Failure of scabies treatment: a systematic review and meta-analysis.

BACKGROUND: Treatment failure is considered to be an important factor in relation to the increase in scabies incidence over the last decade. However, the regional and temporal differences, in addition to the predictors of therapy failure, are unclear. OBJECTIVES: We aimed to conduct a systematic review of the prevalence of treatment failure in patients with scabies and investigation of associated factors. METHODS: We searched MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, Global Health and the Cochrane Central Register of Controlled Trials from inception to August 2021 for randomized and quasi-randomized trials, in addition to observational studies that enrolled children or adults diagnosed with confirmed or clinical scabies treated with permethrin, ivermectin, crotamiton, benzyl benzoate, malathion, sulfur or lindane, and measured treatment failure or factors associated with treatment failure. We performed a random effects meta-analysis for all outcomes reported by at least two studies. RESULTS: A total of 147 studies were eligible for inclusion in the systematic review. The overall prevalence of treatment failure was 15.2% [95% confidence interval (CI) 12.9-17.6; I2 = 95.3%, moderate-certainty evidence] with regional differences between World Health Organization regions (P = 0.003) being highest in the Western Pacific region (26.9%, 95% CI 14.5-41.2). Oral ivermectin (11.8%, 95% CI 8.4-15.4), topical ivermectin (9.3%, 95% CI 5.1-14.3) and permethrin (10.8%, 95% CI 7.5-14.5) had relatively lower failure prevalence compared with the overall prevalence. Failure prevalence was lower in patients treated with two doses of oral ivermectin (7.1%, 95% CI 3.1-12.3) compared with those treated with one dose (15.2%, 95% CI 10.8-20.2; P = 0.021). Overall and permethrin treatment failure prevalence in the included studies (1983-2021) increased by 0.27% and 0.58% per year, respectively. Only three studies conducted a multivariable risk factor analysis; no studies assessed resistance. CONCLUSIONS: A second dose of ivermectin showed lower failure prevalence than single-dose ivermectin, which should be considered in all guidelines. The increase in treatment failure over time hints at decreasing mite susceptibility for several drugs, but reasons for failure are rarely assessed. Ideally, scabicide susceptibility testing should be implemented in future studies.

COVID-19 pandemic stressors, familial discord, and anxiety among adolescents living with HIV in South Africa: pathways to non-adherence.

Adolescents living with HIV (ALHIV) have poorer adherence to antiretroviral treatment (ART). This study investigates the interconnectivity of stressors induced by the COVID-19 pandemic, anxiety and family dynamics on adolescents' adherence to ART. A telephone survey was conducted among 196 South African ALHIV previously enrolled in support groups. Generalized structural equations modeling was used to understand how pandemic-related stressors affected ART adherence. Respondents reported experiencing life stressors since the implementation of COVID-19 restrictions, including doing worse at school (32%), loss of household income (44%) and less food available (38%). Forty-two percent reported greater verbal aggression from adults at home and 60% experienced anxiety. The structural equations model demonstrated a direct path from experiencing life stressors to increased verbal aggression from caregivers, which led to anxiety and ultimately, poorer ART adherence. Each stressor experienced increased the odds of experiencing verbal aggression by 51% (OR=1.51, 95%CI=1.14-2.00) which, in turn, increased the odds of having anxiety four-fold (OR=4.1, 95%C =2.16-7.76). Anxiety was associated with a 74% reduction in the odds of being fully ART adherent (OR=0.26, 95%CI=0.08-0.81). COVID-19-induced stressors exacerbated the mental and physical vulnerability of ALHIV. Findings elucidate how both discord at home and anxiety can result in poorer ART adherence.

Latent class analysis of ART barriers among adolescents and young adults living with HIV in South Africa.

This study examined adherence to antiretroviral therapy (ART) among adolescents and young adults living with HIV in South Africa. Using survey data from 857 youth on ART, the study employed latent class analysis to identify subgroups based on self-reported reasons for missed ART doses. Three distinct classes emerged: the largest class (85%) occasionally forgot to take their medication or missed a dose because others were around, the second class (9%) missed doses only due to feeling sick, and the third class (6%) faced multiple barriers such as forgetting, feeling sick, worrying about side effects, or doubting the effectiveness of ART. Youth who reported multiple barriers to adherence had significantly lower adjusted odds (AOR = 0.35, 95% CI = 0.16-0.78) of reporting 90% past month adherence compared to those who occasionally forgot their medication. Additionally, contextual factors such as food security, being treated well at the clinic, and being accompanied to the clinic were associated with higher odds of adherence. The findings highlight the importance of considering co-occurring barriers to adherence and tailoring interventions accordingly. Addressing contextual factors, such as ensuring food security and providing supportive clinic environments, is also crucial for promoting optimal adherence among adolescents and young adults living with HIV.

The Cameroon Health Research and Evidence Database (CAMHRED): tools and methods for local evidence mapping.

