The use of suboptimal antiretroviral therapy when applying for migration to Australia: a case series.

Background Australia imposes restrictions for people living with HIV (PLHIV) applying for permanent residency (PR), including spending less than AUD51,000 on medical costs over 10years. Some PLHIV opted for suboptimal and cheaper antiretroviral therapy (ART) regimens to increase their chances of receiving PR. We collated a case series to examine PLHIV on suboptimal ART because of visa issues. Methods We identified all patients applying for a PR in Australia who obtained nevirapine, efavirenz or zidovudine between July 2022 and July 2023 from the Melbourne Sexual Health Centre. Pathology results and records detailing psychological issues relating to the patients' wishes to remain on suboptimal ART were extracted from clinical records by two researchers. Results We identified six patients with a mean age of 39years migrating from Asian and European countries. Three patients used efavirenz, and three used nevirapine. All desired to remain on cheaper, suboptimal ART to stay below visa cost thresholds, which they considered to aid favourably with their application. Four displayed stress and anxiety arising from visa rejections, appeal deadlines and the lengthy visa application process. Conclusions Despite access to more effective and safer ART, we identified patients who chose to remain on cheaper ART to improve chances of obtaining an Australian visa, potentially putting their health at risk. We found significant evidence of stress and anxiety among patients. There is a need to review and revise current migration policies and laws in Australia that discriminate against PLHIV and jeopardise public health.

Effect of high dose vitamin D3 on the HIV-1 reservoir: A pilot randomised controlled trial.

Introduction: Antiretroviral therapy for people living with HIV-1 must be taken lifelong due to the persistence of latent virus in long-lived and proliferating CD4+ T cells. Vitamin D3 is a steroidal gene transcription regulator which exerts diverse effects on immune and epithelial cells including reductions in CD4+ T cell proliferation and improvement in gut barrier integrity. We hypothesised that a high dose of vitamin D3 would reduce the size of the HIV-1 reservoir by reducing CD4+ T cell proliferation. Methods: We performed a randomised placebo-controlled trial evaluating the effect of 24 weeks of vitamin D3 (10,000 international units per day) on the HIV-1 reservoir and immunologic parameters in 30 adults on antiretroviral therapy; participants were followed for 12 weeks post-treatment. The primary endpoint was the effect on total HIV-1 DNA at week 24. Parameters were assessed using mixed-effects models. Results: We found no effect of vitamin D3 on the change in total HIV-1 DNA from week 0 to week 24 relative to placebo. There were also no changes in integrated HIV-1 DNA, 2-long-terminal repeat (2-LTR) circles or cell-associated HIV-1 RNA. Vitamin D3 induced a significant increase in the proportion of central memory CD4+ and CD8+ T cells, a reduction in the proportion of senescent CD8+ T cells and a reduction in the natural killer cell frequency at all time points including week 36, 12 weeks after the study drug cessation. At week 36, there was a significant reduction in total HIV-1 DNA relative to placebo and persistently elevated 25-hydroxyvitamin D levels. No significant safety issues were identified. Conclusions: Vitamin D3 administration had a significant impact on the T cell differentiation but overall effects on the HIV-1 reservoir were limited and a reduction in HIV-1 DNA was only seen following cessation of the study drug. Additional studies are required to determine whether the dose and duration of vitamin D3 can be optimised to promote a continued depletion of the HIV-1 reservoir over time. Trial registration: ClinicalTrials.gov NCT03426592.

Systematic evaluation of three porcine-derived collagen membranes for guided bone regeneration.

