Examining the feasibility of assisted index case testing for HIV case-finding: a qualitative analysis of barriers and facilitators to implementation in Malawi.

BACKGROUND: Assisted index case testing (ICT), in which health care workers take an active role in referring at-risk contacts of people living with HIV for HIV testing services, has been widely recognized as an evidence-based intervention with high potential to increase status awareness in people living with HIV. While the available evidence from eastern and southern Africa suggests that assisted ICT can be an effective, efficient, cost-effective, acceptable, and low-risk strategy to implement in the region, it reveals that feasibility barriers to implementation exist. This study aims to inform the design of implementation strategies to mitigate these feasibility barriers by examining "assisting" health care workers' experiences of how barriers manifest throughout the assisted ICT process, as well as their perceptions of potential opportunities to facilitate feasibility. METHODS: In-depth interviews were conducted with 26 lay health care workers delivering assisted ICT in Malawian health facilities. Interviews explored health care workers' experiences counseling index clients and tracing these clients' contacts, aiming to inform development of a blended learning implementation package. Transcripts were inductively analyzed using Dedoose coding software to identify and describe key factors influencing feasibility of assisted ICT. Analysis included multiple rounds of coding and iteration with the data collection team. RESULTS: Participants reported a variety of barriers to feasibility of assisted index case testing implementation, including sensitivities around discussing ICT with clients, privacy concerns, limited time for assisted index case testing amid high workloads, poor quality contact information, and logistical obstacles to tracing. Participants also reported several health care worker characteristics that facilitate feasibility (knowledge, interpersonal skills, non-stigmatizing attitudes and behaviors, and a sense of purpose), as well as identified process improvements with the potential to mitigate barriers. CONCLUSIONS: Maximizing assisted ICT's potential to increase status awareness in people living with HIV requires equipping health care workers with effective training and support to address and overcome the many feasibility barriers that they face in implementation. Findings demonstrate the need for, as well as inform the development of, implementation strategies to mitigate barriers and promote facilitators to feasibility of assisted ICT. TRIAL REGISTRATION: NCT05343390. Date of registration: April 25, 2022.

Does a blended learning implementation package enhance HIV index case testing in Malawi? A protocol for a cluster randomised controlled trial.

INTRODUCTION: Index case testing (ICT) is an evidence-based approach that efficiently identifies persons in need of HIV treatment and prevention services. In Malawi, delivery of ICT has faced challenges due to limited technical capacity of healthcare workers (HCWs) and clinical coordination. Digitisation of training and quality improvement processes presents an opportunity to address these challenges. We developed an implementation package that combines digital and face-to-face modalities (blended learning) to strengthen HCWs ICT skills and enhance quality improvement mechanisms. This cluster randomised controlled trial will assess the impact of the blended learning implementation package compared with the standard of care (SOC) on implementation, effectiveness and cost-effectiveness outcomes. METHODS AND ANALYSIS: The study was conducted in 33 clusters in Machinga and Balaka districts, in Southern Malawi from November 2021 to November 2023. Clusters are randomised in a 2:1 ratio to the SOC versus blended learning implementation package. The SOC is composed of: brief face-to-face HCW ICT training and routine face-to-face facility mentorship for HCWs. The blended learning implementation package consists of blended teaching, role-modelling, practising, and providing feedback, and blended quality improvement processes. The primary implementation outcome is HCW fidelity to ICT over 1 year of follow-up. Primary service uptake outcomes include (a) index clients who participate in ICT, (b) contacts elicited, (c) HIV self-test kits provided for secondary distribution, (d) contacts tested and (e) contacts identified as HIV-positive. Service uptake analyses will use a negative binomial mixed-effects model to account for repeated measures within each cluster. Cost-effectiveness will be assessed through incremental cost-effectiveness ratios examining the incremental cost of each person tested. ETHICS AND DISSEMINATION: The Malawi National Health Science Research Committee, the University of North Carolina and the Baylor College of Medicine Institutional Review Boards approved the trial. Study findings will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05343390.

Phone-based psychosocial counseling for people living with HIV: Feasibility, acceptability and impact on uptake of psychosocial counseling services in Malawi.