BACKGROUND: Local evidence is important for contextualized knowledge translation. It can be used to adapt global recommendations, to identify future research priorities and inform local policy decisions. However, there are challenges in identifying local evidence in a systematic, comprehensive, and timely manner. There is limited guidance on how to map local evidence and provide it to users in an accessible and user-friendly way. In this study, we address these issues by describing the methods for the development of a centralized database of health research evidence for Cameroon and its applications for research prioritization and decision making. METHODS: We searched 10 electronic health databases and hand-searched the archives of non-indexed African and Cameroonian journals. We screened titles, abstracts, and full texts of peer reviewed journal articles published between 1999 and 2019 in English or French that assess health related outcomes in Cameroonian populations. We extracted relevant study characteristics based on a pre-established guide. We developed a coding scheme or taxonomy of content areas so that local evidence is mapped to corresponding domains and subdomains. Pairs of reviewers coded articles independently and resolved discrepancies by consensus. Moreover, we developed guidance on how to search the database, use search results to create evidence maps and conduct knowledge gap analyses. RESULTS: The Cameroon Health Research and Evidence Database (CAMHRED) is a bilingual centralized online portal of local evidence on health in Cameroon from 1999 onwards. It currently includes 4384 studies categorized into content domains and study characteristics (design, setting, year and language of publication). The database is searchable by keywords or through a guided search. Results including abstracts, relevant study characteristics and bibliographic information are available for users to download. Upon request, guidance on how to optimize search results for applications like evidence maps and knowledge gap analyses is also available. CONCLUSIONS: CAMHRED ( https://camhred.org/ ) is a systematic, comprehensive, and centralized resource for local evidence about health in Cameroon. It is freely available to stakeholders and provides an additional resource to support their work at various levels in the research process.

A collaborative care package for depression comorbid with chronic physical conditions in South Africa.

INTRODUCTION: A task-sharing collaborative care model for integrated depression care for South Africa's burgeoning primary health care population with chronic conditions was developed and tested through two pragmatic cluster randomized controlled trials. One trial focused on patients with hypertension and was located in one district where a collaborative care model was co-designed with district stakeholders. The other trial, focused on patients on antiretroviral treatment, was located in the same district site, with the addition of a second neighbouring district, without adaptation of the original model. This paper describes the package used to implement this model, and implementation outcomes across the two sites, and summarises lessons and challenges. METHODS: The Template for Intervention Description and Replication (TIDieR) framework, adapted for complex health systems interventions, was used to describe components of the package. Additional elements of 'modifications made' and 'actual implementation' introduced in the 'Getting messier with TIDieR' framework, were used to describe implementation outcomes in terms of reach, adoption and implementation across the two trial districts. RESULTS: In the absence of a co-design process to adapt the model to the context of the second site, there was less system level support for the model. Consequently, more project employed human resources were deployed to support training of primary care nurses in identification and referral of patients with depression; and supervise co-located lay counsellors. Referrals to co-located lay counselling services were more than double in the second site. However, uptake of counselling sessions was greater in the first site. This was attributed to greater in-vivo supervision and support from existing mental health specialists in the system. There was greater reliance on online supervision and support in the second site where geographical distances between clinics were larger. CONCLUSION: The need for in-country co-designed collaborative care models, and 'implementation heavy' implementation research to understand adaptations required to accommodate varying in-country health system contexts is highlighted.

Guidelines are needed for studies of pre-treatment HIV drug resistance: a methodological study.

BACKGROUND: The expansion of access to antiretroviral therapy (ART) has been accompanied by an increase in pre-treatment drug resistance (PDR). While it is critical to monitor the increasing prevalence of PDR across countries and populations to inform optimal regimen selection, the completeness of reporting is often suboptimal, limiting the interpretation and generalizability of the results. Indeed, there is no formal guidance on how studies investigating the prevalence of drug resistance should be reported. Thus, we sought to determine the completeness of reporting in studies of PDR and the factors associated with sub-optimal reporting to ascertain the need for guidelines. METHODS: As part of a systematic review on the global prevalence of PDR in key populations (men who have sex with men, sex workers, transgender people, people who inject drugs and people in prisons), we searched 10 electronic databases until January 2019. We extracted information on selected study characteristics useful for interpreting prevalence data. Data were extracted in duplicate. Analyses of variance and correlation were used to explore factors that may explain the number of items reported. RESULTS: We found 650 studies of which 387 were screened as full text and 234 were deemed eligible. The included studies were published between 1997 and 2019 and included a median of 239 (quartile 1 = 101; quartile 3 = 778) participants. Most studies originated from high-income countries (125/234; 53.0%). Of 23 relevant data items, including study design, setting, participant sociodemographic characteristics, HIV risk factors, type of resistance test conducted, definition of resistance, the mean (standard deviation) number of items reported was 13 (2.2). We found that more items were reported in studies published more recently (r = 0.20; p < 0.002) and in studies at low risk of bias (F [2231] = 8.142; p < 0.001). CONCLUSIONS: Incomplete reporting in studies on PDR makes characterising levels of PDR in subpopulations across countries challenging. Hence, guidelines are needed to define a minimum set of variables to be included in such studies.