Guided bone regeneration is one of the most common surgical treatment modalities performed when an additional alveolar bone is required to stabilize dental implants in partially and fully edentulous patients. The addition of a barrier membrane prevents non-osteogenic tissue invasion into the bone cavity, which is key to the success of guided bone regeneration. Barrier membranes can be broadly classified as non-resorbable or resorbable. In contrast to non-resorbable membranes, resorbable barrier membranes do not require a second surgical procedure for membrane removal. Commercially available resorbable barrier membranes are either synthetically manufactured or derived from xenogeneic collagen. Although collagen barrier membranes have become increasingly popular amongst clinicians, largely due to their superior handling qualities compared to other commercially available barrier membranes, there have been no studies to date that have compared commercially available porcine-derived collagen membranes with respect to surface topography, collagen fibril structure, physical barrier property, and immunogenic composition. This study evaluated three commercially available non-crosslinked porcine-derived collagen membranes (Striate+TM, Bio-Gide® and CreosTM Xenoprotect). Scanning electron microscopy revealed similar collagen fibril distribution on both the rough and smooth sides of the membranes as well as the similar diameters of collagen fibrils. However, D-periodicity of the fibrillar collagen is significantly different among the membranes, with Striate+TM membrane having the closest D-periodicity to native collagen I. This suggests that there is less deformation of collagen during manufacturing process. All collagen membranes showed superior barrier property evidenced by blocking 0.2-16.4 µm beads passing through the membranes. To examine the immunogenic agents in these membranes, we examined the membranes for the presence of DNA and alpha-gal by immunohistochemistry. No alpha-gal or DNA was detected in any membranes. However, using a more sensitive detection method (real-time polymerase chain reaction), a relatively strong DNA signal was detected in Bio-Gide® membrane, but not Striate+TM and CreosTM Xenoprotect membranes. Our study concluded that these membranes are similar but not identical, probably due to the different ages and sources of porcine tissues, as well as different manufacturing processes. We recommend further studies to understand the clinical implications of these findings.

Accuracy of mandibular repositioning surgery using new technology: Computer-aided design and manufacturing customized surgical cutting guides and fixation plates.

INTRODUCTION: Recent 3-dimensional technology advancements have resulted in new techniques to improve the accuracy of intraoperative transfer. This study aimed to validate the accuracy of computer-aided design and manufacturing (CAD-CAM) customized surgical cutting guides and fixation plates on mandibular repositioning surgery performed in isolation or combined with simultaneous maxillary repositioning surgery. METHODS: Sixty patients who underwent mandibular advancement surgery by the same surgeon were retrospectively evaluated by 3-dimensional surface-based superimposition. A 3-point coordinate system (x, y, z) was used to identify the linear and angular discrepancies between the planned movements and actual outcomes. Wilcoxon rank sum test was used to compare the outcomes between the mandible-only and the bimaxillary surgery groups with significance at P <0.05. Pearson correlation coefficient compared planned mandible advancement to the outcome from advancement planned. The centroid, which represents the mandible as a single unit, was computed from 3 landmarks, and the discrepancies were evaluated by the root mean square error (RMSE) for clinical significance set at 2 mm for linear discrepancies and 4° for angular discrepancies. RESULTS: There was no statistically significant difference between the planned and actual position of the mandible in either group when considering absolute values of the differences. When considering raw directional data, a statistically significant difference was identified in the y-axis suggesting a tendency for under-advancement of the mandible in the bimaxillary group. The largest translational RMSE for the centroid was 0.77 mm in the sagittal dimension for the bimaxillary surgery group. The largest rotational RMSE for the centroid was 1.25° in the transverse dimension for the bimaxillary surgery group. Our results show that the precision and clinical feasibility of CAD-CAM customized surgical cutting guides and fixation plates on mandibular repositioning surgery is well within clinically acceptable parameters. CONCLUSION: Mandibular repositioning surgery can be performed predictably and accurately with the aid of CAD-CAM customized surgical cutting guides and fixation plates with or without maxillary surgery.

The Influence of Anticipated HIV Stigma on Health-related Behaviors, Self-rated Health, and Treatment Preferences Among People Living with HIV in East Asia.

Long-acting injectable regimens for HIV treatment have been developed which are less frequent, more discreet, and more desirable for some people living with HIV (PLHIV) and may help reduce stigma-related barriers to HIV treatment. However, there is little information on the relationship between reported stigma and preference for these newer treatments. We characterized anticipated, experienced, and internalized HIV stigma and examined the associations with treatment preferences among an international sample of PLHIV. Data came from the international, web-based, cross-sectional study called "Positive Perspectives" conducted among PLHIV aged ≥ 18 years in 25 geographic locations during 2019 (n = 2389). Descriptive analyses were stratified among East Asian (n = 230) vs. non-Asian (n = 2159) participants. Results showed that prevalence of anticipated stigma was significantly higher among East Asian than non-Asian participants (72.2%[166/230] vs. 63.8%[1377/2159], p = 0.011). A significantly higher percentage of East Asian (68.7%[158/230]) than non-Asian participants (43.3%[935/2159] indicated that someone finding their HIV pills would cause them much "stress or anxiety" (p < 0.001). Actions taken by some PLHIV to prevent unwanted disclosure included restricting who they shared their HIV status with, hiding their HIV pills, or even skipping a dose altogether because of privacy concerns. Overall, 50.0%[115/230] East Asian participants believed HIV would reduce their lifespan and 43.0%[99/230] no longer planned for their old age because of HIV. Anticipated stigma was strongly associated with receptivity to non-daily regimens. Concerted efforts to reduce stigma and deliver flexible treatment options that address the unmet treatment needs of PLHIV, including confidentiality concerns, may improve their health-related quality of life.

