Effect of Intranodally Administered Dendritic Cell-Based HIV Vaccine in Combination With Pegylated Interferon α-2a on Viral Control Following ART Discontinuation: A Phase 2A Randomized Clinical Trial.

Introduction: Functional cure has been proposed as an alternative to lifelong antiretroviral therapy and therapeutic vaccines represent one of the most promising approaches. Materials and Methods: We conducted a double-blind randomized placebo-controlled clinical trial to evaluate the safety, immunogenicity, and effect on viral dynamics of a therapeutic vaccine produced with monocyte-derived dendritic cells (MD-DC) loaded with a high dose of heat-inactivated autologous (HIA) HIV-1 in combination with pegylated interferon alpha 2a (IFNα-2a) in people with chronic HIV-1. Results: Twenty-nine male individuals on successful ART and with CD4+ ≥450 cells/mm3 were randomized 1:1:1:1 to receive three ultrasound-guided inguinal intranodal immunizations, one every 2 weeks: (1) vaccine ~107 MD-DC pulsed with HIA-HIV-1 (1010 HIV RNA copies) (n = 8); (2) vaccine plus three doses of 180 mcg IFNα-2a at weeks 4-6 (n = 6); (3) placebo = saline (n = 7); and (4) placebo plus three doses of 180 mcg IFNα-2a (n = 8). Thereafter, treatment was interrupted (ATI). Vaccines, IFNα-2a, and the administration procedures were safe and well tolerated. All patients' viral load rebounded during the 12-week ATI period. According to groups, changes in viral set-point between pre-ART and during ATI were not significant. When comparing all groups, there was a tendency in changes in viral set-point between the vaccine group vs. vaccine + IFNα-2a group (>0.5log10p = 0.05). HIV-1-specific T-cell responses (IFN-Æ´ Elispot) were higher at baseline in placebo than in the vaccine group (2,259 ± 535 vs. 900 ± 200 SFC/106 PBMC, p = 0.028). A significant difference in the change of specific T-cell responses was only observed at week 4 between vaccine and placebo groups (694 ± 327 vs. 1,718 ± 282 SFC/106 PBMC, p = 0.04). No effect on T-cell responses or changes in viral reservoir were observed after INFα-2a administration. Discussion: Results from this study show that intranodally administered DC therapeutic vaccine in combination with IFNα-2a was safe and well-tolerated but had a minimal impact on viral dynamics in HIV-1 chronic infected participants. Clinical Trial Registration: (www.ClinicalTrials.gov), identifier NCT02767193.

Assessing Apps for Health Care Workers Using the ISYScore-Pro Scale: Development and Validation Study.

BACKGROUND: The presence of mobile phone and smart devices has allowed for the use of mobile apps to support patient care. However, there is a paucity in our knowledge regarding recommendations for mobile apps specific to health care professionals. OBJECTIVE: The aim of this study is to establish a validated instrument to assess mobile apps for health care providers and health systems. Our objective is to create and validate a tool that evaluates mobile health apps aimed at health care professionals based on a trust, utility, and interest scale. METHODS: A five-step methodology framework guided our approach. The first step consisted of building a scale to evaluate apps for health care professionals based on a literature review. This was followed with expert panel validation through a Delphi method of (rated) web-based questionnaires to empirically evaluate the inclusion and weight of the indicators identified through the literature review. Repeated iterations were followed until a consensus greater than 75% was reached. The scale was then tested using a pilot to assess reliability. Interrater agreement of the pilot was measured using a weighted Cohen kappa. RESULTS: Using a literature review, a first draft of the scale was developed. This was followed with two Delphi rounds between the local research group and an external panel of experts. After consensus was reached, the resulting ISYScore-Pro 17-item scale was tested. A total of 280 apps were originally identified for potential testing (140 iOS apps and 140 Android apps). These were categorized using International Statistical Classification of Diseases, Tenth Revision. Once duplicates were removed and they were downloaded to confirm their specificity to the target audience (ie, health care professionals), 66 remained. Of these, only 18 met the final criteria for inclusion in validating the ISYScore-Pro scale (interrator reliabilty 92.2%; kappa 0.840, 95% CI 0.834-0.847; P<.001). CONCLUSIONS: We have developed a reproducible methodology to objectively evaluate mobile health apps targeted to health care professionals and providers, the ISYScore-Pro scale. Future research will be needed to adapt the scale to other languages and across other domains (eg, legal compliance or security).

Comparison of Safety and Vector-Specific Immune Responses in Healthy and HIV-Infected Populations Vaccinated with MVA-B.

There are few studies comparing the safety and immunogenicity of the same HIV immunogen in healthy volunteers and HIV-infected individuals. We analyzed demographics, adverse events (AEs), and immunogenicity against vaccinia virus in preventive (RISVAC02, n = 24 low-risk HIV-negative volunteers) and therapeutic (RISVAC03, n = 20 successfully treated chronically HIV-1-infected individuals) vaccine phase-I clinical trials that were performed with the same design and the same immunogen (modified vaccinia virus Ankara-B: MVA-B). Total AEs were significantly higher in HIV-infected patients (mean AEs/patient 6.6 vs. 12.8 (p < 0.01)). Conversely, the number of AEs related to vaccination (AEsRV) was similar between both groups. No grade III or IV AEsRV were observed in either clinical trial. Regarding the immunogenicity, the proportion of anti-vaccinia virus antibody responders was similar in both studies. Conversely, the magnitude of response was significantly higher in HIV-infected patients (median binding antibodies at w8 267 vs. 1600 U/mL (p = 0.002) and at w18 666 vs. 3200 U/mL (p = 0.003)). There was also a trend towards higher anti-vaccinia virus neutralizing activity in HIV-infected individuals (proportion of responders 37% vs. 63% (p = 0.09); median IC50 32 vs. 64 (p = 0.054)). This study confirms the safety of MVA-B independent of HIV serostatus. HIV-infected patients showed higher immune responses against vaccinia virus.