Nurse led home-based care for people with HIV/AIDS.

BACKGROUND: Home-based care is used in many countries to increase quality of life and limit hospital stay, particularly where public health services are overburdened. Home-based care objectives for HIV/AIDS can include medical care, delivery of antiretroviral treatment and psychosocial support. This review assesses the effects of home-based nursing on morbidity in people infected with HIV/AIDS. METHODS: The trials studied are in HIV positive adults and children, regardless of sex or setting and all randomised controlled. Home-based care provided by qualified nurses was compared with hospital or health-facility based treatment. The following electronic databases were searched from January 1980 to March 2015: AIDSearch, CINAHL, Cochrane Register of Controlled Trials, EMBASE, MEDLINE and PsycINFO/LIT, with an updated search in November 2016. Two authors independently screened titles and abstracts from the electronic search based on the study design, interventions and types of participant. For all selected abstracts, full text articles were obtained. The final study selection was determined with use of an eligibility form. Data extraction was performed independently from assessment of risk of bias. The results were analysed by narrative synthesis, in order to be able to obtain relevant effect measures plus 95% confidence intervals. RESULTS: Seven studies met the inclusion criteria. The trial size varied from 37 to 238 participants. Only one trial was conducted in children. Five studies were conducted in the USA and two in China. Four studies looked at home-based adherence support and the rest at providing home-based psychosocial support. Reported adherence to antiretroviral drugs improved with nurse-led home-based care but did not affect viral load. Psychiatric nurse support in those with existing mental health conditions improved mental health and depressive symptoms. Home-based psychological support impacted on HIV stigma, worry and physical functioning and in certain cases depressive symptoms. CONCLUSIONS: Nurse-led home-based interventions could help adherence to antiretroviral therapy and improve mental health. Further larger scale studies are needed, looking in more detail at improving medical care for HIV, especially related to screening and management of opportunistic infections and co-morbidities.

Artemisinin-naphthoquine for treating uncomplicated Plasmodium falciparum malaria.

BACKGROUND: The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) for treating people with Plasmodium falciparum malaria. Five combinations are currently recommended, all administered over three days. Artemisinin-naphthoquine is a new combination developed in China, which is being marketed as a one-day treatment. Although shorter treatment courses may improve adherence, the WHO recommends at least three days of the short-acting artemisinin component to eliminate 90% P. falciparum parasites in the bloodstream, before leaving the longer-acting partner drug to clear the remaining parasites. OBJECTIVES: To evaluate the efficacy and safety of the artemisinin-naphthoquine combination for treating adults and children with uncomplicated P. falciparum malaria. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE; and LILACS up to January 2015. We also searched the metaRegister of Controlled Trials (mRCT) using 'malaria' and 'arte* OR dihydroarte*' as search terms. SELECTION CRITERIA: Randomized controlled trials comparing artemisinin-naphthoquine combinations with established WHO-recommended ACTs for the treatment of adults and children with uncomplicated malaria due to P. falciparum. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy' and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on gametocytes, haemoglobin, and adverse events. We assessed the quality of evidence using the GRADE approach. MAIN RESULTS: Four trials, enrolling 740 adults and children, met the inclusion criteria. Artemisinin-naphthoquine was administered as a single dose (two trials), as two doses given eight hours apart (one trial), and once daily for three days (one trial), and compared to three-day regimens of established ACTs. Three additional small pharmaceutical company trials have been carried out. We have requested the data but have not received a response from the company. Artemisinin-naphthoquine versus artemether-lumefantrineIn three small trials from Benin, Côte d'Ivoire, and Papua New Guinea, both combinations had a very low incidence of treatment failure at Day 28, and there were no differences demonstrated in PCR-unadjusted, or PCR-adjusted treatment failure (three trials, 487 participants, low quality evidence). Only the single study from Papua New Guinea followed participants up to Day 42, and the number of treatment failures remained very low with both combinations (one trial, 186 participants, very low quality evidence). Artemisinin-naphthoquine versus dihydroartemisinin-piperaquineIn a single small trial from Indonesia, treatment failure at Day 28 and Day 42 was very low in both groups with no differences demonstrated (one trial, 144 participants, very low quality evidence). AUTHORS' CONCLUSIONS: The results of these few trials of artemisinin-naphthoquine are promising, but further trials from multiple settings are required to reliably demonstrate the relative efficacy and safety compared to established ACTs. Future trials should be adequately powered to demonstrate non-inferiority, and regimens incorporating three days of the artemisinin component are probably preferable to the one-day regimens.

Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum malaria.

