RESUMO
Tenofovir diphosphate (TFVdp; an active metabolite of oral HIV pre-exposure prophylaxis (PrEP)) is measured in dried blood spots (DBS) to estimate adherence. However, TFVdp's long half-life in whole blood may lead to misclassification following a recent change in adherence. PrEP's other metabolite, emtricitabine triphosphate (FTCtp), has a shorter half-life in whole blood but adherence thresholds are undefined. We characterized DBS TFVdp and FTCtp concentrations across many dosing scenarios. Population pharmacokinetic models were fit to TFVdp and FTCtp DBS concentrations from a directly observed therapy study (NCT03218592). Concentrations were simulated for 90 days of daily dosing followed by 90 days of 1 to 7 doses/week and for event-driven PrEP (edPrEP) scenarios. Thresholds of 1,000 and 200 fmol/punch, for TFVdp and FTCtp, respectively, were reflective of taking 4 doses/week (a minimum target for effective PrEP in men). TFVdp was < 1,000 fmol/punch for 17 days after initiating daily PrEP and > 1,000 fmol/punch for 62 days after decreasing to 3 doses/week. Respectively, FTCtp was < 200 fmol/punch for 4 days and > 200 fmol/punch for 6 days. Accuracy of edPrEP adherence classification depended on duration between last sex act and DBS sampling for both measures with misclassification ranging from 9-100%. These data demonstrate adherence misclassification by DBS TFVdp for 2 months following a decline in adherence, elucidating the need for FTCtp to estimate recent adherence. We provide proof of principle that individualized interpretation is needed to support edPrEP adherence monitoring. Our collective approach facilitates clinicians' ability to interpret DBS results and administer patient-centric interventions.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Masculino , Humanos , Tenofovir , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Adesão à MedicaçãoRESUMO
There are no psychological characteristics or psychopathology separating terrorists from the general population. Rather, it is group dynamics, with a particular emphasis on collective identity, that helps to explain terrorist psychology. Just as there is a diverse spectrum of kinds of terrorism, so too is there a spectrum of terrorist psychologies. Some terrorists, those in nationalist-separatist groups, such as Fatah and the IRA, are continuing with the mission of their parents who are dissident to the regime. The opposite generational provenance is seen among social-revolutionary terrorists, such as the Weather Underground and the Red Army Faction in Germany, who are rebelling against their parents' generation, which is loyal to the regime. Four waves of terrorism can be distinguished: the "anarchist wave"; the "anti-colonial wave" (nationalist-separatist), with minority groups seeking to be liberated from their colonial masters or from the majority in their country; the "new left" wave (social-revolutionary); and now the "religious" wave. With the communications revolution, a new phenomenon is emerging which may presage a fifth wave: lone wolf terrorists who through the Internet are radicalized and feel they belong to the virtual community of hatred. A typology of lone wolf terrorism is proposed.