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Objectives: CD34+ hematopoietic stem cell (HSC) enumeration, crucial for HSC transplantation, is performed by flow cytometry to guide clinical decisions. Variability in enumeration arises from biological factors, assay components, and technology. External quality assurance schemes (EQAS) train participants to minimize inter-laboratory variations. The goal is to estimate total error (TE) values for CD34 cell enumeration using state-of-the-art (SOTA) methods with EQA data and to define quality specifications by comparing TE using different cutoffs., Methods: A total of 3,994 results from 40 laboratories were collected over 11 years (2011-2022) as part of the IC-2 Stem Cells Scheme of the GECLID Program that includes absolute numbers of CD34 cells. The data were analyzed in two periods: 2011-2016 and 2017-2022. The TE value achieved by at least 60 %, 70 %, 80 %, and 90  % of laboratories was calculated across the two different periods and at various levels of CD34 cell counts: above 25, 25 to 15, and under 15 cells/μL., Results: A decrease in the SOTA-based TE for CD34 cell enumeration was observed in the most recent period in 2017-2021 compared with 2012-2016. A significant increase of P75 TE values in the low CD34 range (<15 cells/μL) levels was found (p<0.001)., Conclusions: Technical advancements contribute to the decrease TE over time. The TE of CD34 cell FC counts is measure-dependent, making it responsive to precision enhancement strategies. The TE measured by EQAS in this study may serve as a quality specification for implementing ISO 15189 standards in clinical laboratories for CD34 cell enumeration., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Abstract: This multicenter study sponsored by the GETH-TC investigates the incidence and predictors of early (first 100 days) and late cardiac events (CEs; ECEs and LCEs, respectively) after allo-HCT in patients with acute myeloid leukemia (AML) treated with anthracyclines, focusing on exploring the impact of PTCY on cardiac complications and the impact of CEs on OS and NRM. A total of 1020 patients with AML were included. PTCY was given to 450 (44.1%) adults. Overall, 94 (9.2) patients experienced CEs, with arrythmias, pericardial complications, and heart failure the most prevalent. ECEs occurred in 49 (4.8%) patients within a median of 13 days after allo-HCT, whereas LCEs were diagnosed in 45 (4.4%) patients within a median of 3.6 years after transplant. Using PTCY increased the risk for ECEs in multivariate analysis (hazard ratio [HR], 2.86; P = .007) but did not significantly affect the risk for LCEs (HR, 1.06; P = .892). The impact of variables on outcomes revealed was investigated using multivariate regression analyses and revealed that the diagnosis of CEs decreased the likelihood of OS (HR, 1.66; P = .005) and increased the likelihood of NRM (HR, 2.88; P < .001). Furthermore, despite using PTCY increased ECEs risk, its administration was beneficial for OS (HR, 0.71; P = .026). In conclusion, although the incidence of CEs was relatively low, it significantly affected mortality. Standard doses of PTCY increased ECE risk but were associated with improved OS. Therefore, protocols for preventing cardiac complications among these patients are needed., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

In this work our aim was to identify early biomarkers in plasma samples associated with mortality in children with perinatal HIV treated early in life, to potentially inform early intervention targeting this vulnerable group. 20/215 children (9.3%) with perinatal HIV, enrolled within 3 months of age died prematurely within the first year of the study, despite early ART initiation. Using a propensity score, we selected 40 alive study participants having similar clinical and virological records compared to the deceased group. 13 HIV unexposed (HU) healthy children were additionally used as controls. Baseline plasma samples were analyzed using a targeted proteomic approach, and to assess pathogen-associated and damage-associated molecular patterns (PAMPs, DAMPs) levels. Data from deceased participants were compared to both control groups, with multivariate logistic regression models used to evaluate the association between mortality and plasma proteins. We developed a machine learning model to predict mortality risk, finding that IL-6 and CXCL11 not only were higher in deceased children than Matched-children with HIV (p < 0.001 and p = 0.0034) but also predictive of mortality (accuracy of 77%); levels of PAMPs were higher in deceased children (p = 0.0016). Thus, measuring early inflammatory biomarkers, particularly IL-6, could help mortality risk prediction and potentially guide targeted interventions., (© 2024. The Author(s).)

