Outcomes of HIV treatment from the private sector in low-income and middle-income countries: a systematic review protocol

Introduction: Private sector provision of HIV treatment is increasing in low-income and middle-income countries (LMIC). However, there is limited documentation of its outcomes. This protocol reports a proposed systematic review that will synthesise clinical outcomes of private sector HIV treatment in LMIC. Methods and analysis: This review will be conducted in accordance with the preferred reporting items for systematic review and meta-analyses protocols. Primary outcomes will include: (1) proportion of eligible patients initiating antiretroviral therapy (ART); (2) proportion of those on ART with 90% ART adherence (based on any measure reported); (3) proportion screened for non-communicable diseases (specifically cervical cancer, diabetes, hypertension and mental ill health); (iv) proportion screened for tuberculosis. A search of five electronic bibliographical databases (Embase, Medline, PsychINFO, Web of Science and CINAHL) and reference lists of included articles will be conducted to identify relevant articles reporting HIV clinical outcomes. Searches will be limited to LMIC. No age, publication date, study-design or language limits will be applied. Authors of relevant studies will be contacted for clarification. Two reviewers will independently screen citations and abstracts, identify full text articles for inclusion, extract data and appraise the quality and bias of included studies. Outcome data will be pooled to generate aggregative proportions of primary and secondary outcomes. Descriptive statistics and a narrative synthesis will be presented. Heterogeneity and sensitivity assessments will be conducted to aid interpretation of results. Ethics and dissemination: The results of this review will be disseminated through a peer-reviewed scientific manuscript and at international scientific conferences. Results will inform quality improvement strategies, replication of identified good practices, potential policy changes, and future research

STICKING OUT AND FITTING IN: EXPERIENCES OF BLACK AND ASIAN PACIFIC ISLANDER DESI AMERICAN STUDENTS AT SCRIPPS COLLEGE

There is a lack of research about the experiences of students of color at predominantly white women’s colleges. Women’s colleges are institutions that have evolved over hundreds of years to support the education of marginalized genders, including transgender women and nonbinary people in recent years. Many women’s colleges have a white majority of students, which can have adverse effects on students of color pursuing their education. Collecting data from Scripps College, a women’s college with 40% students of color, 12 interviews were conducted with students who self-identified as Black or Asian American. Results found that students of color who experience alienation from the institution and their peers form their own community networks to uplift one another

Characterisation of the plasmodium falciparum HSP70-HSP90 organising protein

A Thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy in the Department of Biochemistry and Microbiology at the University of Zululand, South Africa, 2014.Malaria is caused by Plasmodium falciparum (P. falciparum) parasite and accounts for approximately more than half a million deaths yearly. P. falciparum survives under various physiological conditions during its life cycle. The parasite employs its molecular chaperones machinery particularly heat shock proteins (Hsps) to protect its protein constituents. This enables it to circumvent the effects of the stress linked to its life cycle. P. falciparum Hsp70-1 (PfHsp70-1; PF3D7_0818900) and P. falciparum Hsp90 (PfHsp90; PF3D7_0708400) are some of the major Hsps involved in the cytoprotection of the parasite and therefore pathogenesis of malaria. Hsp70 and Hsp90 are brought into close proximity by Hsp70-Hsp90 organising protein (Hop), allowing Hsp70 to pass partially folded substrates such as kinases to Hsp90 for further folding. Although a Hop homologue in P. falciparum (PfHop; PF3D7_1434300) is represented on the parasite genome, it is yet to be characterised. The objective of the study was to characterise the role of PfHop in mediating the functional partnership between PfHsp70-1 and PfHsp90. Structural domains and motifs such as the tetratricopeptide repeat (TPR) that are conserved across Hop homologues were identified in the PfHop. Data suggested that PfHop is a canonical Hop homologue of the P. falciparum. Recombinant PfHop was heterologously expressed in Escherichia coli (E. coli) XL1 Blue cells and subsequently purified using nickel-chelating Sepharose beads. Using surface plasmon resonance spectroscopy (SPR) analysis, recombinant PfHop was shown to bind to PfHsp70-1 in a concentration dependent manner. Based on immunofluorescence assay (IFA), it was demonstrated that PfHop is predominantly cytosolic and it tended to co-localise with PfHsp70-1 and PfHsp90. Co-immunoprecipitation studies suggested that PfHop and PfHsp70-1 interact. It was also demonstrated that PfHop was concominantly upregulated with PfHsp70-1 during the intraerythrocytic cycle. These findings suggest possible cytoprotective roles of PfHop and PfHsp70-1 during parasite host invasion and development in the erythrocyte. In conclusion, the study provides evidence that PfHop mediates the function of PfHsp70-1 and in particular its functional interaction with PfHsp90