Tackling structural stigma: a systems perspective.

INTRODUCTION: Structural stigma in the global HIV response is a "moving target" that constantly evolves as the epidemic changes. Tackling structural stigma requires an understanding of the drivers and facilitators of stigma in complex community, policy and health systems. In this paper, we present findings from a study adopting a systems perspective to understand how to tackle structural stigma via the Meaningful Involvement of People with HIV/AIDS (MIPA), while highlighting the challenges in demonstrating peer leadership from people living with HIV (PLHIV). METHODS: Through a long-term ongoing community-research collaboration (2015-2023), the study applied systems thinking methods to draw together the insights of over 90 peer staff from 10 Australian community and peer organizations. We used hypothetical narratives, affinity methods and causal loop diagrams to co-create system maps that visualize the factors that influence the extent to which peer leadership is expected, respected, sought-out and funded in the Australian context. We then developed draft indicators of what we should see happening when PLHIV peer leadership and MIPA is enabled to challenge structural stigma. RESULTS: Participants in the collaboration identified the interactions at a system level, which can enable or constrain the quality and influence of PLHIV peer leadership. Participants identified that effective peer leadership is itself affected by structural stigma, and peer leaders and the programmes that support and enable peer leadership must navigate a complex network of causal pathways and strategic pitfalls. Participants identified that indicators for effective PLHIV peer leadership in terms of engagement, alignment, adaptation and influence also required indicators for policy and service organizations to recognize their own system role to value and enable PLHIV peer leadership. Failing to strengthen and incorporate PLHIV leadership within broader systems of policy making and health service provision was identified as an example of structural stigma. CONCLUSIONS: Incorporating PLHIV leadership creates a virtuous cycle, because, as PLHIV voices are heard and trusted, the case for their inclusion only gets stronger. This paper argues that a systems perspective can help to guide the most productive leverage points for intervention to tackle structural stigma and promote effective PLHIV leadership.

Clinical Immunogenicity Evaluation of Eptinezumab, a Therapeutic Humanized Monoclonal Antibody Targeting Calcitonin Gene-Related Peptide (CGRP) for the Preventive Treatment of Migraine.

Background: Eptinezumab is a humanized monoclonal antibody that selectively binds calcitonin gene-related peptide and is indicated for the preventive treatment of migraine in adults. This analysis characterizes the immunogenic profile of eptinezumab using data from clinical trials of eptinezumab for migraine prevention. Methods: Immunogenicity data were collected from five studies that included 2076 patients with episodic or chronic migraine treated with eptinezumab at dose levels ranging from 10 to 1000 mg, administered intravenously for up to 4 doses at 12-week intervals. Anti-drug antibody (ADA) results were available from 2074 of these patients. Four studies were randomized, double-blind, placebo-controlled trials with ADA monitoring for up to 56 weeks; one was a 2-year, open-label, phase 3 safety study with ADA monitoring for 104 weeks. Patients who had a confirmed ADA-positive result at the end-of-study visit were monitored for up to 6 additional months. Development of ADA and neutralizing antibodies (NAbs) were evaluated to explore three key areas of potential impact: pharmacokinetic exposure profile (eptinezumab trough plasma concentrations), efficacy (change in monthly migraine days), and safety (rates of treatment-emergent adverse events). These studies included methods designed to capture the dynamics of a potential humoral immune response to eptinezumab treatment, and descriptive analyses were applied to interpret the relationship of ADA signals to drug exposure, efficacy, and safety. Results: Pooled across the five clinical trials, treatment-emergent ADAs and NAbs occurred in 15.8 and 6.2% of eptinezumab-treated patients, respectively. Highly consistent profiles were observed across all studies, with initial onset of detectable ADA observed at the week 8 measurement and maximal ADA frequency and titer observed at week 24, regardless of eptinezumab dose level or number of doses. After 24 weeks, the ADA and NAb titers steadily declined despite additional doses of eptinezumab. Interpretation: Collectively, these integrated analyses did not demonstrate any clinically meaningful impact from ADA occurring after treatment with eptinezumab. The ADA profiles were low titer and transient, with the incidence and magnitude of ADA or NAb responses declining after week 24. Development of ADAs and NAbs did not impact the efficacy and safety profiles of eptinezumab.