This multicenter study investigates the incidence and predictors of cardiac events (CE) following allo-HCT with PTCY in 453 AML patients. CE occurred in 57 (12.3%) patients within a median of 52 days (IQR: 13-289), with day 100 and 5-year cumulative incidences of 7.7% and 13.5%. Early (first 100 days) and late CE occurred at rates of 7.7% and 4.8%. The most prevalent CE were heart failure (n = 18, 31.6%), pericardial complications (n = 16, 28.1%), and arrhythmia (n = 14, 24.6%). The proportions of patients older than 55 years (64.9% vs. 46.1%, P = 0.010), with hypertension (36.8% vs. 18.4%, P = 0.001) and dyslipidemia (28.1% vs. 11.1%, P = 0.001) were higher in patients with CE. Patients undergoing haplo-HCT trend to have more CE (68.4% vs. 56.8%, P = 0.083). The multivariate regression analysis revealed that only hypertension (HR 1.88, P = 0.036) and dyslipidemia (HR 2.20, P = 0.018) were predictors for CE, with no differences according to donor type (haplo-HCT vs. others: HR 1.33, P = 0.323). Among the 57 patients with CE, the mortality rate was 12.2%. Notably, the diagnosis of CE negatively impacted NRM (HR 2.57, P = 0.011) and OS (HR 1.80, P = 0.009), underscoring necessity of aggressively treating cardiovascular risk factors, and implementing post-transplant cardiac monitoring protocols to prevent these complications., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Evaluate the effect of three multimonth dispensing (3MMD) of antiretroviral therapy (ART) on HIV care retention in southern Mozambique., Design: Retrospective cohort study., Methods: We analyzed routine health data from people with HIV (PWH) aged 10 years old and older who started ART between January 2018 and March 2021. Individuals were followed until December 2021. Cox proportional-hazards models were used to compare attrition (lost to follow-up, death, and transfer out) between 3MMD and monthly ART dispensing. Results were stratified by time on ART before 3MMD enrolment: 'early enrollers' (<6 months on ART) and 'established enrollers' (≥6 months on ART), and age groups: adolescents and youth (AYLHIV) (10-24 years) and adults (≥25 years)., Results: We included 7378 PWH (25% AYLHIV, 75% adults), with 59% and 62% enrolled in 3MMD, respectively. Median follow-up time was 11.3 [interquartile range (IQR): 5.7-21.6] months for AYLHIV and 10.2 (IQR: 4.8-20.9) for adults. Attrition was lower in PWH enrolled in 3MMD compared with monthly ART dispensing, in both established (aHR AYLHIV = 0.65; 95% CI: 0.54-0.78 and aHR adults = 0.50; 95% confidence interval (CI): 0.44-0.56) and early enrollers (aHR AYLHIV = 0.70; 95% CI: 0.58-0.85 and aHR adults = 0.63; 95% CI: 0.57-0.70). Among individuals in 3MMD, male gender (aHR = 1.30; 95% CI: 1.18-1.44) and receiving care in a medium-volume/low-volume healthcare facility (aHR = 1.18; 95% CI: 1.03-1.34) increased attrition risk. Conversely, longer ART time before 3MMD enrolment (aHR = 0.93; 95% CI: 0.92-0.94 per 1 month increase) and age at least 45 years (aHR = 0.77, 95% CI: 0.67-0.89) reduced risk of attrition., Conclusion: 3MMD improves retention in care compared with monthly dispensing among established and early enrollers, although to a lesser extent among the latter., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Even with increasing access to rapid HIV diagnosis and early antiretroviral therapy (ART) initiation, infants living with HIV seem to have adverse outcomes. We assessed the probability of death, viral suppression, and other HIV-related events in the first three years of life among early-treated children with perinatally-acquired HIV in South Africa, Mozambique, and Mali., Methods: We enrolled a cohort of infants who initiated ART within the initial 6 months of life and within 3 months of diagnosis. These children were monitored 2, 6, 12 and 24 weeks after enrolment, followed by biannual check-ups up to 4 years after enrolment. We assessed the probability of death, viral load (VL) suppression, severe immunosuppression (according to WHO guidelines), and engagement in care using Kaplan-Meier plots, and hazard ratios for these outcomes using multivariable Cox regression models., Findings: Two hundred and fifteen infants were enrolled and monitored for a median of 34 months [IQR, 16.3; 44.1]. ART initiation occurred at a median of 34 days of age [IQR, 26.0; 73.0]. The probability of death at 1 year of ART was 10% (95% CI, 6-14), increased to 12% (95% CI, 8-17) at 2 and remained in 12% at 3 years. The main risk factor for HIV/AIDS-related mortality was baseline viral load [HR: 2.98 (95% CI, 1.25-7.12)]. Sixty-one of 146 (42%) children achieved sustained virological control below lower limit of detection for any ≥1 year period between enrolment and 4 years after enrolment. Viral suppression during follow-up was inversely associated with baseline viral load [Hazard Ratio (HR): 0.72 (95% CI, 0.58-0.89] and adverse maternal social events [HR: 0.26 (95% CI, 0.15-0.45)]. Adherence to ART was assessed as optimal in 81% of the visits. Female sex at birth, lower age at diagnosis and maternal adverse social life events were risk factors for low adherence [Odds ratio, OR 1.25 (95% CI, 1.00-1.56); 1.12 (95% CI, 1.01-1.27) and 2.52 (95% CI, 