3rd IAS Conference on HIV Pathogenesis and Treatment
July 24 - 27, 2005, Rio de Janerio, Brazil
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Experimental NNRTI TMC 120 Appears Safe and Effective as Microbicide TMC120, a non-nucleoside reverse transcriptase inhibitor (NNRTI), has demonstrated potent anti- HIV-1 activity and efficacy in preventing vaginal transmission in a hu-SCID mouse model. In order to evaluate the potential of TMC120 as a microbicide, investigators at Tibotec studied it in human cervical explant models.In the study, anti HIV-1 activity of TMC120 (and formulations) was assessed by treatment of virus, cells, or human cervical explants with either base compound or formulated gel. Further, the activity of TMC120 in physiologically relevant fluid (semen and cervical mucus) and the effect of TMC 120 on the viability of vaginal epithelial cell lines and cervical tissue, using Nonoxynol-9 as a control, and the effects of TMC120 on cytokine expression were also evaluated. The investigators found that TMC120 inhibited HIV-1 infection in both cell based assays and cervical explant models, regardless of the viral strain (CXCR4 or CCR5). In addition, TMC120, alone and in formulation, demonstrated excellent biocompatibility with cervical tissue, induced little or no modulation of cytokine production, and physiologically relevant fluids (semen and cervical mucus) had no effect on its activity. Finally, and importantly, due to prolonged drug tissue levels, TMC-120 demonstrated significant anti-HIV memory effects, with cervical tissue resisting viral challenge up to 6 days post treatment (2 hours) with TMC120. Based on these data the authors conclude, “TMC120 demonstrates good anti-viral activity in cellular and cervical explant models, and shows no toxicity at therapeutic levels. These data suggest TMC120 represents a promising candidate microbicide.” Given the very slow development of a vaccine, these data are very encouraging since one prong of prevention efforts should, if possible, include the availability of microbicides that help prevent transmission. Although, a safe and effective microbicide has yet to be found, this study and others have given rise to hope that one becomes available in the not to distant future. 08/10/05 Reference |
