It was possible to relate the effect

to chromosomes 3 (27%) and 13 (20%). Hopefully, identification of the important genes may be achieved. By keeping the virus inoculum constant, this system better represents the clinical spectrum of disease. When using this system to evaluate a potential vaccine, it was found that mice, under the age of one year, could be protected. However, there was a range of effectiveness, from good protection to inactive. These variations may give a representation of human diversity. Angela Kashuba, University of North Carolina at Chapel Hill, NC, USA In four clinical studies, Protease Inhibitor Library cell assay Truvada [a combination pill containing TDF and emtricitabine (FTC)] was taken once daily to prevent HIV transmission, known as pre-exposure prophylaxis (PrEP). The adherence rates were unexpectedly poor in all four studies, particularly low in the study including at risk women. For example in one study, “high adherence” was defined as subjects taking at least 80% of drug doses and was achieved by only 54% of subjects. Possible reasons may have been the apparent risk of side-effects (the long consent form included 7 pages of side-effects) and the perception that the subjects, as individuals, were not

particularly at risk of infection by HIV. Importantly, the trial did confirm the concept that PrEP could be effective. There was >90% protection in those subjects generally taking 7 doses/week and there was some protection, albeit much less, in subjects taking 2 doses/week. Adherence rates, reported by subjects, were appreciably higher AZD6244 in vivo than the rates evidenced by drug blood level measurements taken just before the next dose (i.e. 24 h after previous dose). In an attempt to better understand and model these data, the drug concentrations (TDF/TFV and FTC) in various tissues were measured. The ratio between drug concentrations in blood and tissue samples differed greatly for TDF/TFV, with less variations for FTC. Concentration ratios of TDF/TFV were about 50 in rectal tissue but only 0.2 in vaginal tissue. For FTC, the ratios were 2.6 and 1.3, respectively. When considering

the possible consequences of Nintedanib (BIBF 1120) missed doses, the time scale for HIV infection is an important factor. It is thought that HIV takes about 1–3 h to reach the epithelial cells. Clearly, adherence is a critical factor for efficacy and so a real-time objective method for measuring adherence is urgently needed before further clinical studies are initiated. Travis K. Warren, USAMRIID, Fort Detrick, MD, USA Ebola and Marburg viruses are members of the filovirus family. Even in recent outbreaks of these diseases, including the current Ebola epidemic in West Africa, care workers are becoming infected and dying. Drugs, which are being investigated for treating these diseases, are progressed under the FDA “Animal Rule”. BCX4430 is a C-nucleoside adenine analog (Fig. 10) which is being progressed by BioCryst Pharmaceuticals Inc.