2.16-12.37), respectively]., Interpretation: Despite early ART, mortality remains high in infants. High baseline VL and adverse maternal social environment increased the risk of poor outcomes. Sustained supportive strategies are essential during and after pregnancy, to achieve better survival., Funding: Early Treated Perinatally HIV Infected Individuals: Improving Children's Actual Life (EPIICAL) is a research consortium funded by ViiV Healthcare and led by Penta Foundation. The funder was not involved in the analysis and interpretation of data, writing of the report, or the decision to submit the paper for publication. The corresponding authors had access to all data and take final responsibility for the decision to submit., Competing Interests: The following institutions, to which the author-researchers belong, received funding from the sponsor (Penta Foundation) to carry out this research, who in turn received a non-competitive grant from ViiV named Early Treated Perinatally HIV Infected Individuals: Improving Children's Actual Life (EPIICAL): Fundación de Investigación Biomédica Hospital 12 de Octubre, Stellenbosch University, University of the Witwatersrand, Africa Health Research Institute, Fundação Ariel Glaser contra o SIDA Pediátrico, Centro de Investigaçao em Saude de Manhiça, Instituto Nacional de Saúde, Bambino Gesù Children's Hospital, Ragon Institute of MGH, MIT, and Harvard, University College of London, Gianni Benzi Pharmacological Research Foundation, University of Miami, Centre Hospitalier Universitaire Gabriel Touré, ISGlobal, Columbia University Irving Medical Center, University of Rome “Tor Vergata”, Penta Foundation. The authors reported no other relationships/conditions/circumstances that present a potential conflict of interest for this research. Elisa López reported being a full employee of ViiV Healthcare since April 2023. Outside the submitted work, Tacilta Nhampossa reported a grant from EDCTP Career Development Fellowships. Proposal: TMA2017CDF-1927 (2019–2022). Sheila Fernández-Luis reported a grant from Secretariat of Universities and Research, Ministry of Enterprise and Knowledge of the Government of Catalonia and cofounded by European Social Fund. Paolo Palma reported a grant from NIH from 2020 to 2025 named PAVE, grant from NIH-NIAID (Targting HIV reservoirs in children with HIVIS-DNA and MVA-CMDR vaccines, and reported being the founder of Promiomics, a spin-off company of University Tor Vergata. Nicola Cotugno reported being the CRO and founder of Promiomics, a spin-off company of University Tor Vergata. Helena Rabie reported personal fees from ViiV community engagement meeting, personal fees from MSD Community engagement meeting., (© 2024 The Author(s).)

In Mozambique, targeted provider-initiated HIV testing and counselling (PITC) is recommended where universal PITC is not feasible, but its effectiveness depends on healthcare providers' training. This study aimed to evaluate the effect of a Ministry of Health training module in targeted PITC on the HIV positivity yield, and identify factors associated with a positive HIV test. We conducted a single-group pre-post study between November 2018 and November 2019 in the triage and emergency departments of four healthcare facilities in Manhiça District, a resource-constrained semi-rural area. It consisted of two two-month phases split by a one-week targeted PITC training module ("observation phases"). The HIV positivity yield of targeted PITC was estimated as the proportion of HIV-positive individuals among those recommended for HIV testing by the provider. Additionally, we extracted aggregated health information system data over the four months preceding and following the observation phases to compare yield in real-world conditions ("routine phases"). Logistic regression analysis from observation phase data was conducted to identify factors associated with a positive HIV test. Among the 7,102 participants in the pre- and post-training observation phases (58.5% and 41.5% respectively), 68% were women, and 96% were recruited at triage. In the routine phases with 33,261 individuals (45.8% pre, 54.2% post), 64% were women, and 84% were seen at triage. While HIV positivity yield between pre- and post-training observation phases was similar (10.9% (269/2470) and 11.1% (207/1865), respectively), we observed an increase in yield in the post-training routine phase for women in triage, rising from 4.8% (74/1553) to 7.3% (61/831) (Yield ratio = 1.54; 95%CI: 1.11-2.14). Age (25-49 years) (OR = 2.43; 95%CI: 1.37-4.33), working in industry/mining (OR = 4.94; 95%CI: 2.17-11.23), unawareness of partner's HIV status (OR = 2.50; 95%CI: 1.91-3.27), and visiting a healer (OR = 1.74; 95%CI: 1.03-2.93) were factors associated with a positive HIV test. Including these factors in the targeted PITC algorithm could have increased new HIV diagnoses by 2.6%. In conclusion, providing refresher training and adapting the current targeted PITC algorithm through further research can help reach undiagnosed PLHIV, treat all, and ultimately eliminate HIV, especially in resource-limited rural areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Saura-Lázaro 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.)

