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Background: Community-based based antiretroviral treatment (ART) delivery is an important component of differentiated service delivery models in sub-Sahara Africa. However, community-based delivery systematically excludes new patients during their first six [...]

Objectives: Widespread access to antiretroviral therapy (ART) has substantially increased life expectancy in sub‐Saharan African countries. As a result, the rates of comorbidities and use of co‐medications among people living with HIV are increasing, necessitating a sound understanding of drug–drug interactions (DDIs). We aimed to assess the prevalence and management of DDIs with ART in a rural Tanzanian setting. Methods: We included consenting HIV‐positive adults initiating ART in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) between January 2013 and December 2016. DDIs were classified using www.hiv-druginteractions.org as red (contra‐indicated), amber (potential clinical relevance requiring dosage adjustment/monitoring), yellow (weak clinical significance unlikely to require further management) or green (no interaction). We assessed management of amber DDIs by evaluating monitoring of laboratory or clinical parameters, or changes in drug dosages. Results: Of 2069 participants, 1945 (94%) were prescribed at least one co‐medication during a median follow‐up of 1.8 years. Of these, 645 (33%) had at least one potentially clinically relevant DDI, with the highest grade being red in nine (< 1%) and amber in 636 (33%) participants. Of the 23 283 prescriptions, 19 (< 1%) and 1745 (7%) were classified as red and amber DDIs, respectively. Overall, 351 (2%) prescriptions were red DDIs or not appropriately managed amber DDIs. Conclusions: Co‐medication use was common in this rural sub‐Saharan cohort. A third of participants had DDIs requiring further management. Of the 9% of participants with not appropriately managed DDIs, most were with cardiovascular and analgesic drugs. This highlights the importance of physicians' awareness of DDIs for their recognition and management. [ABSTRACT FROM AUTHOR]

Objective: Rates of vertical HIV transmission between mother and child are low, allowing many HIV positive women to have children with near impunity. In this study, data from the Swiss Mother and Child HIV Cohort Study were used to describe maternal characteristics and their association with pregnancy outcomes in HIV positive women. Study design: HIV positive women were followed prospectively during their pregnancies and deliveries by anonymous questionnaires between January 2003 and October 2008. Adverse pregnancy outcomes included preterm delivery, preeclampsia and gestational diabetes mellitus. Results: This study included 266 HIV positive women, of which 67 (25.2%) were first diagnosed with HIV during pregnancy. Thirty percent (n=80) of the women had pregnancy complications after 24 weeks of gestation. Preterm delivery was noted in 72 (27%) patients. Other complications included preeclampsia (n=7; 2.6%) and gestational diabetes (n=7; 2.6%). Older maternal age was the only risk factor associated with adverse pregnancy outcomes (adjusted odds ratio: 1.06, 95% confidence interval 1.01-1.12, P=0.02). Conclusions: HIV positive women, especially with advanced maternal age, have high-risk pregnancies and should be monitored as in an interdisciplinary setting. The preponderance of initial HIV diagnosis during pregnancy confirms the importance of HIV screening in pregnant women. [ABSTRACT FROM AUTHOR]

BACKGROUND: Financial constraints and other forces affecting health care in many countries have led to nurses implicitly limiting their care in some instances. In the absence of an accepted definition and theoretical framework of implicit rationing of nursing care, a framework and the Basel Extent of Rationing of Nursing Care (BERNCA) instrument were developed. This instrument was used in the Swiss part of the International Hospital Outcome Study, in which implicit rationing of nursing care was studied. OBJECTIVE: To examine the validity and reliability of the newly developed BERNCA instrument. METHODS: Psychometric analysis was performed on data from 957 nurses in five Swiss acute care hospitals enrolled in a larger hospital organization study. An explanatory factor analysis with varimax rotation was used to investigate the instrument's internal structure, Spearman correlations were used to test relationships between implicit rationing and two related concepts, and Cronbach's alpha and interitem correlations were used to test the reliability of the scale. RESULTS: Expert feedback confirmed that the BERNCA covered the implicit rationing of nursing care domain adequately and that its questions were fully comprehensible. The single-factor solution confirmed the instrument's unidimensional internal structure. A moderate to strong correlation in the expected direction was found between the BERNCA implicit rationing data and the quality of the nurse work environment as measured by the Nursing Work Index-Revised, particularly the perceived adequacy of nursing resources, although a significant but low correlation was also shown with patient-to-nurse ratios. Cronbach's alphas (.93) and interitem correlations indicated internal consistency and homogeneity. DISCUSSION: Initial evidence of the validity and reliability of the BERNCA instrument was provided. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the Rationing of Nursing Care in Switzerland Study, implicit rationing of care was the only factor consistently significantly associated with all six studied patient outcomes. These results highlight the importance of rationing as a new system factor regarding patient safety and quality of care. Since at least some rationing of care appears inevitable, it is important to identify the thresholds of its influences in order to minimize its negative effects on patient outcomes. OBJECTIVES: To describe the levels of implicit rationing of nursing care in a sample of Swiss acute care hospitals and to identify clinically meaningful thresholds of rationing. DESIGN: Descriptive cross-sectional multi-center study. SETTINGS: Five Swiss-German and three Swiss-French acute care hospitals. PARTICIPANTS: 1338 nurses and 779 patients. METHODS: Implicit rationing of nursing care was measured using the newly developed Basel Extent of Rationing of Nursing Care (BERNCA) instrument. Other variables were measured using survey items from the International Hospital Outcomes Study battery. Data were summarized using appropriate descriptive measures, and logistic regression models were used to define a clinically meaningful rationing threshold level. RESULTS: For the studied patient outcomes, identified rationing threshold levels varied from 0.5 (i.e., between 0 ('never') and 1 ('rarely') to 2 ('sometimes')). Three of the identified patient outcomes (nosocomial infections, pressure ulcers, and patient satisfaction) were particularly sensitive to rationing, showing negative consequences anywhere it was consistently reported (i.e., average BERNCA scores of 0.5 or above). In other cases, increases in negative outcomes were first observed from the level of 1 (average ratings of rarely). CONCLUSIONS: Rationing scores generated using the BERNCA instrument provide a clinically meaningful method for tracking the correlates of low resources or difficulties in resource allocation on patient outcomes. Thresholds identified here provide parameters for administrators to respond to whenever rationing reports exceed the determined level of '0.5' or '1'. Since even very low levels of rationing had negative consequences on three of the six studied outcomes, it is advisable to treat consistent evidence of any rationing as a significant threat to patient safety and quality of care. [ABSTRACT FROM AUTHOR]

Effective and sustainable strategies are needed to address the burden of preventable deaths among children under-five in resource-constrained settings. The Tools for Integrated Management of Childhood Illness (TIMCI) project aims to support healthcare providers to identify and manage severe illness, whilst promoting resource stewardship, by introducing pulse oximetry and clinical decision support algorithms (CDSAs) to primary care facilities in India, Kenya, Senegal and Tanzania. Health impact is assessed through: a pragmatic parallel group, superiority cluster randomised controlled trial (RCT), with primary care facilities randomly allocated (1:1) in India to pulse oximetry or control, and (1:1:1) in Tanzania to pulse oximetry plus CDSA, pulse oximetry, or control; and through a quasi-experimental pre-post study in Kenya and Senegal. Devices are implemented with guidance and training, mentorship, and community engagement. Sociodemographic and clinical data are collected from caregivers and records of enrolled sick children aged 0-59 months at study facilities, with phone follow-up on Day 7 (and Day 28 in the RCT). The primary outcomes assessed for the RCT are severe complications (mortality and secondary hospitalisations) by Day 7 and primary hospitalisations (within 24 hours and with referral); and, for the pre-post study, referrals and antibiotic. Secondary outcomes on other aspects of health status, hypoxaemia, referral, follow-up and antimicrobial prescription are also evaluated. In all countries, embedded mixed-method studies further evaluate the effects of the intervention on care and care processes, implementation, cost and cost-effectiveness. Pilot and baseline studies started mid-2021, RCT and post-intervention mid-2022, with anticipated completion mid-2023 and first results late-2023. Study approval has been granted by all relevant institutional review boards, national and WHO ethical review committees. Findings will be shared with communities, healthcare providers, Ministries of Health and other local, national and international stakeholders to facilitate evidence-based decision-making on scale-up. Study registration : NCT04910750 and NCT05065320.

