Ian McGowan1. 1. Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. imcgowan@pitt.edu
Abstract
PURPOSE OF REVIEW: This review discusses recent developments within the field of microbicide development and considers whether there are grounds to be hopeful that it will be possible to develop a microbicide for the prevention of HIV infection. RECENT FINDINGS: Phase 2B/3 effectiveness studies of surfactant and polyanion vaginal microbicides have demonstrated modest or no effect against HIV infection and in the case of nonoxynol-9 and cellulose sulfate the potential to increase the risk of HIV acquisition. However, newer antiretroviral microbicide candidates, such as tenofovir, have shown good safety and significant efficacy in animal models and human tissue explant systems and are currently being evaluated in human effectiveness studies. New formulation platforms, such as vaginal rings, are being developed to optimize product acceptability and adherence, and far greater scrutiny of candidate microbicides is happening at both the preclinical and early clinical phase of development. SUMMARY: Drug development is an inherently high-risk activity and many promising candidates are discarded due to safety issues or lack of efficacy. Lessons learned over the last two decades have helped to improve the microbicide development pathway and provide hope that it will be possible to develop a safe and effective microbicide for HIV prevention.
PURPOSE OF REVIEW: This review discusses recent developments within the field of microbicide development and considers whether there are grounds to be hopeful that it will be possible to develop a microbicide for the prevention of HIV infection. RECENT FINDINGS: Phase 2B/3 effectiveness studies of surfactant and polyanion vaginal microbicides have demonstrated modest or no effect against HIV infection and in the case of nonoxynol-9 and cellulose sulfate the potential to increase the risk of HIV acquisition. However, newer antiretroviral microbicide candidates, such as tenofovir, have shown good safety and significant efficacy in animal models and human tissue explant systems and are currently being evaluated in human effectiveness studies. New formulation platforms, such as vaginal rings, are being developed to optimize product acceptability and adherence, and far greater scrutiny of candidate microbicides is happening at both the preclinical and early clinical phase of development. SUMMARY: Drug development is an inherently high-risk activity and many promising candidates are discarded due to safety issues or lack of efficacy. Lessons learned over the last two decades have helped to improve the microbicide development pathway and provide hope that it will be possible to develop a safe and effective microbicide for HIV prevention.
Authors: Marit Kramski; Rob J Center; Adam K Wheatley; Jonathan C Jacobson; Marina R Alexander; Grant Rawlin; Damian F J Purcell Journal: Antimicrob Agents Chemother Date: 2012-06-04 Impact factor: 5.191
Authors: Kathleen M Morrow; Joseph L Fava; Rochelle K Rosen; Sara Vargas; Julia G Shaw; E Milu Kojic; Patrick F Kiser; David R Friend; David F Katz Journal: AIDS Res Hum Retroviruses Date: 2013-12-09 Impact factor: 2.205
Authors: Kathleen M Morrow; Kristen Underhill; Jacob J van den Berg; Sara Vargas; Rochelle K Rosen; David F Katz Journal: Arch Sex Behav Date: 2014-01-23
Authors: Meropi Aravantinou; Rachel Singer; Nina Derby; Giulia Calenda; Paul Mawson; Ciby J Abraham; Radhika Menon; Samantha Seidor; Daniel Goldman; Jessica Kenney; Guillermo Villegas; Agegnehu Gettie; James Blanchard; Jeffrey D Lifson; Michael Piatak; José A Fernández-Romero; Thomas M Zydowsky; Natalia Teleshova; Melissa Robbiani Journal: AIDS Res Hum Retroviruses Date: 2012-08-27 Impact factor: 2.205
Authors: Patrick S Sullivan; Alex Carballo-Diéguez; Thomas Coates; Steven M Goodreau; Ian McGowan; Eduard J Sanders; Adrian Smith; Prabuddhagopal Goswami; Jorge Sanchez Journal: Lancet Date: 2012-07-20 Impact factor: 79.321
Authors: Claire J Forbes; Clare F McCoy; Diarmaid J Murphy; A David Woolfson; John P Moore; Abbey Evans; Robin J Shattock; R Karl Malcolm Journal: J Pharm Sci Date: 2014-03-01 Impact factor: 3.534
Authors: Nobuyuki Matoba; Adam S Husk; Brian W Barnett; Michelle M Pickel; Charles J Arntzen; David C Montefiori; Atsushi Takahashi; Kazunobu Tanno; Satoshi Omura; Huyen Cao; Jason P Mooney; Carl V Hanson; Haruo Tanaka Journal: PLoS One Date: 2010-06-15 Impact factor: 3.240
Authors: Carol S Lackman-Smith; Beth A Snyder; Katherine M Marotte; Mark C Osterling; Marie K Mankowski; Maureen Jones; Lourdes Nieves-Duran; Nicola Richardson-Harman; James E Cummins; Brigitte E Sanders-Beer Journal: AIDS Res Ther Date: 2010-07-09 Impact factor: 2.250