End-of-life (EOL) HIV cure-related research provides a novel approach to studying HIV reservoirs. The Last Gift is a rapid autopsy research study at the University of California San Diego that enrolls terminally ill people living with HIV (PLWHIV) with a desire to contribute to HIV cure-related research. We conducted in-depth baseline and follow-up interviews with Last Gift study participants. We analyzed interview data applying conventional content analysis. Since summer 2017, 13 participants have been enrolled (n = 11 males and 2 females; aged 45-89 years) and 8 participants interviewed. Terminal illnesses included cancers, heart diseases, and neurodegenerative illnesses. Our analysis revealed five key themes: (1) The Last Gift study has tremendous meaning for participants at the end of their life. (2) HIV-specific altruism was a primary motivator to join the Last Gift study, nested within the context of community, scientific advancement, and moral obligation. (3) Participants did not expect physical benefits yet they perceived emotional/psychological, financial, and societal/scientific benefits. (4) There were minimal participantperceived risks and concerns. (5) Last Gift participants expressed immense gratitude toward study staff. The Last Gift study provides a framework for ethical HIV cure-related research at EOL and highlighted participants' perspectives, motivations, and experiences. Knowing how PLWHIV understand and experience such studies will remain critical to designing ethical, fully informed HIV cure research protocols that are acceptable to PLWHIV.

As end-of-life (EOL) HIV cure-related research expands, understanding perspectives of participants’ next-of-kin (NOK) is critical to maintaining ethical study conduct. We conducted two small focus groups and two one-on-one interviews using focus group guides with the NOK of Last Gift study participants at the University of California, San Diego (UCSD). Participating NOK included six individuals (n = 5 male and n = 1 female), including a grandmother, grandfather, partner, spouse, and two close friends. Researchers double-coded the transcripts manually for overarching themes and sub-themes using an inductive approach. We identified six key themes: 1) NOK had an accurate, positive understanding of the Last Gift clinical study; 2) NOK felt the study was conducted ethically; 3) Perceived benefits for NOK included support navigating the dying/grieving process and personal growth; 4) Perceived drawbacks included increased sadness, emotional stress, conflicted wishes between NOK and study participants, and concerns around potential invasiveness of study procedures at the EOL; 5) NOK expressed pride in loved ones’ altruism; and 6) NOK provided suggestions to improve the Last Gift study, including better communication between staff and themselves. These findings provide a framework for ethical implementation of future EOL HIV cure-related research involving NOK.

Introduction 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. Methods We conducted a scoping review to better contextualize and understand how altruism is or could be operationalized in HIV cure-related research. We drew from the fields of altruism in general, clinical research, cancer, and HIV clinical research–including the HIV prevention, treatment, and cure-related research fields. Discussion Altruism as a key motivating factor for participation in clinical research has often been intertwined with the desire for personal benefit. The cancer field informs us that reasons for participation usually are multi-faceted and complex. The HIV prevention field offers ways to organize altruism–either by the types of benefits achieved (e.g., societal versus personal), or the origin of the values that motivate research participation. The HIV treatment literature reveals the critical role of clinical interactions in fostering altruism. There remains a dearth of in-depth knowledge regarding reasons surrounding research participation and the types of altruism displayed in HIV cure-related clinical research. Conclusion Lessons learned from various research fields can guide questions which will inform the assessment of altruism in future HIV cure-related research.

Background and objectives There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial.Design, setting, participants, & measurements Participants aged 2-20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m 2 administered twice weekly for 6 months, followed by 40 U/1.73 m 2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects. ResultsThe trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9-32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14-51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P.0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids.Conclusions ACTH at 80 U/1.73 m 2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.

In contrast to the general population, patients with chronic kidney disease (CKD) experience increased total adiponectin levels despite an increased prevalence of cardiovascular disease. Adiponectin circulates as trimer, low molecular weight (LMW), and high molecular weight (HMW) complexes. The distribution and role of each subfraction in CKD is unknown. This cross-sectional analysis examined the association of serum adiponectin and its subfractions with known cardiovascular risk factors in 105 children (median age 12 years; 56% male) enrolled into the Chronic Kidney Disease in Children (CKiD) study, an observational cohort study of children with CKD stage 2–4. HMW accounted for 46% of total adiponectin, followed by LMW (34%) and trimer (20%). In multivariable analysis, LMW was independently associated with iohexol glomerular filtration rate (GFR) (p=0.004) and was higher in pubertal versus prepubertal children (p=0.005). HMW/LMW ratio was independently associated with age and iohexol GFR (all p<0.001). Unexpectedly, systolic blood pressure was positively correlated with HMW (p=0.01), and HMW/LMW ratio (p=0.007) and inversely correlated with LMW (p=0.009). Among subfractions, only LMW was significantly correlated with left ventricular mass (LVM) index (p=0.05). In multivariable analysis, decreased LMW was independently associated with higher LVM index [β= –0.25, 95% confidence interval (CI) –0.50, –0.03, p=0.04) after adjustment for body mass index (BMI), age, and blood pressure. The higher total adiponectin levels in children with CKD are associated with higher HMW and lower LMW. This imbalance may be an important biomarker for increased cardiovascular risk despite higher levels of total adiponectin in children with CKD.