People living with HIV experience psychosocial needs that often are not addressed. We designed an innovative low-resource model of phone-based psychosocial counseling (P-PSC). We describe cohort characteristics, acceptability, feasibility and utilization of P-PSC at health facilities supported by Baylor Foundation Malawi. Staff were virtually oriented at 120 sites concurrently. From facility-based phones, people with new HIV diagnosis, high viral load, treatment interruption or mental health concerns were referred without identifiable personal information to 13 psychosocial counselors via a WhatsApp group. Routine program data were retrospectively analyzed using univariate approaches and regressions with interrupted time series analyses. Clients utilizing P-PSC were 63% female, 25% youth (10-24 y) and 9% children (<10 y). They were referred from all 120 supported health facilities. Main referral reasons included new HIV diagnosis (32%), ART adherence support (32%) and treatment interruption (21%). Counseling was completed for 99% of referrals. Counseling sessions per month per psychosocial counselor increased from 77 before P-PSC to 216 in month 1 (95% CI = 82, 350, p = 0.003). Total encounters increased significantly to 31,642 in year 1 from ~6,000 during the 12 prior months, an over fivefold increase. P-PSC implementation at 120 remote facilities was acceptable and feasible with immediate, increased utilization despite few psychosocial counselors in Malawi.

Examining the feasibility of assisted index case testing for HIV case-finding: a qualitative analysis of barriers and facilitators to implementation in Malawi.

Background: Assisted index case testing, in which health care workers take an active role in referring at-risk contacts of people living with HIV for HIV testing services, has been widely recognized as an evidence-based intervention with high potential to increase PLHIV status awareness. Promising evidence for the approach has led to several attempts to scale assisted index case testing throughout eastern and southern Africa in recent years. However, despite effective implementation being at the heart of any assisted index case testing strategy, there is limited implementation science research from the perspective of the HCWs who are doing the "assisting". This study examines the feasibility of assisted index case testing from the perspective of health care workers implementing the approach in Malawi. Methods: In-depth interviews were conducted with 26 lay health care workers delivering assisted index case testing in Malawian health facilities. Interviews explored health care workers' experiences counselling index clients and tracing these clients' contacts, aiming to inform development of a blended learning implementation package. Transcripts were inductively analyzed using Dedoose coding software to identify and describe key factors influencing feasibility of assisted index case testing. Analysis included multiple rounds of coding and iteration with the data collection team. Results: Participants reported a variety of barriers to feasibility of assisted index case testing implementation, including privacy concerns, limited time for assisted index case testing amid high workloads, poor quality contact information, logistical obstacles to tracing, and challenges of discussing sexual behavior with clients. Participants also reported several health care worker characteristics that facilitate feasibility: robust understanding of assisted index case testing's rationale and knowledge of procedures, strong interpersonal skills, positive attitudes towards clients, and sense of purpose in their work. Conclusions: Findings demonstrate that maximizing assisted index case testing's potential to increase HIV status awareness requires adequately equipping health care workers with appropriate knowledge, skills, and support to address and overcome the many feasibility challenges that they face in implementation. Trial Registration Number: NCT05343390 Date of registration: April 25, 2022.

Intervention Fidelity to VITAL Start (Video Intervention to Inspire Treatment Adherence for Life) in a Randomized Controlled Trial Among Women Living With HIV in Malawi.

