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Tenofovir / IQP-0528 Combination Gel Effectively Inhibits HIV and Is Not Affected by Semen
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Reported by Jules Levin
HIVR4P Oct 18-20 2016 Chicago
Cory Shetler1, Anthony Ham2, Karen Buckheit2, Robert Buckheit2, Charlene Dezzutti1,3
1Magee-Womens Research Institute, United States, 2ImQuest BioSciences, United States, 3University of Pittsburgh, United States
Background: Tenofovir (TFV), a nucleotide reverse transcriptase inhibitor, and IQP-0528, a non-nucleoside reverse transcriptase inhibitor were formulated into aqueous gels and have shown anti-HIV activity. Our premise is the combination gel would demonstrate higher potency than TFV gel or IQP-0528 gel alone and that semen would not affect the gels potency.
Methods: The combination gel contained 1% TFV and 1% IQP-0528; the single entity gels contained equivalent amounts of each drug. Using polarized ectocervical and colonic tissue explant cultures safety was defined by viability (MTT assay) and histology, while efficacy was defined by preventing HIV-1BaL infection with or without 50% whole semen over a 21 day culture period. TFV and IQP-0528 were quantified using mass spectrometry technology. Linear correlations between log10 transformed p24 levels at the end of culture (day 21) and log10 transformed drug levels were defined. To determine the 90% effective concentration (EC90), a 4-parameter Emax model was used.
Results: No change in tissue viability or epithelia was noted after 24hr exposure to the gels. The combination gel was efficacious for ectocervical and colonic tissue at 100 and 10 μM, respectively. This was similar for the IQP-0528 gel. For the TFV gel, 1000 and 100 μM, respectively was needed to prevent infection. Further testing in the presence of semen showed no impact on the potency of the TFV/IQP-0528 or TFV gel for either ectocervical or colonic tissues. Significant linear correlations for IQP-0528 (P=0.0092) and TFV-diphosphate (P=0.0184) were found in cervical tissue. EC90 values for TFV-diphosphate and IQP-0528 were 24.58 ng/mg and 3.77 ng/mg, respectively. Evaluation of colonic tissue is in progress.
Conclusions: These data show IQP-0528 is more potent than TFV and the gels were safe for ectocervical and colonic tissues. Combination gels may have advantages in areas with known circulating drug resistant virus and should be considered for future microbicide development.
NIH #U19 AI101961
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