|
Harman, Sarah*
Watts, P.*, Shattock, R.*, Griffin, G.*, Van Roey, J.**
Background
TMC120 is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that demonstrates potent anti HIV-1 activity, a good resistance profile and efficacy in the vaginal hu-SCID mouse model of transmission. To evaluate the potential of this drug as active ingredient in a microbicide formulation, we have investigated TMC120 as a base compound and a formulated hydroxyethyl cellulose (HEC) gel using cellular and human cervical explant models.
Methods
Anti HIV-1 activity of TMC120 was assessed by treatment of virus, T-cell lines, or human cervical explants with either base compound or formulated gel. Results were obtained by p24 ELISA, quantitative PCR or reverse transcriptase assay. The effect of various concentrations of TMC120 on the viability of both vaginal epithelial cell lines and cervical tissue was determined using MTT assay, with Nonoxynol-9 as a control.
Results
TMC120 inhibits HIV-1 infection by X4 and R5 strains of virus in both cell based assays and cervical explant models, including migratory cells emanating from human cervical explants. Furthermore, TMC120 demonstrated significant anti-HIV memory effects, with cervical tissue resisting viral challenge up to 6 days post treatment (2 hours) with TMC120. These studies have been extended to assess the activity of TMC120 against cell-associated virus, and in the presence of semen.
Conclusions
TMC120 demonstrates good anti-viral activity in cellular and cervical explant models, and shows no toxicity at therapeutic levels, making it a good candidate microbicide.
Mrs Sarah Harman
St Georges Hosptial Medical School, Cranmer Terrace, London, SW17 0RE, United Kingdom
(Telephone) 0208 725 1432 (Fax) 0208 725 3487 (E-mail) s.harman@sghms.ac.uk
|
|
|