BACKGROUND: Intervention effectiveness in a randomized controlled trial is attributed to intervention fidelity. Measuring fidelity has increasing significance to intervention research and validity. The purpose of this article is to describe a systematic assessment of intervention fidelity for VITAL Start (Video intervention to Inspire Treatment Adherence for Life)-a 27-minute video-based intervention designed to improve antiretroviral therapy adherence among pregnant and breastfeeding women. METHOD: Research Assistants (RAs) delivered VITAL Start to participants after enrolment. The VITAL Start intervention had three components: a pre-video orientation, video viewing, and post-video counseling. Fidelity assessments using checklists comprised self (RA assessment) and observer (Research Officers, also known as ROs) assessment. Four fidelity domains (adherence, dose, quality of delivery, and participant responsiveness) were evaluated. Score scale ranges were 0 to 29 adherence, 0 to 3 dose, 0 to 48 quality of delivery and 0 to 8 participant responsiveness. Fidelity scores were calculated. Descriptive statistics summarizing the scores were performed. RESULTS: In total, eight RAs delivered 379 VITAL Start sessions to 379 participants. Four ROs observed and assessed 43 (11%) intervention sessions. The mean scores were 28 (SD = 1.3) for adherence, 3 (SD = 0) for dose, 40 (SD = 8.6) for quality of delivery, and 10.4 (SD = 1.3) for participant responsiveness. CONCLUSION: Overall, the RAs successfully delivered the VITAL Start intervention with high fidelity. Intervention fidelity monitoring should be an important element of randomized control trial design of specific interventions to ensure having reliable study results.

The prevalence, incidence, and recurrence of intimate partner violence and its association with adverse childhood experiences among pregnant and breastfeeding women living with HIV in Malawi.

Background: Intimate partner violence (IPV) is associated with suboptimal HIV treatment outcomes, but its distribution and risk factors among certain subpopulations of people living with HIV in resource-limited settings are not well known. We examined the prevalence, incidence, and recurrence of IPV and its association with adverse childhood experiences (ACEs) among pregnant/breastfeeding women living with HIV in Malawi. Methods: This study used longitudinal data for 455 pregnant women living with HIV continuously enrolled in the VITAL Start trial. IPV was assessed at baseline and months 1, 6, and 12 using the widely validated WHO IPV survey. Forms of IPV assessed were physical IPV, emotional IPV, and sexual IPV measured as prevalence, incidence, and recurrence. ACE histories were assessed using WHO's ACE International Questionnaire (ACE-IQ) tool. Logistic and log-binomial regressions were used in multivariable analyses that controlled for factors such as depression and alcohol use. Results: Participants' mean age was 27.6 ± 5.7 years. Forty-three percent (43%) reported IPV prevalence, 13% reported IPV incidence, and another 13% reported IPV recurrence, with emotional IPV being the most commonly reported IPV type. Over 96% reported experiencing ⩾1 ACE. In regression analysis, cumulative ACE scores were significantly associated with IPV prevalence and IPV recurrence and in both cases, the magnitude of association was greatest for sexual IPV compared with physical IPV and emotional IPV. ACE scores were not significantly associated with IPV incidence. Conclusions: IPV is highly prevalent among pregnant women living with HIV and continues to occur throughout the pregnancy and postpartum period; its graded relationship with ACEs is a concern in resource-limited settings where HIV/AIDS remains a public health concern. Strategies aimed to address the needs of pregnant/breastfeeding women living with HIV may benefit from the regular screening of this population for IPV and ACE, including in antenatal care clinics.

The relationship between adverse childhood experiences and common mental disorders among pregnant women living with HIV in Malawi.

INTRODUCTION: Adverse childhood experiences (ACEs) have been linked to common mental disorders (CMDs) such as anxiety and depressive thoughts. We examined the prevalence of ACEs and their association with CMDs among pregnant women living with HIV (PWLHIV) in Malawi-an HIV endemic resource-limited setting. METHODS: This is a cross-sectional study of 798 PWLHIV enrolled in the VITAL Start trial in Malawi (10/2018 to 06/2021) (NCT03654898). ACE histories were assessed using WHO's Adverse Childhood Experiences International Questionnaire (ACE-IQ) tool. Depressive symptoms (somatic complaints, reduced vital energy, anxiety, and depressive thoughts) were assessed using WHO's Self Reporting Questionnaire 20-Item (SRQ-20) tool. Log-binomial regressions were used to examine the association between cumulative ACEs and each depressive symptom, as well as identify ACEs driving this association. RESULTS: The mean age of our sample was 27.5 years. Over 95 % reported having experienced ≥1 ACE. On average, each participant reported four ACEs; 11 % reported sexual abuse. About 52 % and 44 % reported anxiety and depressive thoughts, respectively. In regressions, cumulative ACE scores were significantly associated with depressive symptoms-even after adjusting for multiple testing. This association was primarily driven by reports of sexual abuse. LIMITATIONS: Data on maternal ACEs were self-reported and could suffer from measurement error because of recall bias. CONCLUSIONS: ACEs are widespread and have a graded relationship with depressive symptoms in motherhood. Sexual abuse was found to be a primary driver of this association. Earlier recognition of ACEs and provision of trauma-informed interventions to improve care in PWLHIV may reduce negative mental health sequelae.