Objectives: To analyze weight changes associated with dolutegravir- versus efavirenz-based antiretroviral therapy (ART) in people living with HIV (PLHIV) in rural Tanzania, where undernutrition is prevalent., Design: Longitudinal, observational study of the prospective Kilombero and Ulanga Antiretroviral Cohort (KIULARCO)., Methods: We included adult, ART-naïve, non-pregnant PLHIV initiating efavirenz-based ART 12/2016-02/2019 or dolutegravir-based ART 03/2019-12/2022. We used multivariable linear mixed-effects models to assess adjusted weight changes during 18 months after ART start and Cox regression models to assess factors associated with incident obesity, weight gain ≥10% and hypertension., Results: Of 1,205 PLHIV at ART start (median age 40 years (IQR 32-48); 719 (59.7%) females), 166 (13.8%) individuals were underweight and 317 (26.3%) overweight/obese; 621 (51.5%) initiated efavirenz-based and 584 (48.5%) dolutegravir-based ART. After 18 months, estimated weight gain was 5.1 kg (95%CI 4.7-5.5) in the dolutegravir versus 4.0 kg (95%CI 3.7-4.4) in the efavirenz group. The weight gain difference between treatment groups was high in men (1.7 kg (95%CI 0.8-2.6; p < 0.001), in those aged 30-49 years (1.5 kg (0.8-2.1); p < 0.001) and those with CD4 counts ≥500/ul (2.5 kg (1.4 - 3.7), p < 0.001). Cumulative obesity incidence at 18 months was 10.9% (95%CI 8.3-14.0) in the dolutegravir and 5.1% (95%CI 3.6-7.1) in the efavirenz group. Associated factors were dolutegravir and a pre-ART body mass index (BMI) of 25-29 kg/m2. Dolutegravir and age, but not weight gain were associated with incident of hypertension., Conclusions: Dolutegravir-based ART was associated with more weight gain, higher obesity and hypertension - especially in those with a higher pre-ART BMI compared to efavirenz-based regimens., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: To improve tuberculosis case-finding, rapid, non-sputum triage tests need to be developed according to the World Health Organization target product profile (TPP) (>90% sensitivity, >70% specificity). We prospectively evaluated and compared artificial intelligence-based, computer-aided detection software, CAD4TBv7, and C-reactive protein assay (CRP) as triage tests at health facilities in Lesotho and South Africa., Methods: Adults (≥18 years) presenting with ≥1 of the 4 cardinal tuberculosis symptoms were consecutively recruited between February 2021 and April 2022. After informed consent, each participant underwent a digital chest X-ray for CAD4TBv7 and a CRP test. Participants provided 1 sputum sample for Xpert MTB/RIF Ultra and Xpert MTB/RIF and 1 for liquid culture. Additionally, an expert radiologist read the chest X-rays via teleradiology. For primary analysis, a composite microbiological reference standard (ie, positive culture or Xpert Ultra) was used., Results: We enrolled 1392 participants, 48% were people with HIV and 24% had previously tuberculosis. The receiver operating characteristic curve for CAD4TBv7 and CRP showed an area under the curve of .87 (95% CI: .84-.91) and .80 (95% CI: .76-.84), respectively. At thresholds corresponding to 90% sensitivity, specificity was 68.2% (95% CI: 65.4-71.0%) and 38.2% (95% CI: 35.3-41.1%) for CAD4TBv7 and CRP, respectively. CAD4TBv7 detected tuberculosis as well as an expert radiologist. CAD4TBv7 almost met the TPP criteria for tuberculosis triage., Conclusions: CAD4TBv7 is accurate as a triage test for patients with tuberculosis symptoms from areas with a high tuberculosis and HIV burden. The role of CRP in tuberculosis triage requires further research., Clinical Trials Registration: Clinicaltrials.gov identifier: NCT04666311., Competing Interests: Potential conflicts of interest. B. v. G. reports that his group received royalties from Delft Imaging Systems and that he holds shares in Thirona. K. R., B. v. G., A. v. H., A. S., K. M., L. L., T. Z., B. K. M. J., S. B., T. M., and M. K. report support related to this work from the European and Developing Countries Clinical Trials Partnership 2 (EDCTP2). K. R. reports grants unrelated to this work from EDCTP2 and Horizon 2020, as well as unpaid participation on a data safety monitoring board or scientific advisory board for evaluation of new TB diagnostics. S. B. reports a grant unrelated to this work from the National Institutes of Health (NIH) and travel support from MSD. T. M. reports travel support from MSD. N. D. L. reports support for travel from ViiV Healthcare and Gilead Sciences Sarl as well as for attending a board meeting from ViiV Healthcare and Pharming. S. B. and T. M. report travel support from MSD. The other authors report no potential conflict of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Children and adolescents with HIV taking antiretroviral therapy (ART) have high rates of viraemia. We assessed if genotypic resistance testing (GRT) to inform onward treatment improved treatment outcomes in Lesotho and Tanzania, two countries with little access to GRT., Methods: The Genotype-Informed Versus Empirical Management of Viremia (GIVE MOVE) open-label, parallel-group randomised controlled trial enrolled children and adolescents with HIV between the ages of 6 months and 19 years, taking ART, and with a viral load at least 400 copies per mL. Participants were recruited from ten clinical centres and hospitals in Lesotho and Tanzania. Participants were electronically randomly allocated 1:1 to receive either GRT with expert recommendation (GRT group) or repeat viral-load testing and empirical onward treatment (usual care group). Participants and study staff were not masked, but the endpoint committee and laboratory staff conducting viral-load testing were. Participants in both groups received at least three sessions of enhanced adherence counselling, and in the GRT group, blood for GRT assessed via Sanger sequencing was drawn at enrolment. The composite primary endpoint was death, hospitalisation, a new WHO HIV clinical stage 4 event, or not having documented viral suppression of less than 50 copies per mL at 36 weeks in the modified intention-to-treat population, which excluded participants who were retrospectively found to be ineligible after randomisation. Serious adverse events were analysed in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT04233242) and the trial status is completed., Findings: Between March 3, 2020, and July 5, 2022, 286 participants were enrolled and 284 were included in the modified intention-to-treat analysis (144 in the GRT group and 140 in the usual care group). Of these participants, 158 (56%) were female and 126 (44%) were male. Five (3%) in the GRT group and four (3%) in the usual care group did not complete follow-up but were included in the primary analysis. The median age across both groups was 14 years (IQR 9-16). The composite primary endpoint occurred in 67 (47%) participants in the GRT group and 73 (52%) in the usual care group (adjusted odds ratio 0·79 [95% CI 0·49 to 1·27]; adjusted risk difference -0·06 [95% CI -0·17 to 0·06]; p=0·34); all participants reaching the composite primary endpoint had no documented viral suppression at 36 weeks. No deaths were recorded, and only one clinical stage 4 event requiring hospitalisation occurred (in the usual care group); this was the only serious adverse event recorded in the study., Interpretation: GRT-informed management did not significantly improve treatment outcomes for children and adolescents with viraemia while taking ART., Funding: Fondation Botnar, Swiss National Science Foundation, and Gottfried and Julia Bangerter-Rhyner Foundation., Translations: For the Sesotho and Swahili translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests NDL reports having received travel grants to conferences from Gilead Sciences and ViiV Healthcare, and his division received honoraria for consultancies from ViiV Healthcare and for participation in a data safety monitoring board from Pharming. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Estimation of prevalence and diagnostic test accuracy in tuberculosis (TB) prevalence surveys suffer from reference standard and verification biases. The former is attributed to the imperfect reference test used to bacteriologically confirm TB disease. The latter occurs when only the participants screening positive for any TB-compatible symptom or chest X-ray abnormality are selected for bacteriological testing (verification). Bayesian latent class analysis (LCA) alleviates the reference standard bias but suffers verification bias in TB prevalence surveys. This work aims to identify best-practice approaches to simultaneously alleviate the reference standard and verification biases in the estimates of pulmonary TB prevalence and diagnostic test performance in TB prevalence surveys., Methods: We performed a secondary analysis of 9869 participants aged ≥15 years from a community-based multimorbidity screening study in a rural district of KwaZulu-Natal, South Africa (Vukuzazi study). Participants were eligible for bacteriological testing using Xpert Ultra and culture if they reported any cardinal TB symptom or had an abnormal chest X-ray finding. We conducted Bayesian LCA in five ways to handle the unverified individuals: (i) complete-case analysis, (ii) analysis assuming the unverified individuals would be negative if bacteriologically tested, (iii) analysis of multiply-imputed datasets with imputation of the missing bacteriological test results for the unverified individuals using multivariate imputation via chained equations (MICE), and simultaneous imputation of the missing bacteriological test results in the analysis model assuming the missing bacteriological test results were (iv) missing at random (MAR), and (v) missing not at random (MNAR). We compared the results of (i)-(iii) to the analysis based on a composite reference standard (CRS) of Xpert Ultra and culture. Through simulation with an overall true prevalence of 2.0%, we evaluated the ability of the models to alleviate both biases simultaneously., Results: Based on simulation, Bayesian LCA with simultaneous imputation of the missing bacteriological test results under the assumption that the missing data are MAR and MNAR alleviate the reference standard and verification biases. CRS-based analysis and Bayesian LCA assuming the unverified are negative for TB alleviate the biases only when the true overall prevalence is <3.0%. Complete-case analysis produced biased estimates. In the Vukuzazi study, Bayesian LCA with simultaneous imputation of the missing bacteriological test results under the MAR and MNAR assumptions produced overall PTB prevalence of 0.9% (95% Credible Interval (CrI): 0.6-1.9) and 0.7% (95% CrI: 0.5-1.1) respectively alongside realistic estimates of overall diagnostic test sensitivity and specificity with substantially overlapping 95% CrI. The CRS-based analysis and Bayesian LCA assuming the unverified were negative for TB produced 0.7% (95% CrI: 0.5-0.9) and 0.7% (95% CrI: 0.5-1.2) overall PTB prevalence respectively with realistic estimates of overall diagnostic test sensitivity and specificity. Unlike CRS-based analysis, Bayesian LCA of multiply-imputed data using MICE mitigates both biases., Conclusion: The findings demonstrate the efficacy of these advanced techniques in alleviating the reference standard and verification biases, enhancing the robustness of community-based screening programs. Imputing missing values as negative for bacteriological tests is plausible under realistic assumptions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Keter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The use of antigen rapid tests (Ag-RDTs) for self-testing is an important element of the COVID-19 control strategy and has been widely supported. However, scale-up of self-testing for COVID-19 in sub-Saharan Africa is still insufficient and there is limited evidence on the acceptability of self-testing and agreement between Ag-RDT self-testing and Ag-RDT testing by professional users. A joint collaboration (Botnar Research Centre for Child Health-European & Developing countries Clinical Trials Partnership)was established between Lesotho and Zambia to address these gaps in relation to Ag-RDT self-testing and contribute to increasing its use in the region., Methods: A cross-sectional study was conducted with qualitative and quantitative data analysis. Firstly, 14 in-depth cognitive interviews (5 in Zambia and 9 in Lesotho) were performed to assess the participants' understanding of the instructions for use (IFU) for self-testing. In a second step, evaluation of test agreement between Ag-RDT self-testing and Ag-RDT testing by professional user using SD Biosensor STANDARD Q COVID-19 Ag-RDT was performed. In Zambia, usability and acceptability of self-testing were also assessed., Results: Cognitive interviews in Lesotho and Zambia showed overall good understanding of IFU. In Zambia, acceptability of self-testing was high, though some participants had difficulties in conducting certain steps in the IFU correctly. Agreement between Ag-RDT self-test and Ag-RDT by professional users in Lesotho (428 participants) and Zambia (1136 participants) was high, 97.3% (403/414, 95% CI: 95.3-98.7) and 99.8% (1116/1118, 95% CI: 99.4-100) respectively., Conclusion: Findings from this study support the use of Ag-RDT self-testing within COVID-19 control strategies in sub-Saharan Africa, contributing to increase the testing capacity and access in hard-to reach settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bresser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In absence of contraindications, same-day initiation (SDI) of antiretroviral therapy (ART) is recommended for people testing HIV-positive who are ready to start treatment. Until 2021, World Health Organization (WHO) guidelines considered the presence of TB symptoms (presumptive TB) a contraindication to SDI due to the risk of TB-immune reconstitution inflammatory syndrome (TB-IRIS). To reduce TB-IRIS risk, ART initiation was recommended to be postponed until results of TB investigations were available, and TB treatment initiated if active TB was confirmed. In 2021, the WHO guidelines changed to recommending SDI even in the presence of TB symptoms without awaiting results of TB investigations based on the assumption that TB investigations often unnecessarily delay ART initiation, increasing the risk for pre-ART attrition from care, and noting that the clinical relevance of TB-IRIS outside the central nervous system remains unclear. However, this guideline change was not based on conclusive evidence, and it remains unclear whether SDI of ART or TB test results should be prioritized in people with HIV (PWH) and presumptive TB., Design and Methods: SaDAPT is an open-label, pragmatic, parallel, 1:1 individually randomized, non-inferiority trial comparing two strategies for the timing of ART initiation in PWH with presumptive TB ("ART first" versus "TB results first"). PWH in Lesotho and Malawi, aged 12 years and older (re)initiating ART who have at least one TB symptom (cough, fever, night sweats or weight loss) and no signs of intracranial infection are eligible. After a baseline assessment, participants in the "ART first" arm will be offered SDI of ART, while those in the "TB results first" arm will be offered ART only after active TB has been confirmed or refuted. We hypothesize that the "ART first" approach is safe and non-inferior to the "TB results first" approach with regard to HIV viral suppression (<400 copies/ml) six months after enrolment. Secondary outcomes include retention in care and adverse events consistent with TB-IRIS., Expected Outcomes: SaDAPT will provide evidence on the safety and effects of SDI of ART in PWH with presumptive TB in a pragmatic clinical trial setting., Trial Registration: The trial has been registered on clinicaltrials.gov (NCT05452616; July 11 2022)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gerber et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This scoping review aims to identify and synthesise existing statistical methods used to assess the progress of HIV treatment programmes in terms of the HIV cascade and continuum of care among people living with HIV (PLHIV)., Design: Systematic scoping review., Data Sources: Published articles were retrieved from PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Complete and Excerpta Medica dataBASE (EMBASE) databases between April and July 2022. We also strategically search using the Google Scholar search engine and reference lists of published articles., Eligibility Criteria: This scoping review included original English articles that estimated and described the HIV cascade and continuum of care progress in PLHIV. The review considered quantitative articles that evaluated either HIV care cascade progress in terms of the Joint United Nations Programme on HIV and AIDS targets or the dynamics of engagement in HIV care., Data Extraction and Synthesis: The first author and the librarian developed database search queries and screened the retrieved titles and abstracts. Two independent reviewers and the first author extracted data using a standardised data extraction tool. The data analysis was descriptive and the findings are presented in tables and visuals., Results: This review included 300 articles. Cross-sectional study design methods were the most commonly used to assess the HIV care cascade (n=279, 93%). In cross-sectional and longitudinal studies, the majority used proportions to describe individuals at each cascade stage (276/279 (99%) and 20/21 (95%), respectively). In longitudinal studies, the time spent in cascade stages, transition probabilities and cumulative incidence functions was estimated. The logistic regression model was common in both cross-sectional (101/279, 36%) and longitudinal studies (7/21, 33%). Of the 21 articles that used a longitudinal design, six articles used multistate models, which included non-parametric, parametric, continuous-time, time-homogeneous and discrete-time multistate Markov models., Conclusions: Most literature on the HIV cascade and continuum of care arises from cross-sectional studies. The use of longitudinal study design methods in the HIV cascade is growing because such methods can provide additional information about transition dynamics along the cascade. Therefore, a methodological guide for applying different types of longitudinal design methods to the HIV continuum of care assessments is warranted., Competing Interests: Competing interests: ‘Yes, there are competing interests for one or more authors and I have provided a Competing Interests statement in my manuscript and in the box below’, (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Artificial intelligence (AI) systems for detection of COVID-19 using chest X-Ray (CXR) imaging and point-of-care blood tests were applied to data from four low resource African settings. The performance of these systems to detect COVID-19 using various input data was analysed and compared with antigen-based rapid diagnostic tests. Participants were tested using the gold standard of RT-PCR test (nasopharyngeal swab) to determine whether they were infected with SARS-CoV-2. A total of 3737 (260 RT-PCR positive) participants were included. In our cohort, AI for CXR images was a poor predictor of COVID-19 (AUC = 0.60), since the majority of positive cases had mild symptoms and no visible pneumonia in the lungs. AI systems using differential white blood cell counts (WBC), or a combination of WBC and C-Reactive Protein (CRP) both achieved an AUC of 0.74 with a suggested optimal cut-off point at 83% sensitivity and 63% specificity. The antigen-RDT tests in this trial obtained 65% sensitivity at 98% specificity. This study is the first to validate AI tools for COVID-19 detection in an African setting. It demonstrates that screening for COVID-19 using AI with point-of-care blood tests is feasible and can operate at a higher sensitivity level than antigen testing., (© 2023. The Author(s).)