Client-led care in HIV: perspectives from community and practice.

OBJECTIVES: While current antiretroviral and care strategies can effectively suppress HIV, achieving optimal quality of life (QoL) requires a wider consideration of clients' well-being, the complexity of individuals' lives and social determinants of health. The objective of this commentary was to develop a definition of client-led care in the Australian context and its key supporting principles for people living with HIV (PLHIV). METHODS: The authors used two sources of evidence to support their HIV community experience with client-led care: (1) a scoping review of the literature, and (2) consultations with colleagues who were PLHIV advocates or HIV specialist physicians. The findings from the scoping review and consultations were summarised and the key principles of client-led care compared with those identified by the authors. RESULTS: Seven articles met the inclusion criteria for qualitative analysis in the scoping review. Five PLHIV advocates and three HIV specialist physicians were consulted. Key principles supporting client-led care identified by the authors based on their experience centred around the themes of: (1) clients and healthcare providers working in partnership, (2) information and communication, (3) coordinating access to care, (4) building trust, and (5) respect for client's needs and preferences. The principles identified by the authors were supported by those of the scoping review and colleague consultations. CONCLUSIONS: A client-led approach can complement conventional HIV care strategies and enable empowerment and greater engagement with care, potentially improving the care continuum and overall QoL for individuals living with HIV who can, and want to, lead their own care.

Long-term safety and tolerability of eptinezumab in patients with chronic migraine: a 2-year, open-label, phase 3 trial.

BACKGROUND: Eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody recently approved in the United States for preventive treatment of migraine in adults, was found to be well tolerated in double-blind, placebo-controlled studies in patients with episodic and chronic migraine. The objective of the PREVAIL study was to evaluate the long-term safety, immunogenicity, and impact on patient-reported outcomes of repeat doses of eptinezumab in patients with chronic migraine. METHODS: PREVAIL was an open-label, phase 3 trial comprising a 48-week treatment phase followed by a second 48-week treatment phase. Adults with chronic migraine received eptinezumab 300 mg by 30-min intravenous administration every 12 weeks for up to 8 doses. Patients were followed for 20 weeks after the final infusion (end-of-study visit at week 104). RESULTS: Overall, 128 adults (mean age, 41.5 years) with chronic migraine were included. During the 2 years, the most frequently reported treatment-emergent adverse events were nasopharyngitis (14.1%), upper respiratory tract infection (7.8%), sinusitis (7.8%), influenza (6.3%), bronchitis (5.5%), and migraine (5.5%). The rate of study-drug discontinuation due to adverse events was 6.3%, which included 3 patients with infusion-related hypersensitivity. The incidence of anti-eptinezumab antibodies peaked at week 24 and declined despite continued dosing, to nondetectable levels at week 104. Improvements in patient-reported outcomes were observed at first assessment (week 4) and generally sustained through week 104. CONCLUSION: In adults with chronic migraine, eptinezumab 300 mg demonstrated a favorable safety profile, limited long-term immunogenicity, early and sustained reductions in migraine-related burden, and improvements in health-related quality of life over 2 years. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02985398 ).

Regional differences in perceived treatments needs and priorities in relation to antiretroviral therapy among people living with HIV in 25 countries.

