ABSTRACT
OBJECTIVE: The aim of this study was to explore the experiences of youth living with HIV who transitioned from pediatric to adult care. METHODS: Semi-structured telephone interviews were conducted with 59 youth (mean age = 22 years) living with HIV about the transition experience, demographics, and health status. RESULTS: Of youth who transitioned to adult care, immune function (CD4) trended downward, 45% found the transition more difficult than anticipated, and 32% could not find emotional support services. Youth identified the need for increased continuity of care, assistance with logistics, improved communication with providers and caregivers, and individualized management of their transition process. CONCLUSION: Without adequate preparation, the transition process can be compromised with potentially serious health consequences. Youth living with HIV seek adult providers that can provide developmentally appropriate transition interventions that address loss, disclosure, and sexual behavior along with medical needs.
Subject(s)
Continuity of Patient Care , HIV Infections/therapy , HIV Seropositivity/therapy , Health Services Accessibility , Adolescent , Adolescent Health Services , Adult , Health Status , Humans , Interviews as Topic , Physician-Patient RelationsABSTRACT
Targeting adenovirus encoding therapeutic genes to specific cell types has become a major goal in gene therapy. Coxsackievirus and adenovirus receptor (CAR) and alpha(V) integrins have been identified as the primary cell surface components that interact with adenovirus type 5 (Ad5)-based vectors during in vitro transduction. Redirecting Ad5-based vectors requires abrogation of the natural interaction between the viral capsid and its cellular receptors and simultaneous introduction of a new binding specificity into the viral capsid. To abrogate native Ad5 tropism, fiber knob mutations Pro409Glu and Lys417Ala were each incorporated into adenoviral vectors, while the RGD motif was deleted from the penton base. In vitro transduction experiments showed that these capsid mutations eliminated Ad5 interactions with CAR and alpha(V) integrins. Moreover, incorporation in the fiber HI loop of a vitronectin-derived ligand (VN4) specific for the uPAR/CD87 receptor provided the Lys417Ala virus with an alternative entry pathway specific for uPAR-expressing cells, indicating a successful in vitro retargeting of the vector. Unexpectedly, however, simultaneous disruption of Ad5 binding to CAR and alpha(V) integrins had no effect on liver gene transfer following systemic administration in mice. This study highlights the need to understand better the molecular determinants involved in adenovirus uptake by the liver to control the fate of adenoviral vectors in vivo.