Introduction: Increased body weight is an important risk factor for cardiovascular disease and is increasingly reported as a health problem in people living with HIV (PLHIV). There is limited data from rural sub-Saharan Africa, where malnutrition usually presents with both over- and undernutrition. We aimed to determine the prevalence and risk factors of underweight and overweight/obesity in PLHIV enrolled in a cohort in rural Tanzania before the introduction of integrase inhibitors., Methods: This nested study of the prospective Kilombero and Ulanga Antiretroviral Cohort included adults aged ≥19 years initiated on antiretroviral therapy between 01/2013 and 12/2018 with follow-up through 06/2019. Body Mass Index (BMI) was classified as underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), or overweight/obese (≥25.0 kg/m2). Stratified piecewise linear mixed models were used to assess the association between baseline characteristics and follow-up BMI. Cox proportional hazard models were used to assess the association between time-updated BMI and death/loss to follow-up (LTFU)., Results: Among 2,129 patients, 22,027 BMI measurements (median 9 measurements: interquartile range 5-15) were analysed. At baseline, 398 (19%) patients were underweight and 356 (17%) were overweight/obese. The majority of patients were female (n = 1249; 59%), and aged 35-44 years (779; 37%). During the first 9 months, for every three additional months on antiretroviral therapy, BMI increased by 2% (95% confidence interval 1-2%, p<0.0001) among patients underweight at baseline and by 0.7% (0.5-0.6%, p<0.0001) among participants with normal BMI. Over a median of 20 months of follow-up, 107 (5%) patients died and 592 (28%) were LTFU. Being underweight was associated with >2 times the hazard of death/LTFU compared to participants with normal BMI., Conclusion: We found a double burden of malnutrition, with underweight being an independent predictor of mortality. Monitoring and measures to address both states of malnutrition among PLHIV should be integrated into routine HIV care., Competing Interests: I have read the journal’s policy and the author of this manuscript has the following competing interests: Emilio Letang is a full-time employee ViiV Healthcare since May 2021. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Other authors have declared that no competing interests exist., (Copyright: © 2023 Kalinjuma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The surge of the COVID-19 pandemic challenged health services globally, and in Lesotho, the HIV and tuberculosis (TB) services were similarly affected. Integrated, multi-disease diagnostic services were proposed solutions to mitigate these disruptions. We describe and evaluate the effect of an integrated, hospital-based COVID-19, TB and HIV screening and diagnostic model in two rural districts in Lesotho, during the period between December 2020 and August 2022. Adults, hospital staff, and children above 5 years attending two hospitals were pre-screened for COVID-19 and TB symptoms. After a positive pre-screening, participants were offered to enroll in a service model that included clinical evaluation, chest radiography, SARS-CoV-2, TB, and HIV testing. Participants diagnosed with COVID-19, TB, or HIV were contacted after 28 days to evaluate their health status and linkage to HIV and/or TB care services. Of the 179160 participants pre-screened, 6623(3.7%) pre-screened positive, and 4371(66%) were enrolled in this service model. Of the total 458 diagnoses, only 17 happened in children. One positive rapid antigen test for SARS-CoV-2 was found per 11 participants enrolled, one Xpert-positive TB case was diagnosed per 85 people enrolled, and 1 new HIV diagnosis was done per 182 people enrolled. Of the 321(82.9%) participants contacted after 28 days of diagnosis, 304(94.7%) reported to be healthy. Of the individuals that were newly diagnosed with HIV or TB, 18/24(75.0%) and 46/51(90.1%) started treatment within 28 days of the diagnosis. This screening and diagnostic model successfully maintained same-day, integrated COVID-19, TB, and HIV testing services, despite frequent disruptions caused by the surge of COVID-19 waves, healthcare seeking patterns, and the volatile context (social measures, travel restrictions, population lockdowns). There were positive effects in avoiding diagnostic delays and ensuring linkage to services, however, diagnostic yields for adults and children were low. To inform future preparedness plans, research will need to identify essential health interventions and how to optimize them along each phase of the emergency response., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Katende et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Incomplete antiretroviral therapy (ART) adherence has been linked to deleterious immunologic, inflammatory, and clinical consequences, even among virally suppressed (<50 copies/mL) persons with human immunodeficiency virus (PWH). The impact of improving adherence in the risk of severe non-AIDS events (SNAEs) and death in this population is unknown., Methods: We estimated the reduction in the risk of SNAEs or death resulting from an increase in ART adherence by (1) applying existing data on the association between adherence with high residual inflammation/coagulopathy in virally suppressed PWH, and (2) using a Cox proportional hazards model derived from changes in plasma interleukin 6 (IL-6) and D-dimer from 3 randomized clinical trials. Comparatively, assuming 100% ART adherence in a PWH who achieves viral suppression, we estimated the number of persons in whom a decrease in adherence to <100% would need to be observed for an additional SNAE or death event to occur during 3- and 5-year follow-up., Results: Increasing ART adherence to 100% in PWH who are suppressed on ART despite imperfect adherence translated into a 6%-37% reduction in the risk of SNAEs or death. Comparatively, based on an anticipated 12% increase in IL-6, 254 and 165 PWH would need to decrease their adherence from 100% to <100% for an additional event to occur over 3- and 5-year follow-up, respectively., Conclusions: Modest gains in ART adherence could have clinical benefits beyond virologic suppression. Increasing ART adherence (eg, via an intervention or switch to long-acting ART) in PWH who remain virally suppressed despite incomplete adherence should be evaluated., Competing Interests: Potential conflicts of interest. J. R. C.-M. has received research support (investigator initiated) from Gilead Sciences, paid to his institution. M. C.'s institution has received research grants from Gilead, MSD, and ViiV Healthcare and travel grants from Gilead. S. S.-V. has received research grants from Gilead Sciences and MSD, and nonfinancial support from Gilead Sciences and ViiV Healthcare. J. E. H. has been a paid consultant for Merck and owns stock in Natera. T. T. B. has served as consultant to Merck, ViiV Healthcare, and Janssen. C. C is a full-time employee of Gilead Sciences. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Monitoring HIV viral load (HVL) in people living with HIV (PLHIV) on antiretroviral therapy (ART) is recommended by the World Health Organization. Implementation of HVL testing programs have been affected by logistic and organizational challenges. Here we describe the HVL monitoring cascade in a rural setting in Tanzania and compare turnaround times (TAT) between an on-site and a referral laboratory., Methods: In a nested study of the prospective Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) we included PLHIV aged ≥ 15 years, on ART for ≥ 6 months after implementation of routine HVL monitoring in 2017. We assessed proportions of PLHIV with a blood sample taken for HVL, whose results came back, and who were virally suppressed (HVL < 1000 copies/mL) or unsuppressed (HVL ≥ 1000 copies/mL). We described the proportion of PLHIV with unsuppressed HVL and adequate measures taken as per national guidelines and outcomes among those with low-level viremia (LLV; 100-999 copies/mL). We compare TAT between on-site and referral laboratories by Wilcoxon rank sum tests., Results: From 2017 to 2020, among 4,454 PLHIV, 4,238 (95%) had a blood sample taken and 4,177 (99%) of those had a result. Of those, 3,683 (88%) were virally suppressed. In the 494 (12%) unsuppressed PLHIV, 425 (86%) had a follow-up HVL (102 (24%) within 4 months and 158 (37%) had virologic failure. Of these, 103 (65%) were already on second-line ART and 32/55 (58%) switched from first- to second-line ART after a median of 7.7 months (IQR 4.7-12.7). In the 371 (9%) PLHIV with LLV, 327 (88%) had a follow-up HVL. Of these, 267 (82%) resuppressed to < 100 copies/ml, 41 (13%) had persistent LLV and 19 (6%) had unsuppressed HVL. The median TAT for return of HVL results was 21 days (IQR 13-39) at the on-site versus 59 days (IQR 27-99) at the referral laboratory (p < 0.001) with PLHIV receiving the HVL results after a median of 91 days (IQR 36-94; similar for both laboratories)., Conclusion: Robust HVL monitoring is achievable in remote resource-limited settings. More focus is needed on care models for PLHIV with high viral loads to timely address results from routine HVL monitoring., (© 2023. The Author(s).)