BACKGROUND: The World Health Organization (WHO) recommends Artemisinin-based Combination Therapy (ACT) for treating uncomplicated Plasmodium falciparum malaria. This review aims to assist the decision-making of malaria control programmes by providing an overview of the relative effects of dihydroartemisinin-piperaquine (DHA-P) versus other recommended ACTs. OBJECTIVES: To evaluate the effectiveness and safety of DHA-P compared to other ACTs for treating uncomplicated P. falciparum malaria in adults and children. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE; LILACS, and the metaRegister of Controlled Trials (mRCT) up to July 2013. SELECTION CRITERIA: Randomized controlled trials comparing a three-day course of DHA-P to a three-day course of an alternative WHO recommended ACT in uncomplicated P. falciparum malaria. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy' and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on gametocytes, haemoglobin, and adverse events. We assessed the quality of evidence using the GRADE approach. MAIN RESULTS: We included 27 trials, enrolling 16,382 adults and children, and conducted between 2002 and 2010. Most trials excluded infants aged less than six months and pregnant women. DHA-P versus artemether-lumefantrineIn Africa, over 28 days follow-up, DHA-P is superior to artemether-lumefantrine at preventing further parasitaemia (PCR-unadjusted treatment failure: RR 0.34, 95% CI 0.30 to 0.39, nine trials, 6200 participants, high quality evidence), and although PCR-adjusted treatment failure was below 5% for both ACTs, it was consistently lower with DHA-P (PCR-adjusted treatment failure: RR 0.42, 95% CI 0.29 to 0.62, nine trials, 5417 participants, high quality evidence). DHA-P has a longer prophylactic effect on new infections which may last for up to 63 days (PCR-unadjusted treatment failure: RR 0.71, 95% CI 0.65 to 0.78, two trials, 3200 participants, high quality evidence).In Asia and Oceania, no differences have been shown at day 28 (four trials, 1143 participants, moderate quality evidence), or day 63 (one trial, 323 participants, low quality evidence).Compared to artemether-lumefantrine, no difference was seen in prolonged QTc (low quality evidence), and no cardiac arrhythmias were reported. The frequency of other adverse events is probably similar with both combinations (moderate quality evidence). DHA-P versus artesunate plus mefloquineIn Asia, over 28 days follow-up, DHA-P is as effective as artesunate plus mefloquine at preventing further parasitaemia (PCR-unadjusted treatment failure: eight trials, 3487 participants, high quality evidence). Once adjusted by PCR to exclude new infections, treatment failure at day 28 was below 5% for both ACTs in all eight trials, but lower with DHA-P in two trials (PCR-adjusted treatment failure: RR 0.41 95% CI 0.21 to 0.80, eight trials, 3482 participants, high quality evidence). Both combinations contain partner drugs with very long half-lives and no consistent benefit in preventing new infections has been seen over 63 days follow-up (PCR-unadjusted treatment failure: five trials, 2715 participants, moderate quality evidence).In the only trial from South America, there were fewer recurrent parastaemias over 63 days with artesunate plus mefloquine (PCR-unadjusted treatment failure: RR 6.19, 95% CI 1.40 to 27.35, one trial, 445 participants, low quality evidence), but no differences were seen once adjusted for new infections (PCR-adjusted treatment failure: one trial, 435 participants, low quality evidence).DHA-P is associated with less nausea, vomiting, dizziness, sleeplessness, and palpitations compared to artesunate plus mefloquine (moderate quality evidence). DHA-P was associated with more frequent prolongation of the QTc interval (low quality evidence), but no cardiac arrhythmias were reported. AUTHORS' CONCLUSIONS: In Africa, dihydroartemisinin-piperaquine reduces overall treatment failure compared to artemether-lumefantrine, although both drugs have PCR-adjusted failure rates of less than 5%. In Asia, dihydroartemisinin-piperaquine is as effective as artesunate plus mefloquine, and is better tolerated.

Challenges and opportunities for implementation and dissemination of a task- sharing counselling intervention for depression at primary health care level in South Africa.

BACKGROUND: The treatment gap for mental health services is a growing public health concern. A lay-counselling service located at primary health care (PHC) level could potentially help to close the large treatment gap for common mental disorders in South Africa. The aim of this study was to understand multilevel factors contributing to implementation and potential dissemination of such a service for depression at PHC level. METHODS: Process qualitative data of the lay-counselling service for patients with depressive symptoms was collected alongside a pragmatic randomized controlled trial evaluating a collaborative care model that included a lay-counselling service for patients with depressive symptoms. Semi-structured key informant interviews (SSI) were conducted with a purposive sample of PHC providers (lay-counsellors, nurse practitioners, operational managers), lay-counsellor supervisors, district and provincial managers, and patients in receipt of services. A total of 86 interviews were conducted. The Consolidated Framework for Implementation Research (CFIR) was used to guide data collection as well as Framework Analysis to determine barriers and facilitators for implementation and dissemination of the lay-counselling service. RESULTS: Facilitators identified include supervision and support available for counsellors; person focused counselling approach; organizational integration of the counsellor within facilities. Barriers included lack of organizational support of the counselling service, including lack of counselling dedicated space; high counsellor turnover, resulting in a counsellor not available all the time; lack of an identified cadre to deliver the intervention in the system; and treatment of mental health conditions including counselling not included within mental health indicators. CONCLUSIONS: Several system level issues need to be addressed to promote integration and dissemination of lay-counselling services within PHC facilities in South Africa. Key system requirements are facility organizational readiness for improvement of integration of lay-counselling services; formal recognition of counselling services provided by lay counsellors as well as inclusion of lay counselling as a treatment modality within mental health treatment data element definitions and the need for diversification of the roles of psychologists to include training and supervision of lay counsellors was also emphasized.