Development of a Blended Learning Approach to Delivering HIV-Assisted Contact Tracing in Malawi: Applied Theory and Formative Research.

BACKGROUND: Despite progress toward the Joint United Nations Programme on HIV/AIDS "95-95-95" targets (95% of HIV-positive persons tested, 95% of tested persons on treatment, and 95% of treated persons virally suppressed), a gap remains in achieving the first 95% target. Assisted contact tracing (ACT), in which health workers support HIV-positive index clients to recruit their contacts (sexual partners and children) for HIV testing, efficiently identifies HIV-positive persons in need of treatment. Although many countries, including Malawi, began implementing ACT, testing outcomes in routine settings have been worse than those in trial settings. OBJECTIVE: The aim of this paper is to use formative research and frameworks to develop and digitize an implementation package to bridge the gap between ACT research and practice. METHODS: Semistructured qualitative research was conducted in 2019 in Malawi with key informants. Barriers and facilitators to intervention delivery were identified using the Consolidated Framework for Implementation Research. Approaches to digitization were examined using human-centered design principles. RESULTS: Limited clinic coordination and health worker capacity to address the complexities of ACT were identified as barriers. Ongoing individual training consisting of learning, observing, practicing, and receiving feedback, as well as group problem-solving were identified as facilitators. Important features of digitization included (1) culturally relevant visual content, (2) capability of offline use, and (3) simple designs and basic editing to keep costs low. CONCLUSIONS: Formative research and frameworks played a key role in designing and digitizing an implementation package for ACT delivery in a low-income setting such as Malawi.

Pilot-Testing a Blended Learning Package for Health Care Workers to Improve Index Testing Services in Southern Malawi: An Implementation Science Study.

BACKGROUND: HIV index testing, an intervention in which HIV-positive "indexes" (persons diagnosed with HIV) are supported to recruit their "contacts" (sexual partners and children) efficiently identifies HIV-infected persons in need of treatment and HIV-uninfected persons in need of prevention. However, index testing implementation in sub-Saharan African health care settings has been suboptimal. The objective of this study was to develop and pilot test a blended learning capacity-building package to improve index testing implementation in Malawi. METHODS: In 2019, a blended learning package combining digital and face-to-face training modalities was field tested at 6 health facilities in Mulanje, Malawi using a pre-/post- type II hybrid design with implementation and effectiveness outcomes. Health care worker (HCW) fidelity to the intervention was assessed via observed encounters before and after the training. Preliminary effectiveness was examined by comparing index testing program indicators in the 2 months before and 4 months after the training. Indicators included the mean number of indexes screened, contacts elicited, and contacts who received HIV testing per facility per month. RESULTS: On a 30-point scale, HCW fidelity to index testing protocols improved from 6.0 pre- to 25.5 post-package implementation (P = 0.002). Index testing effectiveness indicators also increased: indexes screened (pre = 63, post = 101, P < 0.001); contacts elicited (pre = 75, post = 131, P < 0.001); and contacts who received HIV testing (pre = 27, post = 41, P = 0.014). CONCLUSIONS: The blended learning package improved fidelity to index testing protocols and preliminary effectiveness outcomes. This package has the potential to enhance implementation of HIV index testing approaches, a necessary step for ending the HIV epidemic.

Community-facility linkage models and maternal and infant health outcomes in Malawi's PMTCT/ART program: A cohort study.