Objectives: To assess the real-world diagnostic performance of nasal and nasopharyngeal swabs for SD Biosensor STANDARD Q COVID-19 Antigen Rapid Diagnostic Test (Ag-RDT)., Methods: Individuals ≥5 years with COVID-19 compatible symptoms or history of exposure to SARS-CoV-2 presenting at hospitals in Lesotho received two nasopharyngeal and one nasal swab. Ag-RDT from nasal and nasopharyngeal swabs were performed as point-of-care on site, the second nasopharyngeal swab used for polymerase chain reaction (PCR) as the reference standard., Results: Out of 2198 participants enrolled, 2131 had a valid PCR result (61% female, median age 41 years, 8% children), 84.5% were symptomatic. Overall PCR positivity rate was 5.8%. The sensitivity for nasopharyngeal, nasal, and combined nasal and nasopharyngeal Ag-RDT result was 70.2% (95%CI: 61.3-78.0), 67.3% (57.3-76.3) and 74.4% (65.5-82.0), respectively. The respective specificity was 97.9% (97.1-98.4), 97.9% (97.2-98.5) and 97.5% (96.7-98.2). For both sampling modalities, sensitivity was higher in participants with symptom duration ≤ 3days versus ≤ 7days. Agreement between nasal and nasopharyngeal Ag-RDT was 99.4%., Conclusions: The STANDARD Q Ag-RDT showed high specificity. Sensitivity was, however, below the WHO recommended minimum requirement of ≥ 80%. The high agreement between nasal and nasopharyngeal sampling suggests that for Ag-RDT nasal sampling is a good alternative to nasopharyngeal sampling., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Labhardt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: HIV programmes across many countries in Africa have recently transitioned people living with HIV from efavirenz (EFV)- to dolutegravir (DTG)-containing antiretroviral therapy (ART). As both drugs are associated with neuropsychiatric adverse effects, this study assessed the mental health and HIV/ART-associated symptoms of people living with HIV before and after transition to DTG., Methods: The prospective DO-REAL cohort enrolled people starting DTG-based ART in Lesotho from February to December 2020. For this analysis within DO-REAL, we included adults changing from tenofovir disoproxil fumarate (TDF)/lamivudine (3TC)/EFV to TDF/3TC/DTG within first-line therapy. At transition and 16 weeks thereafter, participants completed the Patient Health Questionnaire-9 (PHQ-9; depression screening), the 12-item Short-Form Health Survey (SF-12; mental and physical health), and a modified HIV Symptom Index (mHSI; HIV/ART-related symptoms). We also assessed weight change. We used McNemar tests with Bonferroni corrections to assess binary outcomes., Clinicaltrials: gov: NCT04238767., Results: Among 1228 participants, 1131 completed follow-up. Of these, 60.0% were female, the median age was 46 years (interquartile range [IQR] 38-55), and the median time taking ART was 5.7 years (IQR 3.5-8.9). No change was observed for weight or overall PHQ-9 or SF-12 outcomes. However, three mHSI items decreased at follow-up: 'feeling sad/down/depressed' (bothered 6.0% vs. 3.3% of participants at least 'a little' before vs. after transition; adjusted p = 0.048); 'feeling nervous/anxious' (7.4% vs. 3.4%; adjusted p = 0.0009); and 'nightmares, strange/vivid dreams' (6.3% vs. 3.5%; adjusted p = 0.027). Individual PHQ-9 or SF-12 items also improved. Being symptom free across all measures increased from 5.1% to 11.4% (p < 0.0001)., Conclusions: We observed no negative impacts and potential moderate improvements with DTG, providing further support for the rollout of DTG., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Southern and Eastern Africa is home to more than 2.1 million young people aged 15 to 24 years living with HIV. As compared with other age groups, this population group has poorer outcomes along the HIV care cascade. Young people living with HIV and the research team co-created the PEBRA (Peer Educator-Based Refill of ART) care model. In PEBRA, a peer educator (PE) delivered services as per regularly assessed patient preferences for medication pick-up, short message service (SMS) notifications, and psychosocial support. The cluster-randomized trial compared PEBRA model versus standard clinic care (no PE and ART refill done by nurses) in 3 districts in Lesotho., Methods and Findings: Individuals taking antiretroviral therapy (ART) aged 15 to 24 years at 20 clinics (clusters) were eligible. In the 10 clinics randomized to the intervention arm, participants were offered the PEBRA model, coordinated by a trained PE and supported by an eHealth application (PEBRApp). In the 10 control clusters, participants received standard nurse-coordinated care without any service coordination by a PE. The primary endpoint was 12-month viral suppression below 20 copies/mL. Analyses were intention-to-treat and adjusted for sex. From November 6, 2019 to February 4, 2020, we enrolled 307 individuals (150 intervention, 157 control; 218 [71%] female, median age 19 years [interquartile range, IQR, 17 to 22]). At 12 months, 99 of 150 (66%) participants in the intervention versus 95 of 157 (61%) participants in the control arm had viral suppression (adjusted odds ratio (OR) 1.27; 95% confidence interval [CI] [0.79 to 2.03]; p = 0.327); 4 of 150 (2.7%) versus 1 of 157 (0.6%) had died (adjusted OR 4.12; 95% CI [0.45 to 37.62]; p = 0.210); and 12 of 150 (8%) versus 23 of 157 (14.7%) had transferred out (adjusted OR 0.53; 95% CI [0.25 to 1.13]; p = 0.099). There were no significant differences between arms in other secondary outcomes. Twenty participants (11 in intervention and 9 in control) were lost to follow-up over the entire study period. The main limitation was that the data collectors in the control clusters were also young peers; however, they used a restricted version of the PEBRApp to collect data and thus were not able to provide the PEBRA model. The trial was prospectively registered on ClinicalTrials.gov (NCT03969030)., Conclusions: Preference-based peer-coordinated care for young people living with HIV, compared to nurse-based care only, did not lead to conclusive evidence for an effect on viral suppression., Trial Registration: clinicaltrials.gov, NCT03969030, https://clinicaltrials.gov/ct2/show/NCT03969030., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kopo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bioaerosol capture and analysis is emerging as a non-invasive diagnostic method for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this proof-of-concept study conducted in Lesotho, we evaluated the novel and simple AL2 bioaerosol detection device in comparison to conventional nasopharyngeal sampling methods. We demonstrated for the first time that SARS-CoV-2 can be detected using the AL2 bioaerosol capture device. However, studies with a larger sample size are needed to further evaluate this bioaerosol capture device for the detection of SARS-CoV-2., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. AL2 Impact and 3M Company provided the bioaerosol capture devices and gave technical advice, but were not involved in data analysis., (© 2022 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.)