Describing Engagement in the HIV Care Cascade: A Methodological Study.

Introduction: Engagement in the HIV care cascade is required for people living with HIV (PLWH) to achieve an undetectable viral load. However, varying definitions of engagement exist, contributing to heterogeneity in research regarding how many individuals are actively participating and benefitting from care. A standardized definition is needed to enhance comparability and pooling of data from engagement studies. Objectives: The objective of this paper was to describe the various definitions for engagement used in HIV clinical trials. Methods: Articles were retrieved from CASCADE, a database of 298 clinical trials conducted to improve the HIV care cascade (https://hivcarecascade.com/), curated by income level, vulnerable population, who delivered the intervention, the setting in which it was delivered, the intervention type, and the level of pragmatism of the intervention. Studies with engagement listed as an outcome were selected from this database. Results: 13 studies were eligible, of which five did not provide an explicit definition for engagement. The remaining studies used one or more of the following: appointment adherence (n=6), laboratory testing (n=2), adherence to antiretroviral therapy (n=2), time specification (n=5), intervention adherence (n=5), and quality of interaction (n=1). Conclusion: This paper highlights the existing diversity in definitions for engagement in the HIV care cascade and categorize these definitions into appointment adherence, laboratory testing, adherence to antiretroviral therapy, time specification, intervention adherence, and quality of interaction. We recommend consensus on how to describe and measure engagement.

Service delivery models that promote linkages to PrEP for adolescent girls and young women and men in sub-Saharan Africa: a scoping review.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is an emerging biomedical prevention intervention. Documenting PrEP service delivery models (SDMs) that promote linkage to and continuation of PrEP will inform guidelines and maximise roll-out. OBJECTIVES: To synthesise and appraise the effectiveness and feasibility of PrEP SDMs designed to promote linkage to PrEP care among adolescent girls and young women (AGYW) and men in sub-Saharan Africa (SSA). ELIGIBILITY CRITERIA: Primary quantitative and qualitative studies published in English and conducted in SSA were included. No restrictions on the date of publication were applied. SOURCES OF EVIDENCE: Methodology outlined in the Joanna Briggs Institute reviewers' manual was followed. PubMed, Cochrane library, Scopus, Web of Science and online-conference abstract archives were searched. CHARTING METHODS: Data on article, population, intervention characteristics and key outcomes was charted in REDCap. RESULTS AND CONCLUSION: Of the 1204 identified records, 37 (met the inclusion criteria. Health facility-based integrated models of PrEP delivery with family planning, maternal and child health or sexual and reproductive services to AGYW resulted in PrEP initiation of 16%-90%. Community-based drop-in centres (66%) was the preferred PrEP outlet for AGYW compared with public clinics (25%) and private clinics (9%). Most men preferred community-based delivery models. Among individuals who initiated PrEP, 50% were men, 62% were <35 years old and 97% were tested at health fairs compared with home testing. Integrated antiretroviral therapy (ART)-PrEP delivery was favoured among serodiscordant couples with 82.9% of couples using PrEP or ART with no HIV seroconversions. PrEP initiation within healthcare facilities was increased by perceived client-friendly services and non-judgemental healthcare workers. Barriers to PrEP initiation included distance to travel to and time spent at health facilities and perceived community stigma. PrEP SDMs for AGYW and men need to be tailored to the needs and preferences for each group. Programme implementers should promote community-based SDMs to increase PrEP initiation among AGYW and men.

Measures of Retention in HIV Care: A Study Within a Review.

People living with HIV (PLHIV) need lifelong medical care. However, retention in HIV care is not measured uniformly, making it challenging to compare or pool data. The objective of this study within a review (SWAR) is to describe the assortment of definitions used for retention in HIV care in randomized controlled trials (RCTs). We conducted a SWAR, drawing data from an overview of systematic reviews on interventions to improve the HIV care cascade. Ethics review was not required for this analysis of secondary data. We identified RCTs of interventions used to improve retention in care for PLHIV, including all age groups and extracted the definitions used and their characteristics. We identified 50 trials that measured retention published between 2007 and 2021 and provided 59 definitions for retention in care. The definitions consisted of nine different characteristics with follow-up time (n = 47), and clinical visits (n = 36) most used. The definitions of retention in HIV care are highly heterogeneous. In this study, we present the pros and cons of characteristics used to measure retention in HIV care.

