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BACKGROUND Despite significant investments in Ending the HIV Epidemic, disparities in HIV care persist and there is an urgent need to evaluate novel and scalable approaches to improving HIV care engagement and viral suppression in real-world settings. OBJECTIVE To describe a study protocol for a pragmatic type II hybrid effectiveness-implementation randomized controlled trial comparing existing standard of care clinic HIV linkage, adherence and retention (LAR) protocols to a mobile Health (mHealth)-enhanced linkage, adherence, and retention (mLAR) intervention. METHODS 500 participants will be enrolled into the study from clinics in Baltimore City. Eligibility criteria includes age ≥ 18 years of age and 1. new HIV diagnosis or 2. HIV-infected and out of care or 3. HIV-infected and deemed by clinic staff as someone who could benefit from linkage and retention services. Participants randomized to the intervention receive mHealth-supported patient navigation for 12 months. Participants in the control group receive the referring clinic’s standard of care patient support. The primary outcome is HIV virologic suppression at 12 months. A subset of participants will be interviewed at 12 months to learn about their HIV care experiences and, for those in the intervention arm, their experiences with the mLAR intervention. This protocol was developed in collaboration with the Baltimore City Health Department (BCHD) and the Maryland Department of Health (MDH), and with input from a community advisory board. RESULTS Enrollment began on February 25, 2020. As of August 11, 2022, 411 of the 500 target participants had been enrolled. CONCLUSIONS Pragmatic implementation science trials designed with input from key stakeholders, including health department and community members, can help evaluate the evidence for mHealth interventions to reduce HIV health disparities. CLINICALTRIAL NCT 03934437

BACKGROUND: Achieving the 90–90–90 targets for tuberculosis (TB) will require interventions that enhance diagnosis, linkage, treatment and adherence to care. As a first step in the process, our team designed a suite of smartphone applications known as miLINC to improve time from diagnosis to treatment initiation in drug-resistant TB patients.SETTING: Three clinical locations in a large, peri-urban district in KwaZulu-Natal, South Africa.OBJECTIVE: To assess the acceptability, feasibility and impact of the miLINC mobile health applications as a solution to reducing the time from presentation to treatment initiation of rifampicin-resistant (RR) TB patients.METHODS: We used a prospective, observational quality improvement evaluation of miLINC's impact among newly diagnosed patients with RR-TB.RESULTS: A convenience sample comprising details of 6341 patients with presumptive TB were entered into miLINC. Of the 631 TB-positive sputum specimens, 41 (6.5%) were found to be RR-TB. The mean time from clinical presentation to RR-TB treatment initiation was 3 days, 21 h, 17 min.CONCLUSION: This is the first study to suggest that the time from presentation to diagnosis and to treatment initiation for patients with RR-TB can be significantly improved using an integrated approach combining technology with appropriate human resources.

Summary Antiretroviral agents with long-acting properties have potential to improve treatment outcomes substantially for people living with HIV. In November 2017, the Long acting/Extended Release Antiretroviral Resource Program (LEAP) convened a workshop with the aim of shaping the research agenda and promoting early development of long-acting or extended release products for key populations: pregnant and lactating women, children aged up to 10 years, and adolescents aged 10–19 years. Goals included strategies and principles to ensure that the needs of children, adolescents, and pregnant and lactating women are considered when developing long-acting formulations. Research should focus not only on how best to transition long-acting products to these populations, but also on early engagement across sectors and among stakeholders. A parallel rather than sequential approach is needed when establishing adult, adolescent, and paediatric clinical trials and seeking regulatory approval. Pregnant and lactating women should be included in adult clinical trials. Adolescent-friendly trial design is needed to improve recruitment and retention of young people.