Awareness and Willingness to Use HIV Pre-Exposure Prophylaxis among Men Who Have Sex with Men in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis

Introduction: To facilitate provision of pre-exposure prophylaxis (PrEP) in low- and middle-income countries (LMIC), a better understanding of potential demand and user preferences is required. This review assessed awareness and willingness to use oral PrEP among men who have sex with men (MSM) in LMIC. Methods: Electronic literature search of Cochrane library, Embase, PubMed, PsychINFO, CINHAL, Web of Science, and Google Scholar was conducted between July and September 2016. Reference lists of relevant studies were searched, and three authors contacted for additional data. Non-peer reviewed publications were excluded. Studies were screened for inclusion, and relevant data abstracted, assessed for bias, and synthesized. Results: In total, 2186 records were identified, of which 23 studies involving 14,040 MSM from LMIC were included. The proportion of MSM who were aware of PrEP was low at 29.7% (95% CI: 16.9-44.3). However, the proportion willing to use PrEP was higher, at 64.4% (95% CI: 53.3-74.8). Proportions of MSM aware of PrEP was Conclusions: This review found that despite low levels of awareness of PrEP, MSM in LMIC are willing to use it if they are supported appropriately to deal with a range of individual, social, and structural barriers

In silico exploration of Lycoris alkaloids as potential inhibitors of SARS-CoV-2 main protease (Mpro)

Coronavirus disease 2019 (COVID-19) is a pandemic whose adverse effects have been felt all over the world. As of August 2022, reports indicated that over 500 million people in the world had been infected and the number of rising deaths from the disease were slightly above 6.4 million. New variants of the causative agent, SARS-CoV-2 are emanating now and then and some are more efficacious and harder to manage. SARS-CoV-2 main protease (Mpro) has essential functions in viral gene expression and replication through proteolytic cleavage of polyproteins. Search for SARS-CoV-2 Mpro inhibitors is a vital step in the treatment and management of COVID-19. In this study, we investigated whether alkaloids with antiviral and myriad other bioactivities from the genus Lycoris can act as SARS-CoV-2 Mpro inhibitors. We conducted a computer-aided drug design study through screening optimal ligands for SARS-CoV-2 Mpro from a list of over 150 Lycoris alkaloids created from online databases such as ChEMBL, PubChem, ChemSpider, and published journal papers. The In silico study involved molecular docking of Lycoris alkaloids to SARS-CoV-2 Mpro active site, absorption, distribution, metabolism, elimination and toxicity (ADMET) screening and finally molecular dynamic (MD) simulations of the most promising ligand-SARS-CoV-2 Mpro complexes. The study identified 3,11-dimethoxy-lycoramine, narwedine, O-demethyllycoramine and epilycoramine as drug-like and lead-like Lycoris alkaloids with favorable ADMET properties and are very likely to have an inhibition activity on SARS-CoV-2 Mpro and may become potential drug candidates. DOI: http://dx.doi.org/10.5281/zenodo.704180

World Antimalarial Resistance Network (WARN) IV: Clinical pharmacology

A World Antimalarial Resistance Network (WARN) database has the potential to improve the treatment of malaria, through informing current drug selection and use and providing a prompt warning of when treatment policies need changing. This manuscript outlines the contribution and structure of the clinical pharmacology component of this database. The determinants of treatment response are multi-factorial, but clearly providing adequate blood concentrations is pivotal to curing malaria. The ability of available antimalarial pharmacokinetic data to inform optimal dosing is constrained by the small number of patients studied, with even fewer (if any) studies conducted in the most vulnerable populations. There are even less data relating blood concentration data to the therapeutic response (pharmacodynamics). By pooling all available pharmacokinetic data, while paying careful attention to the analytical methodologies used, the limitations of small (and thus underpowered) individual studies may be overcome and factors that contribute to inter-individual variability in pharmacokinetic parameters defined. Key variables for pharmacokinetic studies are defined in terms of patient (or study subject) characteristics, the formulation and route of administration of the antimalarial studied, the sampling and assay methodology, and the approach taken to data analysis. Better defining these information needs and criteria of acceptability of pharmacokinetic-pharmacodynamic (PK-PD) studies should contribute to improving the quantity, relevance and quality of these studies. A better understanding of the pharmacokinetic properties of antimalarials and a more clear definition of what constitutes "therapeutic drug levels" would allow more precise use of the term "antimalarial resistance", as it would indicate when treatment failure is not caused by intrinsic parasite resistance but is instead the result of inadequate drug levels. The clinical pharmacology component of the WARN database can play a pivotal role in monitoring accurately for true antimalarial drug resistance and promptly correcting sub-optimal dosage regimens to prevent these contributing to the emergence and spread of antimalarial resistance.Bill and Melinda Gates Foundation