Service delivery models for enhancing linkage to and retention in HIV care services for adolescent girls and young women and adolescent boys and young men: a protocol for an overview of systematic reviews.

INTRODUCTION: Recent advances in the HIV care continuum have shown that an individual diagnosed with HIV should be initiated on antiretroviral therapy as soon as possible regardless of the CD4 count levels and retained in HIV care services. Studies have reported large losses in the HIV continuum of care, before and after the era of universal test and treat. Several systematic reviews have reported on the strategies for improving linkage to and retention in HIV treatment and care. The purpose of this overview of systematic reviews is to identify HIV care interventions or service delivery models (SDMs) and synthesise evidence on the effects of these to link adolescent girls and young women (AGYW) and adolescent boys and young men (ABYM) to care and retain them in care. We also aim to highlight gaps in the evidence on interventions and SDMs to improve linkage and retention in HIV care of AGYW and ABYM. METHODS AND ANALYSIS: An electronic search of four online databases: PubMed, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science will be performed to identify systematic reviews on the effects of linkage to and retention in HIV care interventions or SDMs for AGYW aged 15-24 years and ABYM aged 15-35 years. Our findings on the effects of interventions and SDMs will be interpreted considering the intervention and or SDMs' effectiveness by the time period, setting and population of interest. Two or more authors will independently screen articles for inclusion using a priori criteria. ETHICS AND DISSEMINATION: Ethics approval is not required for this study as only published secondary data will be used. Our findings will be disseminated through peer-reviewed publication, conference abstracts and through presentations to stakeholders and other community fora. The findings from this overview of systematic reviews will inform mixed-methods operations research on HIV intervention programming and delivery of HIV care services for AGYW and ABYM in South Africa. PROSPERO REGISTRATION NUMBER: CRD42020177933.

Virological measures and factors associated with outcomes, and missing outcome data in HIV clinical trials: a methodological study.

BACKGROUND: To evaluate the definition of HIV virological outcomes in the literature and factors associated with outcomes and missing outcome data. METHODS: We conducted a methodological review of HIV RCTs using a search (2009-2019) of PubMed, Embase and the Cochrane Central Register of Controlled Trials.Only full-text, peer-reviewed, randomised controlled trials (RCTs) that measured virological outcomes in people living with HIV, and published in English were included.We extracted study details and outcomes. We used logistic regression to identify factors associated with a viral threshold ≤50 copies/mL and linear regression to identify factors associated with missing outcome data. RESULTS: Our search yielded 5847 articles; 180 were included. A virological outcome was the primary outcome in 73.5% of studies. 89 studies (49.4%) used virological success. The remaining used change in viral load (VL) (33 studies, 18.3%); virological failure (59 studies, 32.8%); or virological rebound (9 studies, 5.0%). 96 studies (53.3%) set the threshold at ≤50 copies/mL; and 33.1% used multiple measures.Compared with government and privately funded studies, RCTs with industry funding (adjusted OR 6.39; 95% CI 2.15 to 19.00; p<0.01) were significantly associated with higher odds of using a VL threshold of ≤50 copies/mL. Publication year, intervention type, income level and number of patients were not associated with a threshold of ≤50 copies/mL. Trials with pharmacological interventions had less missing data (ß=-11.04; 95% CI -20.02 to -1.87; p=0.02). DISCUSSION: Country source of funding was associated with VL threshold choice and studies with pharmacological interventions had less missing data, which may in part explain heterogeneous virological outcomes across studies. Multiple measures of VL were not associated with missing data. The development of formal guidelines on virological outcome reporting in RCTs is needed.

Effectiveness of a task-sharing collaborative care model for identification and management of depressive symptoms in patients with hypertension attending public sector primary care clinics in South Africa: pragmatic parallel cluster randomised controlled trial.

BACKGROUND: We tested the real-world effectiveness of a collaborative task-sharing model on depressive symptom reduction in hypertensive Primary Health Care (PHC) patients in South Africa. METHOD: A pragmatic parallel cluster randomised trial in 20 clinics in the Dr Kenneth Kaunda district, North West province. PHC clinics were stratified by sub-district and randomised in a 1:1 ratio. Control clinics received care as usual (CAU), involving referral to PHC doctors and/or mental health specialists. Intervention clinics received CAU plus enhanced mental health training and a lay counselling referral service. Participant inclusion criteria were ≥ 18 years old, Patient Health Questionnaire-9 (PHQ-9) score ≥ 9 and receiving hypertension medication. Primary superiority outcome was ≥ 50% reduction in PHQ-9 score at 6 months. Statistical analyses comprised mixed effects regression models and a non-inferiority analysis. TRIAL REGISTRATION NUMBER: NCT02425124. RESULTS: Between April 2015 and October 2015, 1043 participants were enrolled (504 intervention and 539 control); 82% were women; half were ≥ 55 years. At 6 and 12 months follow-up, 91% and 89% of participants were interviewed respectively. One control group participant committed suicide. There was no significant difference in the primary outcome between intervention (N=256/456) and control (N=232/492) groups (55.9% versus 50.9%; adjusted risk difference = -0.04 ([95% CI = -0.19; 0.11], p = 0.6). The difference in PHQ-9 scores was within the defined equivalence limits at 6 and 12 months for the non-inferiority analysis. LIMITATIONS: The trial was limited by low exposure to depression treatment by trial participants and by observed co-intervention in control clinics CONCLUSIONS: Incorporating lay counselling services within collaborative care models does not produce superior nor inferior outcomes to models with specialist only counselling services. FUNDING: This work was supported by the UK Department for International Development [201446] as well as the National Institute of Mental Health, United States of America, grant number 1R01MH100470-01. Graham Thornicroft is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) South London at King's College London and King's College Hospital NHS Foundation Trust.

