?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F31209%2F&rft.title=CCR5+antagonists+used+as+topical+microbicides+modulate+CCR5+expression+and+may+potentially+compound+HIV+infection&rft.creator=Laux%2C+Julie&rft.description=CCR5+antagonists%2C+such+as+Maraviroc+(MVC)+and+5P12-RANTES%2C+are+being+evaluated+as+HIV+preventatives.+The+advantage+of+these+drugs+is+that+they+restrict+HIV+entry+via+CCR5+receptor.+However%2C+sub-clinical+concentrations+could+paradoxically+increase+HIV+risk+by+increasing+CCR5+expression.%0D%0A%0D%0APeripheral+blood+mononuclear+cells+(PBMCs)+and+cervical+tissues+were+cultured+with+one+HIV+antiretrovirals+(ARVs)%2C+Maraviroc+(MVC)%2C+5P12-RANTES%2C+dapivirine+(DPV)%2C+or+griffithsin+(GRFT).++Immune+cells+isolated+from+PBMCs%2Fcervical+tissue+were+stained+with+live%2Fdead+stain+and+monoclonal+antibodies.+Samples+were+analyzed+using+a+BD+LSRII+flow+cytometer+and+FlowJo+v.+10.1+software.+To+determine+if+suboptimal+concentrations+of+antiretrovirals+(ARVs)+influence+HIV+susceptibility%2C+PBMCs%2Fcervical+tissue+were+treated+with+MVC%2C+5P12-RANTES%2C+DPV%2C+or+GRFT+and+challenged+with+HIV-1BaL.++Supernatant+was+collected+on+days+3%2C+7%2C+and+11+and+then+tested+for+viral+p24+by+the+AlphaLISA.+%0D%0A%0D%0AIn+PBMCs%2C+10+nM+and+1nM+MVC+induced+significant+enhancement+of+CCR5%2B+expression+levels+when+compared+to+DPV+or+GRFT+treated+cells%2C+respectively.+There+were+no+significant+changes+in+CCR5+MFI+or+percent+positive+cells+found+in+the+cervical+tissue.++HIV+replication%2C+via+p24+production%2C+did+not+increase+for+any+drug+concentration+in+PBMCs%2C+but+975nM+MVC+significantly+increased+p24+expression+in+cervical+tissue.++%0D%0A%0D%0AMVC+is+an+effective+therapeutic+for+HIV-infected+persons%2C+but+may+be+problematic+for+HIV+prevention+due+to+its+dose+and+time+dependent+qualities.+Likewise%2C+5P12-RANTES+showed+similar+trends+in+CCR5+expression.+Topical+application+of+CCR5+antagonists+may+be+effective+for+only+a+short+period+in+the+genital+tract.+Conversely%2C+DPV+and+GRFT+did+not+affect+CCR5+expression.+The+use+of+CCR5+antagonists+for+HIV+prevention+should+be+reconsidered+as+other+options+become+available.++The+public+health+impact+of+improving+topical+HIV+drugs+could+potentially+reduce+global+HIV+prevalence+and+shift+toward+an+HIV-free+world.&rft.date=2017-06-29&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F31209%2F1%2FJulie_Laux_masterthesis4_2017.pdf&rft.identifier=++Laux%2C+Julie++(2017)+CCR5+antagonists+used+as+topical+microbicides+modulate+CCR5+expression+and+may+potentially+compound+HIV+infection.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++