Objectives: Pill count is used to assess drug adherence in people living with HIV (PLHIV). Carrying a pillbox is associated with fear of concealment and stigma and might indicate poor adherence and predict someone who will be lost to follow-up (LTFU). We therefore assessed the association between pillbox return and being LTFU in rural Tanzania., Methods: This is a nested study of the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). We included PLHIV aged ≥ 18 years enrolled in KIULARCO between January 2013 and March 2019 with follow-up through January 2020, who were on antiretroviral treatment (ART) for ≥ 6 months. Baseline was defined as the latest ART initiation or KIULARCO enrolment. We determined the association between time-dependent failed pillbox return updated at every visit and LTFU using Kaplan-Meier estimation and Cox models., Results: Among 2552 PLHIV included in the study, 1735 (68.0%) were female, 959 (40.3%) had a WHO stage III/IV and 1487 (66.4%) had a CD4 cell count < 350 cells/µL. The median age was 38.4 years [interquartile range (IQR): 31.7-46.2]. During a median follow-up of 33.1 months (IQR: 17.5-52.4), 909 (35.6%) participants were LTFU, 43 (1.7%) died and 194 (7.6%) had transferred to another clinic. The probability of being LTFU was higher among PLHIV with failed pillbox return than among those who returned their pillbox [30.0%, 95% confidence interval (CI): 26.8-33.2% vs. 19.4%, 95% CI: 17.4-21.6%, respectively, at 24 months (hazard ratio = 1.67, 95% CI: 1.46-1.90; p < 0.001)]., Conclusions: Failed pillbox return was associated with a higher risk of being LTFU and could be used as a simple tool to identify PLHIV for appropriate interventions to reduce their chance of being LTFU., (© 2021 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Children living with HIV and taking antiretroviral therapy (ART) are a priority group for routine viral load (VL) monitoring. As per Lesotho guidelines, a VL ≥1000 copies/mL ("unsuppressed") should trigger adherence counseling and a follow-up VL; 2 consecutive unsuppressed VLs ("virologic failure") qualify for switching to second-line ART, with some exceptions. Here, we describe the pediatric VL cascade in Lesotho., Methods: In a prospective open cohort study comprising routine VL results from 22 clinics in Lesotho, we assessed outcomes along the VL cascade for children who had at least 1 VL test from January 2016 through June 2020. Data were censored on February 10, 2021., Results: In total, 1215 children received 5443 VL tests. The median age was 10 years (interquartile range 7-13) and 627/1215 (52%) were female; 362/1215 (30%) had at least 1 unsuppressed VL. A follow-up VL was available for 325/362 (90%), although only for 159/362 (44%) within 6 months of the first unsuppressed VL. Of those with a follow-up VL, 172/329 (53%) had virologic failure and 123/329 (37%) qualified for switching to second-line ART. Of these, 55/123 (45%) were ever switched, although only 9/123 (7%) were switched within 12 weeks of the follow-up VL. Delays were more pronounced in rural facilities. Overall, 100/362 (28%) children with an unsuppressed VL received a timely follow-up VL and, if required, a timely regimen switch., Conclusions: Despite access to VL monitoring, clinical management was suboptimal. HIV programs should prioritize timely clinical action to maximize the benefits of VL monitoring., Competing Interests: T.K. reports advisory board membership fees from ViiV and Gilead for work outside this study. N.D.L. reports having received travel grants to attend IAS, AIDS, and CROI conferences from Gilead Sciences Sarl. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Reports on the epidemiology and mortality of retroperitoneal soft tissue sarcoma (RSTS) in Switzerland are scarce. This study investigates the incidence and outcomes of surgically treated RSTS inpatients in Switzerland depending on the hospital type and size., Methods: Data from the Swiss Federal Statistical Office were used to conduct a retrospective analysis of all RSTS inpatients and hospitalizations in Switzerland between 2005 and 2015. RSTS was identified by the code C48.x of the International Classification of Diseases (ICD-10). Sarcoma centers were identified by the annual total number of sarcoma patients (> 50 patients/year). The analysis of yearly incidence, age distribution as well as in-hospital complication and mortality was performed for non- and surgical-treated patients. A centralization of treating sarcoma patients was analyzed by the trend of hospitalizations in sarcoma centers and high-volume hospitals., Results: During 2005-2015, 2.801 hospitalizations (1651 patients) were admitted to Swiss hospitals with the primary diagnosis of a RSTS. The yearly number of RSTS patients and the incidence (1.91/100.000) stayed constant within these 11 years. There were five sarcoma centers. We saw a clear trend of RSTS patients being treated (especially surgically) in centers over the 11 years. The complication rate of surgical-treated patients was higher in sarcoma centers (55% vs. 40%), though the overall mortality rate was lower (3.2% vs. 9.1%)., Conclusion: Centralization of RSTS treatment to certified sarcoma centers leads to a lower overall mortality rate and thus is highly recommended., (© 2021. The Author(s).)

Background: Nearly half of HIV-related deaths occur in East and Southern Africa, yet data on causes of death (COD) are scarce. We determined COD and associated factors among people living with HIV (PLHIV) in rural Tanzania., Methods: PLHIV attending the Chronic Diseases Clinic of Ifakara, Morogoro are invited to enrol in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). Among adults (≥ 15 years) enrolled in 2005-2018, with follow-up through April 2019, we classified COD in comprehensive classes and as HIV- or non-HIV-related. In the subset of participants enrolled in 2013-2018 (when data were more complete), we assessed cause-specific mortality using cumulative incidences, and associated factors using proportional hazards models., Results: Among 9871 adults (65% female, 26% CD4 count < 100 cells/mm 3 ), 926 (9%) died, among whom COD were available for 474 (51%), with missing COD mainly in earlier years. The most common COD were tuberculosis (N = 127, 27%), non-AIDS-related infections (N = 72, 15%), and other AIDS-related infections (N = 59, 12%). Cardiovascular and renal deaths emerged as important COD in later calendar years, with 27% of deaths in 2018 attributable to cardiovascular causes. Most deaths (51%) occurred within the first six months following enrolment. Among 3956 participants enrolled in 2013-2018 (N = 203 deaths, 200 with COD ascertained), tuberculosis persisted as the most common COD (25%), but substantial proportions of deaths from six months after enrolment onwards were attributable to renal (14%), non-AIDS-related infections (13%), other AIDS-related infections (10%) and cardiovascular (10%) causes. Factors associated with higher HIV-related mortality were sex, younger age, living in Ifakara town, HIV status disclosure, hospitalisation, not being underweight, lower CD4 count, advanced WHO stage, and gaps in care. Factors associated with higher non-HIV-related mortality included not having an HIV-positive partner, lower CD4 count, advanced WHO stage, and gaps in care., Conclusion: Incidence of HIV-related mortality was higher than that of non-HIV-related mortality, even in more recent years, likely due to late presentation. Tuberculosis was the leading specific COD identified, particularly soon after enrolment, while in later calendar years cardiovascular and renal causes emerged as important, emphasising the need for improved screening and management., (© 2022. The Author(s).)

Objective: Ritonavir-boosted protease inhibitors (bPI) in people living with HIV (PLWH) have been associated with renal impairment. Limited data are available from rural sub-Saharan Africa., Methods: Using data from the Kilombero and Ulanga Antiretroviral Cohort Study (KIULARCO) in rural Tanzania from 2005-01/2020, we assessed the prevalence of renal impairment (estimated glomerular filtration rate <60 mL/min/1.73m2) at the time of switch from first-line antiretroviral treatment (ART) to bPI-regimen and the incidence of renal impairment on bPI. We assessed risk factors for renal impairment using logistic and Cox regression models., Results: Renal impairment was present in 52/687 PLWH (7.6%) at the switch to bPI. Among 556 participants with normal kidney function at switch, 41 (7.4%) developed renal impairment after a median time of 3.5 (IQR 1.6-5.1) years (incidence 22/1,000 person-years (95%CI 16.1-29.8)). Factors associated with renal impairment at switch were older age (adjusted odds ratio (aOR) 1.55 per 10 years; 95%CI 1.15-2.11), body mass index (BMI) <18.5 kg/m2 (aOR 2.80 versus ≥18kg/m2; 95%CI 1.28-6.14) and arterial hypertension (aOR 2.33; 95%CI 1.03-5.28). The risk of renal impairment was lower with increased duration of ART use (aOR 0.78 per one-year increase; 95%CI 0.67-0.91). The renal impairment incidence under bPI was associated with older age (adjusted hazard ratio 2.01 per 10 years; 95%CI 1.46-2.78)., Conclusions: In PLWH in rural sub-Saharan Africa, prevalence and incidence of renal impairment among those who were switched from first-line to bPI-regimens were high. We found associations between renal impairment and older age, arterial hypertension, low BMI and time on ART., Competing Interests: The authors have declared that no competing interests exist.