Introduction India’s national AIDS Control Organization implemented World Health Organization’s option B+ HIV prevention of mother‐to‐child transmission (PMTCT) guidelines in 2013. However, scalable strategies to improve uptake of new PMTCT guidelines to reduce new infection rates are needed. This study assessed impact of Mobile Health‐Facilitated Behavioral Intervention on the uptake of PMTCT services. Methods A cluster‐randomized trial of a mobile health (mHealth)‐supported behavioural training intervention targeting outreach workers (ORWs) was conducted in four districts of Maharashtra, India. Clusters (one Integrated Counselling and Testing Center (ICTC, n = 119), all affiliated ORWs (n = 116) and their assigned HIV‐positive pregnant/postpartum clients (n = 1191)) were randomized to standard‐of‐care (SOC) ORW training vs. the COMmunity home Based INDia (COMBIND) intervention – specialized behavioural training plus a tablet‐based mHealth application to support ORW‐patient communication and patient engagement in HIV care. Impact on uptake of maternal antiretroviral therapy at delivery, exclusive breastfeeding at six months, infant nevirapine prophylaxis, and early infant diagnosis at six months was assessed using multi‐level random‐effects logistic regression models. Results Of 1191 HIV‐positive pregnant/postpartum women, 884 were eligible for primary outcome assessment; 487 were randomized to COMBIND. Multivariable analyses identified no statistically significant differences in any primary outcome by study arm. COMBIND was associated with higher uptake of exclusive breastfeeding at two months (adjusted Odds Ratio (aOR), 2.10; 95% CI 1.06 to 4.15) and early infant diagnosis at six weeks (aOR, 2.19; 95% CI 1.05 to 3.98) than SOC. Conclusions The COMBIND intervention was easily integrated into India’s existing PMTCT programme and improved early uptake of two PMTCT components that require self‐motivated health‐seeking behaviour, thus providing preliminary evidence to support COMBIND as a potentially scalable PMTCT strategy. Further study would identify modifications needed to optimize other PMTCT outcomes.

The first long-acting formulations of HIV drugs are undergoing regulatory review for use in maintenance of viral suppression in people with HIV. Although these novel drug formulations could contribute greatly to HIV treatment and prevention efforts, their lack of activity against hepatitis B virus (HBV) could limit their global impact, particularly in populations with high burdens of both HIV and HBV. An urgent need for greater investment in research and development of long-acting drugs with dual activity against HIV and HBV exists. Access to long-acting HIV drug formulations with dual activity against HBV would be transformative and have a great impact on efforts to prevent, treat, and eradicate both of these important global epidemics.

BackgroundInternal medicine physicians are often the first providers to encounter patients with a new diagnosis of tuberculosis. Given the public health risks of missed tuberculosis cases, assessing internal medicine residents’ ability to diagnose tuberculosis is important.MethodsInternal medicine resident knowledge and practice patterns in pulmonary tuberculosis diagnosis at 7 academic hospitals were assessed utilizing (a) a 10-item validated pulmonary tuberculosis diagnosis assessment tool and (b) a retrospective chart review of 343 patients who underwent a pulmonary tuberculosis evaluation while admitted to a resident-staffed internal medicine or infectious disease service. Our primary outcomes were the mean score and percentage of correct responses per assessment tool question, and the percentage of patients who had Centers for Disease Control and Prevention–recommended tuberculosis diagnostic tests obtained.ResultsOf the 886 residents who received the assessment, 541 responded, yielding a response rate of 61%. The mean score on the assessment tool (SD) was 4.4 (1.6), and the correct response rate was 57% (311/541) or less on 9 of 10 questions. On chart review, each recommended test was obtained for ≤43% (148/343) of patients, other than chest x-ray (328/343; 96%). A nucleic acid amplification test was obtained for 18% (62/343) of patients, whereas 24% (83/343) had only 1 respiratory sample obtained. Twenty patients were diagnosed with tuberculosis.ConclusionsSignificant knowledge and practice gaps exist in internal medicine residents’ abilities to diagnose tuberculosis. As residents represent the future providers who will be evaluating patients with possible tuberculosis, such deficiencies must be addressed.

In vivo studies suggested the possibility of an IgE-dependent regulation of high-affinity (FcepsilonRI) IgE receptor expression on basophils. The current studies extend these observations to in vitro cultures of human basophils. Incubation of basophils for 3 to 4 weeks resulted in a slow dissociation of IgE antibody, during which time FcepsilonRI expression decreased, as measured by flow cytometry using the anti-FcepsilonRIalpha monoclonal antibody, 22E7, or by measuring FcRIalpha mass by Western blotting of whole-cell lysates. Culture of basophils with IgE resulted in upregulation of FcepsilonRIalpha expression by both flow cytometry and Western blotting of whole-cell lysates. Upregulation followed a linear time course during 2 weeks of culture. The relative increase in FcepsilonRIalpha density depended on the starting density; with starting densities of FcepsilonRIalpha of 10,000 to 170,000 per basophil, the upregulation varied 20- to 1.1-fold, respectively. Upregulation occurred in high-purity basophils, was not influenced by IgG at concentrations up to 1 mg/mL, and was inhibited by dimeric IgE. Heat-inactivated IgE was less effective and the monoclonal antibody CGP51901 that prevents IgE binding to FcepsilonRIalpha blocked the ability of IgE to induce upregulation. The dose-response curve for IgE-induced upregulation had an effective concentration50 of 230 ng/mL. Although the receptor through which IgE induces this upregulation is not yet known, several characteristics suggest that the upregulation is mediated by IgE interacting through FcepsilonRIalpha itself.