Overview of systematic reviews on strategies to improve treatment initiation, adherence to antiretroviral therapy and retention in care for people living with HIV: part 1.

OBJECTIVES: We sought to map the evidence and identify interventions that increase initiation of antiretroviral therapy, adherence to antiretroviral therapy and retention in care for people living with HIV at high risk for poor engagement in care. METHODS: We conducted an overview of systematic reviews and sought for evidence on vulnerable populations (men who have sex with men (MSM), African, Caribbean and Black (ACB) people, sex workers (SWs), people who inject drugs (PWID) and indigenous people). We searched PubMed, Excerpta Medica dataBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Web of Science and the Cochrane Library in November 2018. We screened, extracted data and assessed methodological quality in duplicate and present a narrative synthesis. RESULTS: We identified 2420 records of which only 98 systematic reviews were eligible. Overall, 65/98 (66.3%) were at low risk of bias. Systematic reviews focused on ACB (66/98; 67.3%), MSM (32/98; 32.7%), PWID (6/98; 6.1%), SWs and prisoners (both 4/98; 4.1%). Interventions were: mixed (37/98; 37.8%), digital (22/98; 22.4%), behavioural or educational (9/98; 9.2%), peer or community based (8/98; 8.2%), health system (7/98; 7.1%), medication modification (6/98; 6.1%), economic (4/98; 4.1%), pharmacy based (3/98; 3.1%) or task-shifting (2/98; 2.0%). Most of the reviews concluded that the interventions effective (69/98; 70.4%), 17.3% (17/98) were neutral or were indeterminate 12.2% (12/98). Knowledge gaps were the types of participants included in primary studies (vulnerable populations not included), poor research quality of primary studies and poorly tailored interventions (not designed for vulnerable populations). Digital, mixed and peer/community-based interventions were reported to be effective across the continuum of care. CONCLUSIONS: Interventions along the care cascade are mostly focused on adherence and do not sufficiently address all vulnerable populations.

Artemisinin-based combination therapy for treating uncomplicated malaria.

BACKGROUND: The World Health Organization recommends uncomplicated P. falciparum malaria is treated using Artemisinin-based Combination Therapy (ACT). This review aims to assist the decision making of malaria control programmes by providing an overview of the relative benefits and harms of the available options. OBJECTIVES: To compare the effects of ACTs with other available ACT and non-ACT combinations for treating uncomplicated P. falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS, and the metaRegister of Controlled Trials (mRCT) to March 2009. SELECTION CRITERIA: Randomized head to head trials of ACTs in uncomplicated P. falciparum malaria.This review is limited to: dihydroartemisinin-piperaquine; artesunate plus mefloquine; artemether-lumefantrine (six doses); artesunate plus amodiaquine; artesunate plus sulfadoxine-pyrimethamine and amodiaquine plus sulfadoxine-pyrimethamine. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy' and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on P. vivax, gametocytes, haemoglobin, and adverse events. MAIN RESULTS: Fifty studies met the inclusion criteria. All five ACTs achieved PCR adjusted failure rates of < 10%, in line with WHO recommendations, at most study sites.Dihydroartemisinin-piperaquine performed well compared to the ACTs in current use (PCR adjusted treatment failure versus artesunate plus mefloquine in Asia; RR 0.39, 95% CI 0.19 to 0.79; three trials, 1062 participants; versus artemether-lumefantrine in Africa; RR 0.39, 95% CI 0.24 to 0.64; three trials, 1136 participants).ACTs were superior to amodiaquine plus sulfadoxine-pyrimethamine in East Africa (PCR adjusted treatment failure versus artemether-lumefantrine; RR 0.12, 95% CI 0.06 to 0.24; two trials, 618 participants; versus AS+AQ; RR 0.44, 95% CI 0.22 to 0.89; three trials, 1515 participants).Dihydroartemisinin-piperaquine (RR 0.32, 95% CI 0.24 to 0.43; four trials, 1442 participants) and artesunate plus mefloquine (RR 0.30, 95% CI 0.21 to 0.41; four trials, 1003 participants) were more effective than artemether-lumefantrine at reducing the incidence of P.vivax over 42 days follow up. AUTHORS' CONCLUSIONS: Dihydroartemisinin-piperaquine is another effective first-line treatment for P. falciparum malaria.The performance of the non-ACT (amodiaquine plus sulfadoxine-pyrimethamine) falls below WHO recommendations for first-line therapy in parts of Africa.In areas where primaquine is not being used for radical cure of P. vivax, ACTs with long half-lives may provide some benefit.