While geographic differences in HIV burden are well documented, less is known about regional differences in perceived treatment needs. To fill this gap, the 2019 Positive Perspectives study of people living with HIV (PLHIV) was conducted in 25 countries across Northern America, Latin America, the Asian region, Europe (EU/Schengen countries), Russia, Australia, and South Africa (n = 2389). Overall mean duration of HIV was 10.1 (SD = 9.6) years. The perception that HIV had a negative impact on day-to-day life was lowest among participants from South Africa (14.0%[25/179]) and highest among participants from the Asian region (55.2%[127/230]). Most of the regional gap in the perception that HIV had a negative impact on daily life was explained by regional differences in medication-related unmet needs, stigma, demographic factors, and comorbidities. The percentage who felt they understood their treatment was highest among participants from Australia (87.5%[105/120]) and lowest among those from Russia (62.0%[93/150]), the Asian region (62.2%[143/230]), and South Africa (62.6%[112/179]). Among participants from Northern America, Europe, and Latin America, the treatment goals with the largest absolute increase in perceived importance, from time of starting treatment to time of survey among those diagnosed for ≥1 year, were minimizing the long term impact of antiretroviral treatment and keeping the number of medicines in their antiretroviral regimen at a minimum. Tailored approaches to care of PLHIV are needed as different regions have different disease burden and treatment needs. Equitable approaches to HIV care are needed across and within regions to ensure that patients' unmet needs and preferences are addressed to improve their overall wellbeing and health-related quality of life.

Shared Decision Making Between Patients and Healthcare Providers and its Association with Favorable Health Outcomes Among People Living with HIV.

We assessed patient-provider communication in HIV care; data were from the 2019 Positive Perspectives Survey of people living with HIV (PLHIV) from 25 countries (n = 2389). A significantly greater proportion of recently diagnosed individuals were interested in being involved when it comes to decisions about their HIV treatment compared with any other group (72.8% [399/548], 63.1% [576/913], and 62.6% [581/928], diagnosis year: 2017-2019, 2010-2016, and pre-2010 respectively) but reported less understanding of their treatment compared with those reporting the longest duration (66.8% [366/548], 68.6% [626/913], and 77.3% [717/928], respectively). One-third of PLHIV with salient treatment-related concerns were uncomfortable discussing with providers. Of participants who felt that their HIV medication limited their life but did not discuss their concerns with their provider (n = 203), top reasons for not discussing were: perception nothing could be done (49.3% [100/203]), provider never brought up the issue (37.9% [77/203]), and not wanting to appear difficult (30.5% [62/203]). To continue to identify and address unmet treatment needs among PLHIV, providers need to ensure that there is ongoing open dialogue.

Physical, Emotional, and Psychosocial Challenges Associated with Daily Dosing of HIV Medications and Their Impact on Indicators of Quality of Life: Findings from the Positive Perspectives Study.

To assess challenges with daily oral antiretroviral therapy (ART), we analyzed data for 2389 participants in the 2019 Positive Perspectives survey of people living with HIV in 25 countries. ART-related challenges reported included difficulty swallowing pills (33.1% [790/2389]); stress from daily dosing routine (33.3% [795/2389]); bad memories from daily intake of HIV medication (35.1%[839/2389]), and concern "that having to take pills every day means a greater chance of revealing my HIV status to others" (37.9% [906/2389]). Individuals who felt empowered by daily oral dosing ["taking my pill(s) every day reassures me that my HIV is being kept under control"] had 69% higher odds of optimal overall health (AOR 1.69, 95% CI 1.40-2.04). Conversely, odds of optimal overall health were lower among those who felt daily pill intake "limits my day-to-day life" (AOR 0.53, 95% CI 0.44-0.64). These findings show that there is need for increased flexibility of ART delivery to meet diverse patient needs.

Collagen Membrane for Guided Bone Regeneration in Dental and Orthopedic Applications.