BACKGROUND: In sub-Saharan Africa, 3 community-facility linkage (CFL) models-Expert Clients, Community Health Workers (CHWs), and Mentor Mothers-have been widely implemented to support pregnant and breastfeeding women (PBFW) living with HIV and their infants to access and sustain care for prevention of mother-to-child transmission of HIV (PMTCT), yet their comparative impact under real-world conditions is poorly understood. METHODS AND FINDINGS: We sought to estimate the effects of CFL models on a primary outcome of maternal loss to follow-up (LTFU), and secondary outcomes of maternal longitudinal viral suppression and infant "poor outcome" (encompassing documented HIV-positive test result, LTFU, or death), in Malawi's PMTCT/ART program. We sampled 30 of 42 high-volume health facilities ("sites") in 5 Malawi districts for study inclusion. At each site, we reviewed medical records for all newly HIV-diagnosed PBFW entering the PMTCT program between July 1, 2016 and June 30, 2017, and, for pregnancies resulting in live births, their HIV-exposed infants, yielding 2,589 potentially eligible mother-infant pairs. Of these, 2,049 (79.1%) had an available HIV treatment record and formed the study cohort. A randomly selected subset of 817 (40.0%) cohort members underwent a field survey, consisting of a questionnaire and HIV biomarker assessment. Survey responses and biomarker results were used to impute CFL model exposure, maternal viral load, and early infant diagnosis (EID) outcomes for those missing these measures to enrich data in the larger cohort. We applied sampling weights in all statistical analyses to account for the differing proportions of facilities sampled by district. Of the 2,049 mother-infant pairs analyzed, 62.2% enrolled in PMTCT at a primary health center, at which time 43.7% of PBFW were ≤24 years old, and 778 (38.0%) received the Expert Client model, 640 (31.2%) the CHW model, 345 (16.8%) the Mentor Mother model, 192 (9.4%) ≥2 models, and 94 (4.6%) no model. Maternal LTFU varied by model, with LTFU being more likely among Mentor Mother model recipients (adjusted hazard ratio [aHR]: 1.45; 95% confidence interval [CI]: 1.14, 1.84; p = 0.003) than Expert Client recipients. Over 2 years from HIV diagnosis, PBFW supported by CHWs spent 14.3% (95% CI: 2.6%, 26.1%; p = 0.02) more days in an optimal state of antiretroviral therapy (ART) retention with viral suppression than women supported by Expert Clients. Infants receiving the Mentor Mother model (aHR: 1.24, 95% CI: 1.01, 1.52; p = 0.04) and ≥2 models (aHR: 1.44, 95% CI: 1.20, 1.74; p < 0.001) were more likely to undergo EID testing by age 6 months than infants supported by Expert Clients. Infants receiving the CHW and Mentor Mother models were 1.15 (95% CI: 0.80, 1.67; p = 0.44) and 0.84 (95% CI: 0.50, 1.42; p = 0.51) times as likely, respectively, to experience a poor outcome by 1 year than those supported by Expert Clients, but not significantly so. Study limitations include possible residual confounding, which may lead to inaccurate conclusions about the impacts of CFL models, uncertain generalizability of findings to other settings, and missing infant medical record data that limited the precision of infant outcome measurement. CONCLUSIONS: In this descriptive study, we observed widespread reach of CFL models in Malawi, with favorable maternal outcomes in the CHW model and greater infant EID testing uptake in the Mentor Mother model. Our findings point to important differences in maternal and infant HIV outcomes by CFL model along the PMTCT continuum and suggest future opportunities to identify key features of CFL models driving these outcome differences.

Scalable graphene electro-optical modulators for all-fibre pulsed lasers.

Recently, graphene electro-optical modulators have emerged as a viable alternative to the conventional modulators due to their broadband operation, ultrafast responsivity, small footprint, and low energy consumption. Here, we report scalable graphene electro-optical modulators for all-fibre pulsed laser applications. An actively Q-switched all-fibre laser is demonstrated with a scalable graphene electro-optical modulator for the first time, which is different from the previously reported work that typically implemented graphene electro-optical modulators in a free-space optical system. Our electrically modulated actively Q-switched fibre laser outputs at the centre wavelength of ∼1961.9 nm, the tunable repetition rate of 56.5 to 62.5 kHz, the maximum pulse energy of ∼80 nJ, and the signal-to-noise ratio of ∼46.6 dB. This work demonstrates that the scalable all-fibre integrated graphene electro-optical modulator approach is promising for producing pulsed fibre lasers at 2 µm with high performance and easy integration which are useful in various applications such as medical treatment, material processing, and spectroscopy.