Collaborative care for the detection and management of depression among adults with hypertension in South Africa: study protocol for the PRIME-SA randomised controlled trial.

BACKGROUND: The high co-morbidity of mental disorders, particularly depression, with non-communicable diseases (NCDs) such as cardiovascular disease (CVD), is concerning given the rising burden of NCDs globally, and the role depression plays in confounding prevention and treatment of NCDs. The objective of this randomised control trial (RCT) is to determine the real-world effectiveness of strengthened depression identification and management on depression outcomes in hypertensive patients attending primary health care (PHC) facilities in South Africa (SA). METHODS/DESIGN: The study design is a pragmatic, two-arm, parallel-cluster RCT, the unit of randomisation being the clinics, with outcomes being measured for individual participants. The 20 largest eligible clinics from one district in the North West Province are enrolled in the trial. Equal numbers of hypertensive patients (n = 50) identified as having depression using the Patient Health Questionnaire (PHQ-9) are enrolled from each clinic, making up a total of 1000 participants with 500 in each arm. The nurse clinicians in the control facilities receive the standard training in Primary Care 101 (PC101), a clinical decision support tool for integrated chronic care that includes guidelines for hypertension and depression care. Referral pathways available include referrals to PHC physicians, clinical or counselling psychologists and outpatient psychiatric and psychological services. In the intervention clinics, this training is supplemented with strengthened training in the depression components of PC101 as well as training in clinical communication skills for nurse-led chronic care. Referral pathways are strengthened through the introduction of a facility-based behavioural health counsellor, trained to provide structured manualised counselling for depression and adherence counselling for all chronic conditions. The primary outcome is defined as at least 50% reduction in PHQ-9 score measured at 6 months. DISCUSSION: This trial should provide evidence of the real world effectiveness of strengtheneddepression identification and collaborative management on health outcomes of hypertensive patients withcomorbid depression attending PHC facilities in South Africa. TRIAL REGISTRATION: South African National Clinical Trial Register: SANCTR ( http://www.sanctr.gov.za/SAClinicalTrials ) (DOH-27-0916-5051). Registered on 9 April 2015. ClinicalTrials.gov : ID: NCT02425124 . Registered on 22 April 2015.

Collaborative care for the detection and management of depression among adults receiving antiretroviral therapy in South Africa: study protocol for the CobALT randomised controlled trial.

BACKGROUND: The scale-up of antiretroviral treatment (ART) programmes has seen HIV/AIDS transition to a chronic condition characterised by high rates of comorbidity with tuberculosis, non-communicable diseases (NCDs) and mental health disorders. Depression is one such disorder that is associated with higher rates of non-adherence, progression to AIDS and greater mortality. Detection and treatment of comorbid depression is critical to achieve viral load suppression in more than 90% of those on ART and is in line with the recent 90-90-90 Joint United Nations Programme on HIV/AIDS (UNAIDS) targets. The CobALT trial aims to provide evidence on the effectiveness and cost-effectiveness of scalable interventions to reduce the treatment gap posed by the growing burden of depression among adults on lifelong ART. METHODS: The study design is a pragmatic, parallel group, stratified, cluster randomised trial in 40 clinics across two rural districts of the North West Province of South Africa. The unit of randomisation is the clinic, with outcomes measured among 2000 patients on ART who screen positive for depression using the Patient Health Questionnaire (PHQ-9). Control group clinics are implementing the South African Department of Health's Integrated Clinical Services Management model, which aims to reduce fragmentation of care in the context of rising multimorbidity, and which includes training in the Primary Care 101 (PC101) guide covering communicable diseases, NCDs, women's health and mental disorders. In intervention clinics, we supplemented this with training specifically in the mental health components of PC101 and clinical communications skills training to support nurse-led chronic care. We strengthened the referral pathways through the introduction of a clinic-based behavioural health counsellor equipped to provide manualised depression counselling (eight sessions, individual or group), as well as adherence counselling sessions (one session, individual). The co-primary patient outcomes are a reduction in PHQ-9 scores of at least 50% from baseline and viral load suppression rates measured at 6 and 12 months, respectively. DISCUSSION: The trial will provide real-world effectiveness of case detection and collaborative care for depression including facility-based counselling on the mental and physical outcomes for people on lifelong ART in resource-constrained settings. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02407691 ) registered on 19 March 2015; Pan African Clinical Trials Registry ( 201504001078347 ) registered on 19/03/2015; South African National Clinical Trials Register (SANCTR) ( DOH-27-0515-5048 ) NHREC number 4048 issued on 21/04/2015.