Background: Community-based antiretroviral therapy (ART) dispensing by lay workers is an important differentiated service delivery model in sub-Sahara Africa. However, patients new in care are generally excluded from such models. Home-based same-day ART initiation is becoming widespread practice, but linkage to the clinic is challenging. The pragmatic VIBRA (Village-Based Refill of ART) trial compared ART refill by existing lay village health workers (VHWs) versus clinic-based refill after home-based same-day ART initiation., Methods and Findings: The VIBRA trial is a cluster-randomized open-label clinical superiority trial conducted in 249 rural villages in the catchment areas of 20 health facilities in 2 districts (Butha-Buthe and Mokhotlong) in Lesotho. In villages (clusters) randomized to the intervention arm, individuals found to be HIV-positive during a door-to-door HIV testing campaign were offered same-day ART initiation with the option of refill by VHWs. The trained VHWs dispensed drugs and scheduled clinic visits for viral load measurement at 6 and 12 months. In villages randomized to the control arm, participants were offered same-day ART initiation with clinic-based ART refill. The primary outcome was 12-month viral suppression. Secondary endpoints included linkage and 12-month engagement in care. Analyses were intention-to-treat. The trial was registered on ClinicalTrials.gov (NCT03630549). From 16 August 2018 until 28 May 2019, 118 individuals from 108 households in 57 clusters in the intervention arm, and 139 individuals from 130 households in 60 clusters in the control arm, were enrolled (150 [58%] female; median age 36 years [interquartile range 30-48]; 200 [78%] newly diagnosed). In the intervention arm, 48/118 (41%) opted for VHW refill. At 12 months, 46/118 (39%) participants in the intervention arm and 64/139 (46%) in the control arm achieved viral suppression (adjusted risk difference -0.07 [95% CI -0.20 to 0.06]; p = 0.256). Arms were similar in linkage (adjusted risk difference 0.03 [-0.10 to 0.16]; p = 0.630), but engagement in care was non-significantly lower in the intervention arm (adjusted risk difference -0.12 [-0.23 to 0.003]; p = 0.058). Seven and 0 deaths occurred in the intervention and control arm, respectively. Of the intervention participants who did not opt for drug refill from the VHW at enrollment, 41/70 (59%) mentioned trust or conflict issues as the primary reason. Study limitations include a rather small sample size, 9% missing viral load measurements in the primary endpoint window, the low uptake of the VHW refill option in the intervention arm, and substantial migration among the study population., Conclusions: The offer of village-based ART refill after same-day initiation led to similar outcomes as clinic-based refill. The intervention did not amplify the effect of home-based same-day ART initiation alone. The findings raise concerns about acceptance and safety of ART delivered by lay health workers after initiation in the community., Trial Registration: Registered with Clinicaltrials.gov (NCT03630549)., Competing Interests: The authors have declared that no competing interests exist.

Background: In cluster randomized trials (CRTs) or stepped wedge cluster randomized trials (SWCRTs) of malaria interventions, mosquito movement leads to contamination between trial arms unless buffer zones separate the clusters. Contamination can be accounted for in the analysis, yielding an estimate of the contamination range, the distance over which contamination measurably biases the effectiveness., Methods: A previously described analysis for CRTs is extended to SWCRTs and estimates of effectiveness are provided as a function of intervention coverage. The methods are applied to two SWCRTs of malaria interventions, the SolarMal trial on the impact of mass trapping of mosquitoes with odor-baited traps and the AvecNet trial on the effect of adding pyriproxyfen to long-lasting insecticidal nets., Results: For the SolarMal trial, the contamination range was estimated to be 146 m ([Formula: see text] credible interval [Formula: see text] km), together with a [Formula: see text] ([Formula: see text] credible interval [Formula: see text]) reduction of Plasmodium infection, compared to the [Formula: see text] reduction estimated without accounting for contamination. The estimated effectiveness had an approximately linear relationship with coverage. For the AvecNet trial, estimated contamination effects were minimal, with insufficient data from the cluster boundary regions to estimate the effectiveness as a function of coverage., Conclusions: The contamination range in these trials of malaria interventions is much less than the distances Anopheles mosquitoes can fly. An appropriate analysis makes buffer zones unnecessary, enabling the design of more cost-efficient trials. Estimation of the contamination range requires information from the cluster boundary regions and trials should be designed to collect this., (© 2021. The Author(s).)

Background: The extent to which drug-drug interactions (DDIs) between antiretrovirals (ARVs) and co-medications are recognized and managed has not been thoroughly evaluated in limited-resource settings., Objectives: This prospective questionnaire-based study aimed to determine the prevalence and risk factors for unrecognized/incorrectly managed DDIs in people living with HIV followed-up at the Chronic Diseases Clinic of Ifakara (CDCI) and enrolled in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO)., Methods: We prospectively included ARV-treated adults receiving ≥1 co-medication coming for a follow-up visit at the CDCI between March and July 2017. Using a structured questionnaire, physicians were requested to identify potentially clinically significant DDIs in the prescribed treatment, to provide recommendations for their management and to indicate any hurdles to implement the recommendations. Prescriptions were subsequently screened for DDIs using the Liverpool DDIs database. Identified clinically significant DDIs and their recommended management according to the DDIs database were compared with the information provided in the questionnaires., Results: Among 334 participants, the median age was 47 years (IQR = 40-56 years), 69% were female and 82% had ≥1 non-communicable disease (NCD). Overall, 129 participants had ≥1 clinically relevant DDI, which was not recognized and/or incorrectly managed in 56 participants (43%). Of those, 6 (11%) were due to limited monitoring options or medication affordability issues. In the multivariable logistic regression, the presence of ≥1 NCD was associated with an increased risk for unrecognized/incorrect DDI management (OR = 15.8; 95% CI = 1.8-139.6)., Conclusions: Recognition/appropriate management of DDIs is suboptimal, highlighting the need for educational programmes, pharmacovigilance activities and increased access to medications and monitoring options. This should become a focus of HIV programmes given the increasing burden of NCDs in sub-Saharan Africa., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In cluster randomized trials (CRTs) of interventions against malaria, mosquito movement between households ultimately leads to contamination between intervention and control arms, unless they are separated by wide buffer zones., Methods: This paper proposes a method for adjusting estimates of intervention effectiveness for contamination and for estimating a contamination range between intervention arms, the distance over which contamination measurably biases the estimate of effectiveness. A sigmoid function is fitted to malaria prevalence or incidence data as a function of the distance of households to the intervention boundary, stratified by intervention status and including a random effect for the clustering. The method is evaluated in a simulation study, corresponding to a range of rural settings with varying intervention effectiveness and contamination range, and applied to a CRT of insecticide treated nets in Ghana., Results: The simulations indicate that the method leads to approximately unbiased estimates of effectiveness. Precision decreases with increasing mosquito movement, but the contamination range is much smaller than the maximum distance traveled by mosquitoes. For the method to provide precise and approximately unbiased estimates, at least 50% of the households should be at distances greater than the estimated contamination range from the discordant intervention arm., Conclusions: A sigmoid approach provides an appropriate analysis for a CRT in the presence of contamination. Outcome data from boundary zones should not be discarded but used to provide estimates of the contamination range. This gives an alternative to "fried egg" designs, which use large clusters (increasing costs) and exclude buffer zones to avoid bias., (© 2021. The Author(s).)

Introduction: In the HOSENG trial (NCT03598686), the secondary distribution of oral self-tests for persons absent or refusing to test during a home-based HIV testing campaign in rural Lesotho resulted in an increase in testing coverage of 21% compared to a testing campaign without secondary distribution. This study aims to determine the per patient costs of both HOSENG trial arms. Method: We conducted a micro-costing study to estimate the cost of home-based HIV testing with (HOSENG intervention arm) and without (HOSENG control arm) secondary self-test distribution from a provider's perspective. A mixture of top-down and bottom-up costing was used. We estimated both the financial and economic per patient costs of each possible testing cascade scenario. The costs were adjusted to 2018 US$. Results: The overall provider cost for delivering the home-based HIV testing with secondary distribution was US$36,481 among the 4,174 persons enumerated and 3,094 eligible for testing in the intervention villages compared to US$28,620 for 3,642 persons enumerated and 2,727 eligible for testing in the control. The cost per person eligible for testing was US$11.79 in the intervention vs. US$10.50 in the control. This difference was mainly driven by the cost of distributed oral self-tests. The cost per person tested was, however, lower in intervention villages (US$15.70 vs. US$22.15) due to the higher testing coverage achieved through self-test distribution. The cost per person confirmed new HIV+ was US$889.79 in the intervention and US$753.17 in the control. Conclusion: During home-based HIV testing in Lesotho, the secondary distribution of self-tests for persons absent or refusing to test during the visit reduced the costs per person tested and thus presents a promising add-on for such campaigns. Trial Registration: https://ClinicalTrials.gov/, identifier: NCT03598686., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Amstutz, Matsela, Lejone, Kopo, Glass and Labhardt.)