The International Telecommunication Union estimates that, in only four years (2007–2011), mobile broadband subscriptions in the developing world increased by more than tenfold: from 43 million to 458 million. Mobile de-vices and internet access are becoming increasingly necessary professional tools for health-care workers at all levels in developing countries. New fibre and wireless infrastructure, as well as the rapid growth of computer processing power, provide an unprecedented op-portunity to scale up health worker training and improve its quality, as well as to optimize health service delivery and strengthen health systems.Over the past 20 years, learning management systems have contributed greatly to the tremendous expansion of e-learning. The past five years have also seen an increase in massive open online courses. eHealth technologies, including electronic medical records, laboratory and pharmacy information systems, along with disease surveil-lance and supply chain information systems, are transforming health care. Mobile health (mHealth), which is the practice of medicine and public health supported by mobile devices, extends these systems to the most remote and inaccessible parts of the developing world. In addition, the same mobile devices used to optimize communica-tion and support front-line health-care workers can be used to deploy multi-media training programmes and clini -cal decision support tools. The social media and the development of com-munities of practice have yet to be fully mobilized to support health workforce capacity building. The use of the social media by health workers has several potential benefits. Some examples are crowdsourcing of educational content, translations and localization (i.e. ad-aptation of the content to a particular region), peer-to-peer learning, joint problem solving and reflective prac-tice. In addition, ICTs can strengthen communication between providers and patients, increase community support for health worker capacity building and heighten the demand for high-quality clinical services.E-learning tools can support cur-riculum development and course sched -uling and management in ways that are conducive to blended learning approaches and that take advantage of multiple learning environments. Such tools can also be linked with national health professional registration and licensure systems, as well as with health workforce planning, management and in-service training systems, to provide information and support to the health workforce throughout the health worker lifecycle. Following pre-service train-ing, ICTs can be used to optimize the work of a health-care provider – the use of electronic health records, clinical decision-making, supply chain manage -ment and service quality control are examples – and to facilitate mHealth communications, continuing education and the establishment of professional social networks.Training methods based on video conferencing, webcasting, recording, localization and playback of training can enable global access to the very best educators and are more cost-effective than standard face-to-face educational programmes. Interactive content pro-grammes that incorporate gaming and adaptive learning tools can also be used.

Distance learning is an important tool for training HIV health workers. However, there is limited evidence on design and evaluation of distance learning HIV curricula and tools. We therefore designed, implemented, and evaluated a distance learning course on HIV management for clinical care providers in India. After course completion, participant scores rose significantly from a pretest (78.4% mean correct) compared with the posttest (87.5%, P < .001). After course completion, participants were more likely to be confident in starting an initial antiretroviral (ARV) regimen, understanding ARV toxicities, encouraging patient adherence, diagnosing immune reconstitution syndrome, and monitoring patients on ARV medications ( P ≤ .05). All participants (100%) strongly agreed/agreed that they would recommend this course to others, and most of them (96%) strongly agreed/agreed that they would take a course in this format again. A pragmatic approach to HIV curriculum development and evaluation resulted in reliable learning outcomes, as well as learner satisfaction and improvement in knowledge.

Background: Current educational strategies to integrate HIV care into primary medical care in Central America have traditionally targeted managers or higher-level officials, rather than local health care workers (HCWs). We developed a complementary online and on-site interactive training program to reach local HCWs at the primary care level in underserved communities. Methods: The training program targeted physicians, nurses, and community HCWs with limited access to traditional onsite training in Panama, Nicaragua, Dominican Republic, and Guatemala. The curriculum focused on principles of HIV care and health systems using a tutor-supported blended educational approach of an 8-week online component, a weeklong on-site problem-solving workshop, and individualized project-based interventions. Results: Of 258 initially active participants, 225 (225/258=87.2%) successfully completed the online component and the top 200 were invited to the on-site workshop. Of those, 170 (170/200=85%) attended the on-site workshop. In total, 142 completed all three components, including the project phase. Quantitative and qualitative evaluation instruments included knowledge assessments, reflexive essays, and acceptability surveys. The mean pre and post-essay scores demonstrating understanding of social determinants, health system organization, and integration of HIV services were 70% and 87.5%, respectively, with an increase in knowledge of 17.2% (p,0.001). The mean pre- and post-test scores evaluating clinical knowledge were 70.9% and 90.3%, respectively, with an increase in knowledge of 19.4% (p,0.001). A survey of Likert scale and open-ended questions demonstrated overwhelming participant satisfaction with course content, structure, and effectiveness in improving their HIV-related knowledge and skills. Conclusion: This innovative curriculum utilized technology to target HCWs with limited access to educational resources. Participants benefited from technical skills acquired through the process, and could continue working within their underserved communities while participating in the online component and then implement interventions that successfully converted theoretical knowledge to action to improve integration of HIV care into primary care.

