides 2004 Event Office, 2004:11.
83. Mayer K, Maslankowski L, El-Sadr W, et al. Safety and tolerability of vaginal tenofovir gel (TFV) in HIV-uninfected and HIV-infected women (HPTN 050). AIDS (in press).
84. Di Fabio S, Van Roey J, Giannini G, et al. Inhibition of vaginal transmission of HIV-1 in hu-SCID mice by the non-nucleoside reverse transcriptase inhibitor TMC120 in a gel formulation. AIDS 2003; 17:1597-604.
85. Harman S, Watts P, Shattock R. TMC120 blocks HIV-1 infection in cellular and human cervical tissue models [abstract 02591]. In: Program and abstracts of Microbicides 2004 (London). London: Microbicides 2004 Event Office, 2004:76.
86. de Béthune M, Azijn H, Andries K, Janssen P, Pauwels R. In vitro selection experiments demonstrate reduced development of resistance with TMC120 and TMC125 compared with first generation NNRTI. Antiviral Ther 2001;6(Suppl 1):7.
87. Borkow G, Barnard J, Nguyen TM, Belmonte A, Wainberg MA, Parniak MA. Chemical barriers to human immunodeficiency virus type 1 (HIV-1) infection: retrovirucidal activity of UC781, a thiocarboxanilide non-nucleoside inhibitor of HIV-1 reverse transcriptase. J Virol 1997; 71:3023-30.
88. Fletcher P, Kiselyeva Y, Wallace G, et al. 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 2005; 79:11179-86.
89. Schader-Plesman S, Klasse P, Harman S, Watts P, Shattock R. PMPA-NNRTI combination studies demonstrate potent synergism against HIV-1 infection in vitro [abstract 02442]. In: Program and abstracts of Microbicides 2004 (London). London: Microbicides 2004 Event Office, 2004:68.
90. Gross M. HIV topical microbicides: steer the ship or run aground. Am J Public Health 2004; 94:1085-9.
91. Stone AB. HIV Topical microbicides: the current development strategy is fully justified. Am J Public Health 2004; 94:1845-6.
92. Mauck CK, Baker JM, Birnkrant DB, Rowe PJ, Gabelnick HL The use of colposcopy in assessing vaginal irritation in research. AIDS 2000; 14:2221-7.
93. Bollen L, Kilmarx P, Wiwatwongwana P. Photo atlas for microbicide evaluation. Bangkok: Thai Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, 2002.
94. Fichorova RN, Bajpai M, Chandra N, et al. Interleukins (IL)-1, 1L-6 and 1L-8 predict mucosal toxicity of vaginal microbicidal contraceptives. Biol Reprod 2004; 71:761-9.
95. Keller MJ, Klotman ME, Herold BC. Rigorous pre-clinical evaluation of topical microbicides to prevent transmission of human immunodeficiency virus. J Antimicrob Chemother 2003; 51:1099-102.
96. Chang TL, Vargas J Jr, DelPortillo A, Klotman ME. Dual role of α-defensin-1 in anti-HIV-1 innate immunity. J Clin Invest 2005; 115:765-73.
97. McNeely TB, Shugars DC, Rosendahl M, Tucker C, Eisenberg SP, Wahl SM. Inhibition of human immunodeficiency virus type 1 infectivity by secretory leukocyte protease inhibitor occurs prior to viral reverse transcription. Blood 1997; 90:1141-9.
98. Otten RA, Adams DR, Kim CN, et al. Multiple vaginal exposures to low doses of R5 simian-human immunodeficiency virus: strategy to study HIV preclinical interventions in nonhuman primates. J Infect Dis 2005; 191:164-73.
99. Greenhead P, Hayes P, Watts PS, Laing KG, Griffin GE, Shattock RJ. Parameters of human immunodeficiency virus infection of human cervical tissue and inhibition by vaginal virucides. J Virol 2000; 74:5577-86.
100. Miller CJ, Hu J. T cell-tropic simian immunodeficiency virus (SIV) and simian-human immunodeficiency viruses are readily transmitted by vaginal inoculation of rhesus macaques, and Langerhans' cells of the female genital tract are infected with SIV. J Infect Dis 1999; 179(Suppl 3):S413-7.
101. Woodsong C, Karim QA. A model designed to enhance informed consent: experiences from the HIV prevention trials network. Am J Public Health 2005; 95:412-9.
102. Ahmad K. Trial of antiretroviral for HIV prevention on hold. Lancet Infect Dis 2004; 4:597.
103. Fleming TR, Richardson BA. Some design issues in trials of microbicides for the prevention of HIV infection. J Infect Dis 2004; 190:666-74.