Background: Since the advent of universal test-and-treat , more people living with human immunodeficiency virus (PLHIV) initiating antiretroviral therapy (ART) are asymptomatic with a preserved immune system. We explored the impact of asymptomatic status on adherence and clinical outcomes., Methods: PLHIV registered in the Swiss HIV Cohort Study (SHCS) between 2003 and 2018 were included. We defined asymptomatic as Centers for Disease Control and Prevention stage A within 30 days of starting ART, non-adherence as any self-reported missed doses and viral failure as two consecutive viral load>50 copies/mL after >24 weeks on ART. Using logistic regression models, we measured variables associated with asymptomatic status and adherence and Cox proportional hazard models to assess association between symptom status and viral failure., Results: Of 7131 PLHIV, 76% started ART when asymptomatic and 1478 (22%) experienced viral failure after a median of 1.9 years (interquartile range, 1.1-4.2). In multivariable models, asymptomatic PLHIV were more likely to be younger, men who have sex with men, better educated, have unprotected sex, have a HIV-positive partner, have a lower viral load, and have started ART more recently. Asymptomatic status was not associated with nonadherence (odds ratio, 1.03 [95% confidence interval {CI}, .93-1.15]). Asymptomatic PLHIV were at a decreased risk of viral failure (adjusted hazard ratio, 0.87 [95% CI, .76-1.00]) and less likely to develop resistance (14% vs 27%, P < .001) than symptomatic PLHIV., Conclusions: Despite concerns regarding lack of readiness, our study found no evidence of adherence issues or worse clinical outcomes in asymptomatic PLHIV starting ART., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Up to 50% of patients in intensive care units develop intraabdominal hypertension (IAH) in the course of medical treatment. If not detected on time and treated adequately, IAH may develop into an abdominal compartment syndrome (ACS) which is associated with a high mortality rate. Patients undergoing cardiac surgery are especially prone to develop ACS due to several risk factors including intraoperative hypothermia, fluid resuscitation and acidosis. We investigated patients who developed ACS after cardiac surgery and analyzed potential risk factors, treatment and outcome., Methods: From 2011 to 2016, patients with ACS after cardiac surgery requiring decompressive laparotomy were prospectively recorded. Patient characteristics, details on the cardiac surgery, mortality rate and type of treatment of the open abdomen were analyzed., Results: Incidence of ACS in cardiac surgery patients was 1.0% (n = 42/4128), with a mortality rate of 57%. Ejection fraction, Euroscore2 as well as the perfusion time are independent risk factors for the development of ACS. The outcome of patients with ACS was independent of elective versus emergency surgery, gender, age, BMI or ASA score. In the 18 surviving patients, fascial closure was achieved in 72% after a median of 9 days., Conclusion: Abdominal compartment syndrome is a rare but serious complication after cardiac surgery with a high mortality rate. Independent risk factors for ACS were identified. Negative pressure wound therapy seems to promote and allow early fascia closure of the abdomen and represents therefore a likely benefit for the patient.

Background: Iron deficiency anaemia is of major concern in low-income settings, especially for women of childbearing age. Oral iron substitution efficacy is limited by poor compliance and iron depletion severity. We aimed to assess the efficacy and safety of intravenous ferric carboxymaltose versus oral iron substitution following childbirth in women with iron deficiency anaemia in Tanzania., Methods: This parallel-group, open-label, randomised controlled phase 3 trial was done at Bagamoyo District Hospital and Mwananyamala Hospital, Tanzania. Eligible participants were close to delivery and had iron deficiency anaemia defined as a haemoglobin concentration of less than 110 g/L and a ferritin concentration of less than 50 μg/L measured within 14 days before childbirth. Participants were randomly assigned 1:1 to receive intravenous ferric carboxymaltose or oral iron, stratified by haemoglobin concentration and site. Intravenous ferric carboxymaltose was administered at a dose determined by the haemoglobin concentration and bodyweight (bodyweight 35 kg to <70 kg and haemoglobin ≥100 g/L: 1000 mg in one dose; bodyweight 35 kg to <70 kg and haemoglobin <100 g/L, or bodyweight ≥70 kg and haemoglobin ≥100 g/L: 1500 mg in two doses at least 7 days apart; bodyweight ≥70 kg and haemoglobin <100 g/L: 2000 mg in two doses at least 7 days apart). Oral iron treatment consisted of three dried ferrous sulphate tablets of 200 mg containing 60 mg of elementary iron and 5 mg of folic acid every morning. Oral treatment was to be taken for 3 months after haemoglobin normalisation. The primary outcome was haemoglobin normalisation (>115 g/L) at 6 weeks. Follow-up visits were at 6 weeks, and 3, 6, and 12 months. Analyses were done in the modified intention-to-treat population of participants who had a 6-week haemoglobin concentration result, using logistic and linear regression models for binary and continuous outcomes, adjusted for baseline haemoglobin concentration and site. This trial is registered with ClinicalTrials.gov, NCT02541708., Findings: Between Oct 8, 2015, and March 14, 2017, 533 individuals were screened and 230 were enrolled and randomly assigned to a study group (114 to intravenous iron, 116 to oral iron). At 6 weeks, 94 (82%) participants in the intravenous iron group and 92 (79%) in the oral iron group were assessed for the primary outcome. 75 (80%) participants in the intravenous iron group and 47 (51%) in the oral iron group had normalised haemoglobin (odds ratio 4·65, 95% CI 2·33-9·27). There were two mild to moderate infusion-related adverse events; and five serious adverse events (three in the intravenous iron group, two in the oral iron group), unrelated to the study medication., Interpretation: Intravenous iron substitution with ferric carboxymaltose was safe and yielded a better haemoglobin response than oral iron. To our knowledge, this is the first study to provide evidence of the benefits and safety of intravenous iron substitution in a low-income setting., Funding: Vifor Pharma, R Geigy-Stiftung, Freiwillige Akademische Gesellschaft, and Swiss Tropical and Public Health Institute., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Incomplete antiretroviral therapy (ART) adherence, even if sufficient to maintain viral suppression, is associated with enhanced inflammation in persons with HIV (PWH). However, its clinical implications remain unknown., Methods: PWH enrolled in the Swiss HIV Cohort Study without a history of cardiovascular disease (CVD) who initiated ART between 2003 and 2018 and had viral suppression (<50 copies/mL) for ≥6 months were evaluated. The association between incomplete self-reported ART adherence (≥1 or ≥2 missed doses in the last month) and (1) any CVD event (myocardial infarction, revascularization, cerebral hemorrhage, stroke, and/or death due to CVD event) or (2) non-CVD-related death was evaluated using adjusted Cox proportional hazards models., Results: A total of 6971 PWH (74% male) were included in the analysis (median age [interquartile range {IQR}], 39 [32-47] years). The median (IQR) follow-up was 8 (4-11) years, with 14 (8-23) adherence questionnaires collected per participant. In total, 205 (3%) participants experienced a CVD event, and 186 (3%) died a non-CVD-related death. In an adjusted competing risk model where missing data were imputed, missing ≥1 ART dose showed an increased, but not statistically significant, risk for CVD events (hazard ratio [HR], 1.23; 95% CI, 0.85-1.79; P  = .28). Non-CVD-related mortality showed a statistically significantly increased risk with missing ≥1 ART dose (HR, 1.44; 95% CI, 1.00-2.07; P  = .05) and missing ≥2 ART doses (HR, 2.21; 95% CI, 1.37-3.57; P  = .001)., Conclusions: Incomplete ART adherence was significantly associated with an increased risk for non-CVD-related mortality in PWH with virologic suppression. This highlights the potential role of nonadherence to ART as a driver of non-AIDS clinical outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Arterial hypertension is the most prevalent risk factor for cardiovascular disease in sub-Saharan Africa. Only a few and mostly small randomized trials have studied antihypertensive treatments in people of African descent living in sub-Saharan Africa., Methods: In this open-label, three-arm, parallel randomized controlled trial conducted at two rural hospitals in Lesotho and Tanzania, we compare the efficacy and cost-effectiveness of three antihypertensive treatment strategies among participants aged ≥ 18 years. The study includes patients with untreated uncomplicated arterial hypertension diagnosed by a standardized office blood pressure ≥ 140/90 mmHg. The trial encompasses a superiority comparison between a triple low-dose antihypertensive drug combination versus the current standard of care (monotherapy followed by dual treatment), as well as a non-inferiority comparison for a dual drug combination versus standard of care with optional dose titration after 4 and 8 weeks for participants not reaching the target blood pressure. The sample size is 1268 participants with parallel allocation and a randomization ratio of 2:1:2 for the dual, triple and control arms, respectively. The primary endpoint is the proportion of participants reaching a target blood pressure at 12 weeks of ≤ 130/80 mmHg and ≤ 140/90 mmHg among those aged < 65 years and ≥ 65 years, respectively. Clinical manifestations of end-organ damage and cost-effectiveness at 6 months are secondary endpoints., Discussion: This trial will help to identify the most effective and cost-effective treatment strategies for uncomplicated arterial hypertension among people of African descent living in rural sub-Saharan Africa and inform future clinical guidelines on antihypertensive management in the region., Trial Registration: Clinicaltrials.gov NCT04129840 . Registered on 17 October 2019 ( https://www.clinicaltrials.gov/ ).