Background Distance learning may be useful for building health research capacity. However, evidence that it can improve knowledge and skills in health research, particularly in resource-poor settings, is limited. We compared the impact and acceptability of teaching two distinct content areas, Biostatistics and Research Ethics, through either on-line distance learning format or traditional on-site training, in a randomized study in India. Our objective was to determine whether on-line courses in Biostatistics and Research Ethics could achieve similar improvements in knowledge, as traditional on-site, classroom-based courses. Methods Subjects: Volunteer Indian scientists were randomly assigned to one of two arms. Intervention: Students in Arm 1 attended a 3.5-day on-site course in Biostatistics and completed a 3.5-week on-line course in Research Ethics. Students in Arm 2 attended a 3.5-week on-line course in Biostatistics and 3.5-day on-site course in Research Ethics. For the two course formats, learning objectives, course contents and knowledge tests were identical. Main Outcome Measures: Improvement in knowledge immediately and 3-months after course completion, compared to baseline. Results Baseline characteristics were similar in both arms (n = 29 each). Median knowledge score for Biostatistics increased from a baseline of 49% to 64% (p < 0.001) 3 months after the on-site course, and from 48% to 63% (p = 0.009) after the on-line course. For the on-site Research Ethics course, median score increased from 69% to 83% (p = 0.005), and for the on-line Research Ethics course from 62% to 80% (p < 0.001). Three months after the course, median gains in knowledge scores remained similar for the on-site and on-line platforms for both Biostatistics (16% vs. 12%; p = 0.59) and Research Ethics (17% vs. 13%; p = 0.14). Conclusion On-line and on-site training formats led to marked and similar improvements of knowledge in Biostatistics and Research Ethics. This, combined with logistical and cost advantages of on-line training, may make on-line courses particularly useful for expanding health research capacity in resource-limited settings.

We studied the effect of several compounds that influence different cell activation steps on platelet-activating factor (PAF)-induced basophil histamine secretion. Isobutylmethylxanthine (1-100 microM), dimaprit (1-100 microM) and dibutyryl adenosine 3',5'-cyclic phosphate (cAMP; 0.01-1 mM), that increase intracellular cAMP levels, concentration-dependently inhibited PAF-elicited histamine release. Rolipram (phosphodiesterase, PDE, isotype IV inhibitor; 0.1 nM-10 microM) potently inhibited histamine secretion activated by PAF, whereas SKF95654 (PDE III inhibitor; 0.01-10 microM) was ineffective. The kinase inhibitor, staurosporine (0.1-100 nM), enhanced PAF-induced basophil histamine release, whereas the G-protein inhibitor, pertussis toxin (1 microgram/ml), had an inhibitory effect. The specific lipoxygenase inhibitor, AA-861 (0.1-10 microM), inhibited PAF-activated histamine release, while the leukotriene A4 hydrolase inhibitor, bestatin (100 microM), had only a marginal effect. Finally, the Ca2+ channel entry blockers, verapamil (3-30 microM) and zinc (1.5-50 microM), inhibited PAF-induced histamine release. These results suggest that PAF is a unique secretagogue for human basophils unlike antigen, anti-IgE or univalent stimuli.

The effects of a putatively specific 5-lipoxygenase inhibitor, 2(12-hydroxydodeca-5,10-dinyl)-3,5,6-trimethyl-1,4-benzoquin one (AA-861), and its major metabolite, M-I, were assessed using anti-IgE activated human basophils, lung mast cells and skin mast cells. In basophils and lung mast cells, no effects on histamine release were observed, whereas leukotriene C4 (LTC4) production was inhibited (IC50 values less than 1 microM). In addition, prostaglandin D2 (PGD2) production was inhibited in lung mast cells (IC50 congruent to 5 microM). In contrast, in skin mast cells both histamine release and PGD2 production were reduced by AA-861 and M-I, with IC50 values of congruent to 5 and 0.4 microM for histamine and PGD2, respectively. These data reveal biochemical heterogeneity among human histamine-containing cells and underscore the necessity of assessing a pharmacologic agonist in relevant cell systems.