ALDATU BIOSCIENCES INC — Department of Health and Human Services SBIR Phase II: R

Description

TheWHO guidelines recommend anti retroviral therapyARTfor all HIV infected peopleand massive efforts to expand ART access will result in andgtM adults and andgtM children on ART byat a cost of almost US$BConsequentlythe number of patients prescribed alternativeprotease inhibitorPIbased ART following failure of first line regimens will also increaseStudies of patients on PI based ART in resource limited countries have shown high rates of virologic failure atandmonths on treatmentand patients maintained on failing PI based regimens accumulate drug resistance mutationsDRMsthat hamper current and future treatment optionsResource constraints often limit the ability to collect genotype informationand genotype blind drug switching has been shown to be cost ineffective when compared to stratifying patients based on resistance genotypeThusthere is an urgent unmet need for an affordable HIV genotyping option for patients failing PIbased ARTFocused genotyping could significantly enhance patient care byoptimizing the NRTI backbone in patients failing a PI based regimen with only NRTI resistanceorpreventing ART switches in patients failing without resistance until adherence issues are rectifiedAldatu s Pan Degenerate Amplification and AdaptationPANDAAtechnology is a novel point mutation assay that enables inexpensive and high throughput focused genotypic resistance testingand such an approach could be cost saving for national ART programsPANDAA compensates for high intraand inter patient HIV genomic variability by removing secondary polymorphismsminimizing their impact on qPCR sensitivity specificityand enabling qPCR for HIV genotyping for the first timeFeasibility studies have demonstrated that PANDAAdetects NNRTI and NRTI resistant HIV variants with andgtsensitivityis HIV subtype independentandcan be multiplexed to simultaneously quantify resistance at multiple genomic positionsAldatu has pioneered the commercial development of PANDAA and established a reagent formulation that allows for the production of PANDAA based diagnostics in a thermostablesampleready formatIn this Phase II projectAldatu will apply the PANDAA technology to the development of PANDAA PIDRa rapidlow costthermostable test for detection of drug resistance in patients failing a PI based ART regimenwhich can radically improve clinical decision making in lowand middle income countriesThrough the aims proposed herewe willexperimentally validate the design of PANDAA reagents to quantify mutations associated with protease inhibitor resistance comprisingof the viral quasispeciesestablish an extensivecollaborative proficiency panel of drug resistant and drug sensitive HIVisolates for PANDAA PIDRvalidationassess PANDAA PIDRusing established performance criteria for HIV drug resistance genotyping and produce PANDAA PIDRunder GMP conditionsandverify that end usermulti site implementation of PANDAA PIDRis highly reproducibleThe first of its kinda validatedGMP produced PANDAA PIDRtest kit from Aldatu will be poised to capture a significant share of this rapidly growing diagnostic market opportunity TheWHO guidelines recommend anti retroviral therapyARTfor all HIV infected peopleand massive efforts to expand ART access will result in andgtM adults and andgtM children on ART byincluding an increased number of patients receiving protease inhibitorPIbased ART following failure of first line regimensHigh rates of virologic failure observed in patients on PI based ART in resource limited countriestogether with the high drug cost of a genotype blind approach to therapeutic decision makingnecessitate an affordable HIV genotyping option for these patients in these settingsThis SBIR project aims to develop a rapidlow costthermostable test for detection of drug resistance in patients failing a PI based ART regimenwhich can radically improve clinical decision making in lowand middle income countries