Background: The CASCADE trial showed that compared with usual care (UC), offering same-day (SD) antiretroviral therapy (ART) during home-based human immunodeficiency virus testing improved engagement in care and viral suppression 12 months after diagnosis. However, questions remain regarding long-term outcomes and the risk of propagating drug resistance., Methods: After completion of the primary endpoint at 12 months, participants not in care in both arms were traced and encouraged to access care. At 24 months, the following outcomes were assessed in both arms: engagement in care, viral suppression, and reasons for nonengagement. Furthermore, we explored the acquisition of drug resistance mutations (DRMs) among SD arm nonlinkers., Results: At 24 months, 64% (88/137) in the SD arm vs 59% (81/137) in the UC arm were in care (absolute difference [AD], 5%; 95% confidence interval [CI], -6 to16; P = .38) and 57% (78/137) vs 54% (74/137) had documented viral suppression (AD, 3%; 95% CI, -9 to 15; P = .28). Among 36 participants alive and not in care at 24 months with ascertained status, the majority rejected contact with the health system or were unwilling to take ART. Among 8 interviewed SD arm nonlinkers, 6 had not initiated ART upon enrollment, and no acquired DRMs were detected. Two had taken the initial 30-day ART supply and acquired DRMs., Conclusions: SD ART resulted in higher rates of engagement in care and viral suppression at 12 months but not at 24 months. Leveling off between both arms was driven by linkage beyond 12 months in the UC arm. We did not observe compensatory long-term disengagement in the SD arm. These long-term results endorse SD ART initiation policies., Clinical Trials Registration: NCT02692027., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: In sub-Saharan Africa, home-based HIV testing is validated and accepted, but coverage is low because household members are often absent during home-based testing campaigns. We aimed to measure the effect of a secondary distribution of oral-fluid HIV self-tests on coverage during home-based testing in rural Lesotho., Methods: The Home-Based Self-Testing (HOSENG) trial was a cluster-randomised, non-blinded superiority trial in rural villages in the catchment area of 20 health facilities of two districts in Lesotho (Butha-Buthe and Mokhotlong). Eligible villages had a consenting village chief and at least one registered village health worker; eligible households had a consenting representative aged 18 years or older. The HOSENG trial provided a recruitment platform for the interlinked Village-Based Refill of Antiretroviral Therapy (VIBRA) trial. Villages were randomly assigned 1:1:1:1 with block sizes of four to one of four groups: VIBRA control and HOSENG control; VIBRA control and HOSENG intervention; VIBRA intervention and HOSENG control; and VIBRA intervention and HOSENG intervention. Randomisation was stratified by district, village size, and access to the nearest health facility. An independent statistician was responsible for the computer-generated randomisation list. In the intervention group, oral-fluid HIV self-tests were left for absent or declining household members (aged ≥12 years) during a home visit from the HIV testing campaign team. One present household member was trained on self-test use. Distributed self-tests were followed up by village health workers. In control village clusters, absent or declining household members were referred to the clinic for HIV testing. The primary outcome was HIV testing coverage among all household members aged 12 years or older within 120 days, defined as a confirmed HIV test result or known status, reported in testing registers at the health facilities or on the follow-up forms of the village health worker. Adjusted random-effects logistic regression with individuals as the unit of analysis was used. This trial is registered with ClinicalTrials.gov, NCT03598686., Findings: Between July 26, 2018, and Dec 12, 2018, 3091 consenting households with 7816 household members aged 12 years or older were enrolled and randomly assigned (intervention: 57 village clusters, 1620 households, 4174 household members; control: 49 village clusters, 1471 households, 3642 household members). In the control group, 38 (3%) of 1455 initially absent or declining household members tested at a clinic within 120 days. In the intervention group, 841 (53%) of 1601 initially absent or declining household members had a confirmed status within 120 days; 12 (1%) of 841 tested at the clinic and 829 (99%) used their self-test kit. This resulted in a testing coverage of 2201 (60%) of 3642 in the control group versus 3386 (81%) of 4174 in the intervention group (odds ratio 3·00 [95% CI 2·52-3·59]; p<0·0001)., Interpretation: Secondary distribution of oral-fluid HIV self-tests during home-based testing increases testing coverage substantially and thus presents a promising add-on during testing campaigns., Funding: Swiss National Science Foundation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Globally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART)., Methods: GIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to <19 years) living with HIV with a VL ≥400 copies/mL (c/mL) while taking first-line ART. Recruitment takes place at sites in Lesotho and Tanzania. Participants are randomised in a 1:1 allocation to a control arm receiving the standard of care (3 sessions of enhanced adherence counselling, a follow-up VL test, continuation of the same regimen upon viral resuppression or empiric selection of a new regimen upon sustained elevated viremia) and an intervention arm (GRT to inform onward treatment). The composite primary endpoint is the occurrence of any one or more of the following events during the 36 weeks of follow-up period: i) death due to any cause; ii) HIV- or ART-related hospital admission of ≥24 h duration; iii) new clinical World Health Organisation stage 4 event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis); and iv) no documented VL <50 c/mL at 36 weeks follow-up. Secondary and exploratory endpoints assess additional health-related outcomes, and a nested study will assess the cost-effectiveness of the intervention. Enrolment of a total of 276 participants is planned, with an interim analysis scheduled after the first 138 participants have completed follow-up., Discussion: This randomised clinical trial will assess if the availability of resistance testing improves clinical outcomes in children and adolescents with elevated viremia while taking ART., Trial Registration: This trial is registered with ClinicalTrials.gov ( NCT04233242 ; registered 18.01.2020). More information: www.givemove.org .

Background: Current World Health Organization (WHO) antiretroviral therapy (ART) guidelines define virologic failure as two consecutive viral load (VL) measurements ≥1,000 copies/mL, triggering empiric switch to next-line ART. This trial assessed if patients with sustained low-level HIV-1 viremia on first-line ART benefit from a switch to second-line treatment., Methods and Findings: This multicenter, parallel-group, open-label, superiority, randomized controlled trial enrolled patients on first-line ART containing non-nucleoside reverse transcriptase inhibitors (NNRTI) with two consecutive VLs ≥100 copies/mL, with the second VL between 100-999 copies/mL, from eight clinics in Lesotho. Consenting participants were randomly assigned (1:1), stratified by facility, demographic group, and baseline VL, to either switch to second-line ART (switch group) or continued first-line ART (control group; WHO guidelines). The primary endpoint was viral suppression (<50 copies/mL) at 36 weeks. Analyses were by intention to treat, using logistic regression models, adjusted for demographic group and baseline VL. Between August 1, 2017, and August 7, 2019, 137 individuals were screened, of whom 80 were eligible and randomly assigned to switch (n = 40) or control group (n = 40). The majority of participants were female (54 [68%]) with a median age of 42 y (interquartile range [IQR] 35-51), taking tenofovir disoproxil fumarate/lamivudine/efavirenz (49 [61%]) and on ART for a median of 5.9 y (IQR 3.3-8.6). At 36 weeks, 22/40 (55%) participants in the switch versus 10/40 (25%) in the control group achieved viral suppression (adjusted difference 29%, 95% CI 8%-50%, p = 0.009). The switch group had significantly higher probability of viral suppression across different VL thresholds (<20, <100, <200, <400, and <600 copies/mL) but not for <1,000 copies/mL. Thirty-four (85%) participants in switch group and 21 (53%) in control group experienced at least one adverse event (AE) (p = 0.002). No hospitalization or death or other serious adverse events were observed. Study limitations include a follow-up period too short to observe differences in clinical outcomes, missing values in CD4 cell counts due to national stockout of reagents during the study, and limited generalizability of findings to other than NNRTI-based first-line ART regimens., Conclusions: In this study, switching to second-line ART among patients with sustained low-level HIV-1 viremia resulted in a higher proportion of participants with viral suppression. These results endorse lowering the threshold for virologic failure in future WHO guidelines., Trial Registration: The trial is registered at ClinicalTrials.gov, NCT03088241., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Home-based HIV testing fails to reach high coverage among adolescents and young adults (AYA), mainly because they are often absent during the day of home-based testing. ADORE (ADolescent ORal tEsting) is a mixed-method nested study among AYA in rural Lesotho, measuring the effect of home-based secondary distribution of oral HIV self-tests (HIVST) on coverage, as well as exploring how AYA perceive this HIV self-testing model., Methods: ADORE study was nested in a cluster-randomized trial. In intervention village-clusters, oral HIVST were left for household members who were absent or declined testing during a testing campaign. One present household member was trained on HIVST use. Distributed HIVST were followed up by village health workers (VHW). In control clusters no self-tests were distributed. The quantitative outcome was testing coverage among AYA (age 12 to 24) within 120 days, defined as a confirmed HIV test result or known status, using adjusted random-effects logistic regression on the intention-to-treat population. Qualitatively, we conducted in-depth interviews among both AYA who used and did not use the distributed HIVST., Results: From July 2018 to December 2018, 49 and 57 villages with 1471 and 1620 consenting households and 1236 and 1445 AYA in the control and intervention arm, respectively, were enrolled. On the day of the home-visit, a testing coverage of 37% (461/1236) and 41% (596/1445) in the control and the intervention arm, respectively, were achieved. During the 120 days follow-up period, an additional 23 and 490 AYA in control and intervention clusters, respectively, knew their status. This resulted in a testing coverage of 484/1236 (39%) in the control versus 1086/1445 (75%) in the intervention arm (aOR 8.80 [95% CI 5.81 to 13.32]; p < 0.001). 21 interviews were performed. Personal assistance after the secondary distribution emerged as a key theme and VHWs were generally seen as a trusted cadre., Conclusions: Secondary distribution of HIVST for AYA absent or refusing to test during home-based testing in Lesotho resulted in an absolute 36% increase in coverage. Distribution should, however, go along with clear instructions on the use of the HIVST and a possibility to easily access more personal support., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: This study tested a theory-based adherence-enhancing intervention: the "Interprofessional Medication Adherence Program" (IMAP) to increase human immunodeficiency virus (HIV) retention in care., Methods: We retrospectively compared our intervention center (intervention group [IG]) with a standard of care center (control group [CG]) both participating in the Swiss HIV Cohort Study between 2004 and 2012. Endpoints were defined as >6-month and >12-month gaps in care for intervals of care longer than 6 and 12 months without any blood draw. Inverse probability of treatment weights was used to adjust for differences between patients at the 2 centers. Viral failure was defined as ribonucleic acid ≥50 copies/mL after 24+ weeks on antiretrovirals., Results: The IG included 451 patients, CG 311. In the IG, 179 (40%) patients took part in the IMAP for a median of 27 months (interquartile range, 12-45). Gaps in care of ≥6 months were significantly more likely to happen in the CG versus IG (74.6% vs 57%, P < .001). The median time until the first treatment gap was longer in the IG vs CG (120 vs 84 weeks, P < .001). Gaps in care of ≥12 months evaluated in 709 (93%) patients were significantly more likely to occur in the CG compared with the IG (22.6% vs 12.5%, P < .001). The rate of viral failure was significantly lower in the IG (8.3% vs 15.1%, P = .003)., Conclusions: This study, in a real-world setting, shows the effectiveness of the IMAP to reduce 6- and 12-month gaps in follow up among people with HIV. These results should be confirmed by studies in other settings., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)