Treatment with the direct oral anticoagulants (DOACs) apixaban and rivaroxaban associated with significant worsening of behavioural and psychological symptoms of dementia (BPSD).

We report the cases of two patients who developed worsening behavioural and psychological symptoms of dementia (BPSD), coinciding with starting the factor Xa inhibitor direct oral anticoagulant medications apixaban and rivaroxaban, respectively. Both patients required detaining under the Mental Health Act. Their symptoms improved significantly, within 2 weeks, on switching to alternative anticoagulant therapies and they were both discharged from the acute psychiatric ward. Front-line staff should partake in postmarketing surveillance of medications, completing the Medicines and Healthcare products Regulatory Agency yellow cards for example (UK). There is increasing evidence for an aetiological role of cerebral mitochondrial dysfunction in neuropsychiatric disorders. Development of a rating scale of drugs that are potentially less toxic to cerebral mitochondria could inform national prescribing guidelines and enable safer treatments to be offered to older people, reducing the likely hood of them experiencing apparent BPSD.

Video-Based Intervention for Improving Maternal Retention and Adherence to HIV Treatment: Patient Perspectives and Experiences.

VITAL Start is a video-based intervention aimed to improve maternal retention in HIV care and adherence to antiretroviral therapy (ART) in Malawi. We explored the experiences of pregnant women living with HIV (PWLHIV) not yet on ART who received VITAL Start before ART initiation to assess the intervention's acceptability, feasibility, fidelity of delivery, and perceived impact. Between February and September 2019, we conducted semi-structured interviews with a convenience sample of 34 PWLHIV within one month of receiving VITAL Start. The participants reported that VITAL Start was acceptable and feasible and had good fidelity of delivery. They also reported that the video had a positive impact on their lives, encouraging them to disclose their HIV status to their sexual partners who, in turn, supported them to adhere to ART. The participants suggested using a similar intervention to provide health-related education/counseling to people with long term conditions. Our findings suggest that video-based interventions may be an acceptable, feasible approach to optimizing ART retention and adherence amongst PWLHIV, and they can be delivered with high fidelity. Further exploration of the utility of low cost, scalable, video-based interventions to address health counseling gaps in sub-Saharan Africa is warranted.

The relationship between intimate partner violence and HIV outcomes among pregnant women living with HIV in Malawi.

Background: Intimate partner violence (IPV) is a global public health concern particularly in pregnancy where IPV can have negative health implications for the mother and child. Data suggest IPV disproportionately affects pregnant women living with HIV (PWLWH) compared to those without HIV. HIV-related outcomes are worse among women experiencing IPV. Despite this knowledge, there is paucity of data concerning PWLWH and IPV in Malawi, where there is a high HIV prevalence (10.6%). Objectives: We aim to characterize IPV amongst PWLWH in Malawi and describe its relationship to demographic characteristics, psychosocial factors, and HIV-related outcomes. Methods: This analysis used data from the VITAL Start pilot study, which is a video-based intervention targeting retention and ART adherence amongst PWLWH in Malawi. PWLWH not on ART were recruited at antenatal clinic and given study questionnaires to assess demographics, IPV, and psychosocial factors. Questionnaires were also administered at one-month follow-up to assess outcomes related to HIV. Descriptive statistics and logistic regression models were used to explore the risk factors associated with IPV. Results: Thirty-nine percent of participants reported ever experiencing IPV from their current partner. The majority (53%) reporting IPV experienced more than one type of violence. IPV was associated with being married (p=0.04) and depression (p<0.0001) in the univariable analysis. For women retained at one-month, IPV was associated with reporting a missed ART dose in the past month but not with adherence measured by pill count. Conclusions: A large proportion of PWLWH experienced IPV from their current partner and IPV was associated with worse self-reported ART adherence at one-month follow-up. Further evidence is needed to understand how IPV impacts PWLWH throughout postpartum and beyond. Given the detrimental impact on health outcomes among PWLWH in Malawi, additional focus on IPV is essential to identify mechanisms to prevent, screen, and manage IPV among this population.