104. Stein ZA, Susser MW. Control groups in microbicide trials: in defense of orthodoxy. J Infect Dis 2005; 191:1377-8.
105. Fleming TR, Richardson BA. Reply to Skoler et al. and to Stein and Susser. J Infect Dis 2005; 191:1378-9.
106. Coplan PM, Mitchnick M, Rosenberg ZF. Public health: regulatory challenges in microbicide development. Science 2004; 304:1911-2.
107. Foss AM, Vickerman PT, Heise L, Watts CH. Shifts in condom use following microbicide introduction: should we be concerned? AIDS 2003; 17:1227-37.
108. Severy LJ, Tolley E, Woodsong C, Guest G. A framework for examining the sustained acceptability of microbicides. AIDS Behav 2005; 9:121-31.
109. Mantell JE, Myer L, Carballo-Dieguez A, et al. Microbicide acceptability research: current approaches and future directions. Soc Sci Med 2005; 60:319-30.
110. Bentley ME, Fullem AM, Tolley EE, et al. Acceptability of a microbicide among women and their partners in a 4-country phase I trial. Am J Public Health 2004; 94:1159-64.
111. Vail JG, Cohen JA, Kelly KL. Improving topical microbicide applicators for use in resource-poor settings. Am J Public Health 2004; 94:1089-92.
112. Barnhart KT, Pretorius ES, Timbers K, Shera D, Shabbout M, Malamud D. In vivo distribution of a vaginal gel: MRI evaluation of the effects of gel volume, time and simulated intercourse. Contraception 2004; 70:498-505.
113. Lard-Whiteford SL, Matecka D, O'Rear JJ, Yuen IS, Litterst C, Reichelderfer P. Recommendations for the nonclinical development of topical microbicides for prevention of HIV transmission: an update. International Working Group on Microbicides. J Acquir Immune Defic Syndr 2004; 36:541-52.
114. Chen SY, Gibson S, Weide D, McFarland W. Unprotected anal intercourse between potentially HIV-serodiscordant men who have sex with men, San Francisco. J Acquir Immune Defic Syndr 2003; 33:166-70.
115. Padian N, Marquis L, Francis DP, et al. Male-to-female transmission of human immuno-deficiency virus. JAMA 1987; 258:788-90.
116. Skurnick JH, Kennedy CA, Ferez G, et al. Behavioral and demographic risk factors for transmission of human immunodeficiency virus type 1 in heterosexual couples: report from the Heterosexual HIV Transmission Study. Clin Infect Dis 1998; 26:855-64.
117. Cock KM, Weiss HA. The global epidemiology of HIV/AIDS. Trop Med Int Health 2000; 5:A3-9.
118. Sudol KM, Phillips DM. Relative safety of sexual lubricants for rectal intercourse. Sex Transm Dis 2004; 31:346-9.
119. Phillips DM, Sudol KM, Taylor CL, Guichard L, Elsen R, Maguire RA. Lubricants containing N-9 may enhance rectal transmission of HIV and other STIs. Contraception 2004; 70:107-10.
120. Phillips DM, Taylor CL, Zacharopoulos VR, Maguire RA. Nonoxynol-9 causes rapid exfoliation of sheets of rectal epithelium. Contraception 2000; 62:149-54.
121. Patton DL, Cosgrove Sweeney YT, Rabe LK, Hillier SL. Rectal applications of nonoxynol-9 cause tissue disruption in a monkey model. Sex Transm Dis 2002; 29:581-7.
122. Tabet SR, Surawicz C, Horton S, et al. Safety and toxicity of nonoxynol-9 gel as a rectal microbicide. Sex Transm Dis 1999; 26:564-71.
123. Roehr B, Gross M, Mayer K. Creating a research and development agenda for rectal microbicides that protect against HIV infection. Report from the 7-8 June 2001 work-shop (Baltimore). New York: American Foundation for AIDS Research, 2001.
124. Abner SR, Guenthner PC, Guarner J, et al. A human colorectal expiant culture to evaluate topical microbicides for the prevention of HIV infection. J Infect Dis 2005; 192:1545-56.
125. Carballo-Dieguez A, Stein Z, Saez H, Dolezal C, Nieves-Rosa L, Diaz R Frequent use of lubricants for anal sex among men who have sex with men: the HIV prevention potential of a microbicidal gel. Am J Public Health 2000; 90:1117-21.
126. HIV Vaccines and Microbicides Resource Tracking Working Group. Tracking funding for microbicide research and development: estimates of annual investments 2000 to 2005. Geneva: Joint United Nations Programme on HIV/AIDS, 2005. Available at: http://www.unaids.org/html/pub/una-docs/ microbicidestrackingfunding_aug05_en_ pdf.pdf. Accessed 1 November 2005.
127. Harrison PF. A new model for collaboration: the alliance for microbicide development. Int J Gynaecol Obstet 1999; 67(Suppl 2):S39-53.