Treatment of cortical bone defects is a clinical challenge. Guided bone regeneration (GBR), commonly used in oral and maxillofacial dental surgery, may show promise for orthopedic applications in repair of cortical bone defects. However, a limitation in the use of GBR for cortical bone defects is the lack of an ideal scaffold that provides sufficient mechanical support to bridge the cortical bone with minimal interference in the repair process. We have developed a new collagen membrane, CelGro™, for use in GBR. We report the material characterization of CelGro and evaluate the performance of CelGro in translational preclinical and clinical studies. The results show CelGro has a bilayer structure of different fiber alignment and is composed almost exclusively of type I collagen. CelGro was found to be completely acellular and free from xenoantigen, α-gal (galactose-alpha-1,3-galactose). In the preclinical study of a rabbit cortical bone defect model, CelGro demonstrated enhanced bone-remodeling activity and cortical bone healing. Microcomputed tomography evaluation showed early bony bridging over the defect area 30 days postoperatively, and nearly complete restoration of mature cortical bone at the bone defect site 60 days postoperatively. Histological analysis 60 days after surgery further confirmed that CelGro enables bridging of the cortical bone defect by induction of newly formed cortical bone. Compared to a commercially available collagen membrane, Bio-Gide®, CelGro showed much better cortical alignment and reduced porosity at the defect interface. As selection of orthopedic patients with cortical bone defects is complex, we conducted a clinical study evaluating the performance of CelGro in guided bone regeneration around dental implants. CelGro was used in GBR procedures in a total of 16 implants placed in 10 participants. Cone-beam computed tomography images show significantly increased bone formation both horizontally and vertically, which provides sufficient support to stabilize implants within 4 months. Together, the findings of our study demonstrate that CelGro is an ideal membrane for GBR not only in oral and maxillofacial reconstructive surgery but also in orthopedic applications (Clinical Trial ID ACTRN12615000027516).

Undetectable equals untransmittable (U = U): awareness and associations with health outcomes among people living with HIV in 25 countries.

OBJECTIVES: 'Undetectable equals Untransmittable' (U=U) is an empowering message that may enable people living with HIV (PLHIV) to reach and maintain undetectability. We estimated the percentage of PLHIV who ever discussed U=U with their main HIV care provider, and measured associations with health-related outcomes. Secondarily, we evaluated whether the impact of the U=U message varied between those who heard it from their healthcare provider (HCP) vs from elsewhere. METHODS: Data were from the 25-country 2019 Positive Perspectives Survey of PLHIV on treatment (n=2389). PLHIV were classified as having discussed U=U with their HCP if they indicated that their HCP had ever told them about U=U. Those who had not discussed U=U with their HCP but were nonetheless aware that 'My HIV medication prevents me from passing on HIV to others' were classified as being made aware of U=U from non-HCP sources. Multivariable logistic regression was used to measure associations between exposure to U=U messages and health outcomes. RESULTS: Overall, 66.5% reported ever discussing U=U with their HCP, from 38.0% (South Korea) to 87.3% (Switzerland). Prevalence was lowest among heterosexual men (57.6%) and PLHIV in Asia (51.3%). Compared with those unaware of U=U, those reporting U=U discussions with their HCP had lower odds of suboptimal adherence (AOR=0.59, 95% CI 0.44 to 0.78) and higher odds of self-reported viral suppression (AOR=2.34, 95% CI 1.72 to 3.20), optimal sexual health (AOR=1.48, 95% CI 1.14 to 1.92) and reporting they 'always shared' their HIV status (AOR=2.99, 95% CI 1.42 to 6.28). While exposure to U=U information from non-HCP sources was beneficial too, the observed associations were attenuated relative to those seen with reported discussions with HCPs. CONCLUSION: HCP discussion of U=U with PLHIV was associated with favourable health outcomes. However, missed opportunities exist since a third of PLHIV reported not having any U=U discussion with their HCP. U=U discussions with PLHIV should be considered as a standard of care in clinical guidelines.

Time for revolution? Enhancing meaningful involvement of people living with HIV and affected communities in HIV cure-focused science.

INTRODUCTION: Involving affected communities and people living with HIV (PLHIV) in HIV cure-focused clinical trials has ethical and practical benefits. However, there can be barriers to meaningful involvement of 'lay people' in scientific research meaning community consultation is often limited or tokenistic. This paper reports on an Australian project, the INSPIRE project (Improve, Nurture and Strengthen education, collaboration, and communication between PLHIV and Researchers), which aimed to explore barriers and enablers to enactment of the principles of meaningful involvement of PLHIV (MIPA) and affected communities in HIV cure-focused research. METHODS: The project involved a workshop attended by 40 stakeholders involved in HIV care, research or advocacy including PLHIV, community organizations, basic scientists, and clinicians. The workshop involved a facilitated discussion about community involvement in a hypothetical HIV cure-focused clinical trial. Data were collected through notetaking and video recordings. Qualitative, thematic analysis was undertaken to organize the data and identify core themes related to MIPA. RESULTS: Workshop discussions revealed community stakeholders often feel their involvement in HIV clinical research is undervalued, evidenced by limited financial remuneration and minimal capacity to influence the research design or processes. Building long-term, formal and informal relationships between community organizations, PLHIV, researchers and research teams or laboratories was identified as a strategy to support MIPA at all stages of a clinical trial, from design to dissemination of findings. CONCLUSIONS: Enacting MIPA principles in HIV cure-focused research requires a better understanding of the potential to improve research outcomes and ensure quality in the research process.