Structural and functional characterization of recombinant human growth hormone isolated from transgenic pig milk.

This study aimed to establish and reproduce transgenic pigs expressing human growth hormone (hGH) in their milk. We also aimed to purify hGH from the milk, to characterize the purified protein, and to assess the potential of our model for mass production of therapeutic proteins using transgenic techniques. Using ~15.5 L transgenic pig milk, we obtained proteins with ≥ 99% purity after three pre-treatments and five column chromatography steps. To confirm the biosimilarity of our milk-derived purified recombinant hGH (CGH942) with commercially available somatropin (Genotropin), we performed spectroscopy, structural, and biological analyses. We observed no difference between the purified protein and Genotropin samples. Furthermore, rat models were used to assess growth promotion potential. Our results indicate that CGH942 promotes growth, by increasing bone development and body weight. Toxicity assessments revealed no abnormal findings after 4 weeks of continuous administration and 2 weeks of recovery. The no-observed-adverse-effect level for both males and females was determined to be 0.6 mg/kg/day. Thus, no toxicological differences were observed between commercially available somatropin and CGH942 obtained from transgenic pig milk. In conclusion, we describe a transgenic technique using pigs, providing a new platform to produce human therapeutic proteins.

Management of light and scattering in InP NWs by dielectric polymer shell.

Understanding and management of light is of great importance for nanoscale devices. This report demonstrates enhanced absorption, photoluminescence and scattering in InP nanowires when coated with dielectric polymer shell. The shells increase absorption and emission by a factor of ∼2 and photoluminescence by a factor of ∼4. A thorough optical characterization is provided, including reflectance, transmission, luminescence and scattering to incident and transmitted directions. From this characterization, we derive the distribution of absorbed light within the structure (InP nanowires, Au seed particles and the substrate). Additionally, reflectance, transmission and emission are shown to become increasingly diffuse with the dielectric shells. The results are thought to provide better understanding in light-matter interaction in nanostructures, as well as to provide valuable tools for light and scattering management in nanoscale optoelectronics.

The Video intervention to Inspire Treatment Adherence for Life (VITAL Start): protocol for a multisite randomized controlled trial of a brief video-based intervention to improve antiretroviral adherence and retention among HIV-infected pregnant women in Malawi.

BACKGROUND: Improving maternal antiretroviral therapy (ART) retention and adherence is a critical challenge facing prevention of mother-to-child transmission (PMTCT) of HIV programs. There is an urgent need for evidence-based, cost-effective, and scalable interventions to improve maternal adherence and retention that can be feasibly implemented in overburdened health systems. Brief video-based interventions are a promising but underutilized approach to this crisis. We describe a trial protocol to evaluate the effectiveness and implementation of a standardized educational video-based intervention targeting HIV-infected pregnant women that seeks to optimize their ART retention and adherence by providing a VITAL Start (Video intervention to Inspire Treatment Adherence for Life) before committing to lifelong ART. METHODS: This study is a multisite parallel group, randomized controlled trial assessing the effectiveness of a brief facility-based video intervention to optimize retention and adherence to ART among pregnant women living with HIV in Malawi. A total of 892 pregnant women living with HIV and not yet on ART will be randomized to standard-of-care pre-ART counseling or VITAL Start. The primary outcome is a composite of retention and adherence (viral load < 1000 copies/ml) 12 months after starting ART. Secondary outcomes include assessments of behavioral adherence (self-reported adherence, pharmacy refill, and tenofovir diphosphate concentration), psychosocial impact, and resource utilization. We will also examine the implementation of VITAL Start via surveys and qualitative interviews with patients, partners, and health care workers and conduct cost-effectiveness analyses. DISCUSSION: This is a robust evaluation of an innovative facility-based video intervention for pregnant women living with HIV, with the potential to improve maternal and infant outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03654898. Registered on 31 August 2018.

