The question of what motivates people to participate in research is particularly salient in the HIV field. While participation in HIV research was driven by survival in the 1980's and early 1990's, access to novel therapies became the primary motivator with the advent of combination antiretroviral therapy (cART) in the late 1990s. In the HIV cure-related research context, the concept of altruism has remained insufficiently studied.
Abstract Objectives Temporal lobe epilepsy ( TLE ) is known to affect large‐scale gray and white matter networks, and these network changes likely contribute to the verbal memory impairments observed in many patients. In this study, we investigate multimodal imaging patterns of brain alterations in TLE and evaluate the sensitivity of different imaging measures to verbal memory impairment. Methods Diffusion tensor imaging ( DTI ), volumetric magnetic resonance imaging ( vMRI ), and resting‐state functional MRI (rs‐ fMRI ) were evaluated in 46 patients with TLE and 33 healthy controls to measure patterns of microstructural, structural, and functional alterations, respectively. These measurements were obtained within the white matter directly beneath neocortex (ie, superficial white matter [ SWM] ) for DTI and across neocortex for vMRI and rs‐ fMRI . The degree to which imaging alterations within left medial temporal lobe/posterior cingulate ( LMT / PC ) and left lateral temporal regions were associated with verbal memory performance was evaluated. Results Patients with left TLE and right TLE both demonstrated pronounced microstructural alterations (ie, decreased fractional anisotropy [ FA ] and increased mean diffusivity [ MD ]) spanning the entire frontal and temporolimbic SWM , which were highly lateralized to the ipsilateral hemisphere. Conversely, reductions in cortical thickness in vMRI and alterations in the magnitude of the rs‐ fMRI response were less pronounced and less lateralized than the microstructural changes. Both stepwise regression and mediation analyses further revealed that FA and MD within SWM in LMT / PC regions were the most robust predictors of verbal memory, and that these associations were independent of left hippocampal volume. Significance These findings suggest that microstructural loss within the SWM is pronounced in patients with TLE , and injury to the SWM within the LMT / PC region plays a critical role in verbal memory impairment.
The U.S. National Institute of Allergies and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH) have a new research priority: inclusion of terminally ill persons living with HIV (PLWHIV) in HIV cure-related research. For example, the Last Gift is a clinical research study at the University of California San Diego (UCSD) for PLWHIV who have a terminal illness, with a prognosis of less than 6 months. As end-of-life (EOL) HIV cure research is relatively new, the scientific community has a timely opportunity to examine the related ethical challenges. Following an extensive review of the EOL and HIV cure research ethics literature, combined with deliberation from various stakeholders (biomedical researchers, PLWHIV, bioethicists, and socio-behavioral scientists) and our experience with the Last Gift study to date, we outline considerations to ensure that such research with terminally ill PLWHIV remains ethical, focusing on five topics: 1) protecting autonomy through informed consent, 2) avoiding exploitation and fostering altruism, 3) maintaining a favorable benefits/risks balance, 4) safeguarding against vulnerability through patient-participant centeredness, and 5) ensuring the acceptance of next-of-kin/loved ones and community stakeholders. EOL HIV cure-related research can be performed ethically and effectively by anticipating key issues that may arise. While not unique to the fields of EOL or HIV cure-related research, the considerations highlighted can help us support a new research approach. We must honor the lives of PLWHIV whose involvement in research can provide the knowledge needed to achieve the dream of making HIV infection curable.