Acceptability, motivation and the prospect of cure for people living with HIV and their healthcare providers in HIV cure-focused treatment interruption studies.

BACKGROUND: Analytical treatment interruptions (ATI) are commonly used clinical endpoints to assess interventions aimed at curing HIV or achieving antiretroviral therapy (ART)-free HIV remission. Understanding the acceptability of ATI amongst people living with HIV (PLHIV) and their HIV healthcare providers (HHP) is limited. METHODS: Two online surveys for PLHIV and HHP assessed awareness and acceptability of ATI, and understanding of the prospect for HIV cure in the future. Responses were collected from July 2017-January 2018. A descriptive analysis was performed and similar questions across the two surveys were compared using χ squared test. RESULTS: 442 PLHIV and 144 HHP completed the survey. 105/400 (26%) PLHIV had ever interrupted ART, 8% of which were in a clinical trial. Altruistic motivations were drivers of participation of PLHIV in cure related research. 81/135 (60%) HHP would support their patients wishing to enrol in an HIV cure-focused trial, but fewer would promote and allow such participation (25% and 31% respectively). Compared to HHP, PLHIV were more likely to believe that an HIV cure would be achievable within 10 years (55% vs. 19%, p < 0.001), had less awareness of ATI (46% vs. 62%, p < 0.001) and were less likely to have had experience of either participation or enrolment in an ATI study (5% vs. 18%, p < 0.001) CONCLUSION: PLHIV were more optimistic about the potential for HIV cure. HHP had more direct experience with HIV cure-focused studies. Educational strategies are required for both groups to increase understanding around ATIs in HIV cure research but should be tailored specifically to each group.

Eptinezumab for the Prevention of Episodic Migraine: Sustained Effect Through 1 Year of Treatment in the PROMISE-1 Study.

PURPOSE: The Prevention of Migraine via Intravenous ALD403 Safety and Efficacy 1 (PROMISE-1) study was a phase III, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, tolerability, and pharmacokinetic properties of repeat intravenous (IV) doses of the calcitonin gene-related peptide‒targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with episodic migraine. Here we present the results of PROMISE-1 through 1 year of treatment (up to 4 doses). METHODS: Patients received up to 4 IV administrations of eptinezumab 30 mg, 100 mg, 300 mg, or placebo every 12 weeks. Patients recorded migraine and headache in an electronic diary daily. Additional assessments, including the patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 56-week study period. FINDINGS: A total of 888 adults (mean age, 39.8 years; 84.3% female; 83.8% white) received treatment: eptinezumab 30 mg, n = 219; eptinezumab 100 mg, n = 223; eptinezumab 300 mg, n = 224; and placebo, n = 222. During the primary 12-week study evaluation period, single doses of eptinezumab 100 mg and 300 mg led to significant reductions in mean monthly migraine-days versus placebo, beginning as early as the first day after the initial dose. The reduction in mean monthly migraine-days was maintained throughout the study (100 mg, -3.9, -4.5, -4.7, and -4.5 days; 300 mg, -4.3, -4.8, -5.1, and -5.3 days; and placebo, -3.2, -3.8, -4.0, and -4.0 days during weeks 1-12, 13-24, 25-36, and 37-48, respectively). Overall, the number of patients with a ≥50% or ≥75% reduction in migraine for each 12-week interval during the entire study was consistently numerically higher in the eptinezumab groups than in the placebo group. The proportions of patients with ≥50% reduction in migraine were similar across the eptinezumab groups. Eptinezumab was well tolerated throughout the study. Adverse events were similar across dosing periods, and there were no serious tolerability signals identified with continued dosing. IMPLICATIONS: IV eptinezumab administered every 12 weeks for up to 4 doses was associated with early and sustained migraine-preventive effects and a favorable safety profile in adults with episodic migraine. ClinicalTrials.gov identifier: NCT02559895.