Factors associated with burnout amongst healthcare workers providing HIV care in Malawi.

CONTEXT: High rates of burnout have been reported in low and medium income countries and can detrimentally impact healthcare delivery. Understanding factors associated with burnout amongst health care workers providing HIV care may help develop interventions to prevent/treat burnout. OBJECTIVES: We sought to understand factors associated with burnout amongst health care workers providing HIV care in Malawi. METHODS: This was a sub-study of a larger cross-sectional study measuring burnout prevalence amongst a convenience sample of healthcare workers providing HIV care in 89 health facilities in eight districts in Malawi. Burnout was measured using the Maslach Burnout Inventory. Anonymously administered surveys included questions about sociodemographics, work characteristics (work load, supervisor support, team interactions), depression, life stressors, assessment of type D personality, and career satisfaction. We performed univariable and multivariable regression analyses to explore associations between variables and burnout. RESULTS: We received 535 responses (response rate 99%). Factors associated with higher rates of burnout on multivariable regression analyses included individual level factors: male gender (OR 1.75 [CI 1.17, 2.63]; p = 0.007), marital status (widowed or divorced) (OR 3.24 [CI 1.32, 7.98]; p = 0.011), depression (OR 3.32 [CI 1.21, 9.10]; p = 0.020), type D personality type (OR 2.77 [CI 1.50, 5.12]; p = 0.001) as well as work related factors: working at a health center vs. a rural hospital (OR 2.02 [CI 1.19, 3.40]; p = 0.009); lack of a very supportive supervisor (OR 2.38 [CI 1.32, 4.29]; p = 0.004), dissatisfaction with work/team interaction (OR 1.76 [CI 1.17, 2.66]; p = 0.007), and career dissatisfaction (OR 0.76 [CI 0.60, 0.96]; p = 0.020). CONCLUSION: This study identified several individual level vulnerabilities as well as work related modifiable factors. Improving the supervisory capacity of health facility managers and creating conditions for improved team dynamics may help reduce burnout amongst healthcare workers proving HIV care in Malawi.

Prioritising the most needed paediatric antiretroviral formulations: the PADO4 list.

Despite considerable progress in paediatric HIV treatment and timely revision of global policies recommending the use of more effective and tolerable antiretroviral regimens, optimal antiretroviral formulations for infants, children, and adolescents remain limited. The Paediatric Antiretroviral Drug Optimization group reviews medium-term and long-term priorities for antiretroviral drug development to guide industry and other stakeholders on formulations most needed for low-income and middle-income countries. The group convened in December, 2018, to assess progress since the previous meeting and update the list of priority formulations. Issues relating to drug optimisation for neonatal prophylaxis and paediatric treatment, and those relating to the investigation of novel antiretrovirals in adolescents and pregnant and lactating women were also discussed. Continued focus on identifying, prioritising, and providing access to optimal antiretroviral formulations suitable for infants, children, and adolescents is key to ensuring that global HIV treatment targets can be met.

VITAL Start: Video-Based Intervention to Inspire Treatment Adherence for Life-Pilot of a Novel Video-Based Approach to HIV Counseling for Pregnant Women Living with HIV.

We developed and piloted a video-based intervention targeting HIV-positive pregnant women to optimize antiretroviral therapy (ART) retention and adherence by providing a VITAL Start (Video-intervention to Inspire Treatment Adherence for Life) before ART. VITAL Start (VS) was grounded in behavior-determinant models and developed through an iterative multi-stakeholder process. Of 306 pregnant women eligible for ART, 160 were randomized to standard of care (SOC), 146 to VS and followed for one-month. Of those assigned to VS, 100% completed video-viewing; 96.5% reported they would recommend VS. Of 11 health workers interviewed, 82% preferred VS over SOC; 91% found VS more time-efficient. Compared to SOC, VS group had greater change in HIV/ART knowledge (p < 0.01), trend towards being more likely to start ART (p = 0.07), and better self-reported adherence (p = 0.02). There were no significant group differences in 1-month retention and pharmacy pill count. VITAL Start was highly acceptable, feasible, with promising benefits to ART adherence.