Resisting and challenging stigma in Uganda: the role of support groups of people living with HIV.

INTRODUCTION: Global scale up of antiretroviral therapy is changing the context of HIV-related stigma. However, stigma remains an ongoing concern in many countries. Groups of people living with HIV can contribute to the reduction of stigma. However, the pathways through which they do so are not well understood. METHODS: This paper utilizes data from a qualitative study exploring the impact of networked groups of people living with HIV in Jinja and Mbale districts of Uganda. Participants were people living with HIV (n=40), members of their households (n=10) and their health service providers (n=15). Data were collected via interviews and focus group discussions in 2010, and analyzed inductively to extract key themes related to the approaches and outcomes of the groups' anti-stigma activities. RESULTS: Study participants reported that HIV stigma in their communities had declined as a result of the collective activities of groups of people living with HIV. However, they believed that stigma remained an ongoing challenge. Gender, family relationships, social and economic factors emerged as important drivers of stigma. Challenging stigma collectively transcended individual experiences and united people living with HIV in a process of social renegotiation to achieve change. Groups of people living with HIV provided peer support and improved the confidence of their members, which ultimately reduced self-stigma and improved their ability to deal with external stigma when it was encountered. CONCLUSIONS: Antiretroviral therapy and group-based approaches in the delivery of HIV services are opening up new avenues for the collective participation of people living with HIV to challenge HIV stigma and act as agents of social change. Interventions for reducing HIV stigma should be expanded beyond those that aim to increase the resilience and coping mechanisms of individuals, to those that build the capacity of groups to collectively cope with and challenge HIV stigma. Such interventions should be gender sensitive and should respond to contextual social, economic and structural factors that drive stigma

Role and outcomes of community health workers in HIV care in sub-Saharan Africa: a systematic review.

INTRODUCTION: The provision of HIV treatment and care in sub-Saharan Africa faces multiple challenges, including weak health systems and attrition of trained health workers. One potential response to overcome these challenges has been to engage community health workers (CHWs). METHODOLOGY: A systematic literature search for quantitative and qualitative studies describing the role and outcomes of CHWs in HIV care between inception and December 2012 in sub-Saharan Africa was performed in the following databases: PubMed, PsychINFO, Embase, Web of Science, JSTOR, WHOLIS, Google Scholar and SAGE journals online. Bibliographies of included articles were also searched. A narrative synthesis approach was used to analyze common emerging themes on the role and outcomes of CHWs in HIV care in sub-Saharan Africa. RESULTS: In total, 21 studies met the inclusion criteria, documenting a range of tasks performed by CHWs. These included patient support (counselling, home-based care, education, adherence support and livelihood support) and health service support (screening, referral and health service organization and surveillance). CHWs were reported to enhance the reach, uptake and quality of HIV services, as well as the dignity, quality of life and retention in care of people living with HIV. The presence of CHWs in clinics was reported to reduce waiting times, streamline patient flow and reduce the workload of health workers. Clinical outcomes appeared not to be compromised, with no differences in virologic failure and mortality comparing patients under community-based and those under facility-based care. Despite these benefits, CHWs faced challenges related to lack of recognition, remuneration and involvement in decision making. CONCLUSIONS: CHWs can clearly contribute to HIV services delivery and strengthen human resource capacity in sub-Saharan Africa. For their contribution to be sustained, CHWs need to be recognized, remunerated and integrated in wider health systems. Further research focusing on comparative costs of CHW interventions and successful models for mainstreaming CHWs into wider health systems is needed