Objective: The Janus Kinase (JAK) 2 (V617F) mutation is the most frequently detected in myeloproliferative neoplasms (MPN). JAK2(V617F) mutation displays a pro-inflammatory phenotype that may be associated to a higher risk of immune mediated diseases (IMIDs), thromboembolic complications or other cancers. We aimed to evaluate the prevalence and main features of both rheumatic and non-rheumatic IMIDs in a cohort of MPNs patients with JAK2 (V617F) mutation., Methods: Study of all patients diagnosed with MPNs and JAK2 (V617F) mutation at a tertiary hospital in Northern Spain from 2004 to 2022. We focused on patients with rheumatic IMIDs to assess the time from IMIDs diagnosis to the detection of JAK2V617F mutation, the clinical course and severity of the disease, potential thrombotic complications, malignancies and therapeutic response., Results: 130 patients (73 men/57 women; mean age, 70.1 ± 14.5 years) were identified. Fifty-four (41.5 %) patients were diagnosed with at least one IMID. The prevalence of rheumatic IMIDs was 7.7 % (n = 10), including rheumatoid arthritis (n = 4), polymyalgia rheumatica (n = 3), Sjögren syndrome (n = 1), antiphospholipid syndrome (n = 1) and autoinflammatory syndrome with WDR1 mutation (n = 1). Thrombotic complications were observed in 4 of these 10 patients. The clinical course of the rheumatic IMID was mild in most cases and responded to conventional immunosuppressive therapy. One patient was successfully treated with Baricitinib, a JAK1/JAK2 inhibitor., Conclusions: A high prevalence of rheumatic IMIDs is observed in patients with MPNs and JAK2 (V617F) mutation. JAK inhibitors might be a targeted therapy option in these patients., Competing Interests: Declaration of Competing Interest Disclosures that might be interpreted as constituting of possible conflict(s) of interest for the study: Dr. R Blanco received grants/research supports from Abbvie, MSD, and Roche, and had consultation fees/participation in company sponsored speaker´s bureau from Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly, UCB and MSD. Dr C Álvarez-Reguera, Diana Prieto-Peña, A Herrero-Morant, L Sánchez-Bilbao, Ana Batlle-López, Sara Fernández-López have not declared financial disclosures., (Copyright © 2023. Published by Elsevier B.V.)

The geographical distribution of malaria and HIV infections widely overlap in sub-Saharan Africa, constituting a complex global health challenge. The interplay between both infections raises concerns about potential immunological, clinical, and therapeutic interactions. Both diseases have been reported to exacerbate the transmission of the other, including the possible vertical transmission of HIV in pregnant individuals with malaria. Co-infection also increases the risk of adverse outcomes such as severe malaria and death. In addition, interactions between antiretroviral and antimalarial drugs have been reported, potentially reducing the efficacy of these drugs. We review the current knowledge of the epidemiological, clinical, immunological, and therapeutic interactions of both infections. We focus on the latest available data and identify key knowledge gaps that should be addressed to guide policy makers in providing optimal HIV and malaria prevention, care, and treatment in vulnerable populations., Competing Interests: Declaration of interests AF-R, SF-L, and RG were partly supported by the European and Developing Countries Clinical Trials Partnership 2 programme (grant numbers RIA2016MC-1613-MAMAH [AF-R and RG], RIA2020S-3272 -MULTIPLY [AF-R], and RIA2019PD-2882-UNIVERSAL [SF-L]), which is supported by the European Union. AS-L was supported by the Severo Ochoa predoctoral fellowship from ISGlobal and the predoctoral fellowship from the Secretariat of Universities and Research (Ministry of Enterprise and Knowledge of the Government of Catalonia), cofunded by the European Social Fund. ISGlobal acknowledges support from grant CEX2018-000806-S funded by Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación/10.13039/501100011033, and support from the Generalitat de Catalunya through the Centres de Recerca de Catalunya Program. Editorial note: The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Non-disclosure of known HIV status by people living with HIV but undergoing HIV testing leads to waste of HIV testing resources and distortion of estimates of HIV indicators. In Mozambique, an estimated one-third of persons who tested positive already knew their HIV-positive status. To our knowledge, this study is the first to assess the factors that prevent people living with HIV (PLHIV) from disclosing their HIV-positive status to healthcare providers during a provider-initiated counseling and testing (PICT) campaign., Methods: This analysis was nested in a larger PICT cross-sectional study performed in the Manhiça District, Southern Mozambique from January to July 2019, in which healthcare providers actively asked patients about their HIV-status. Patients who tested positive for HIV were crosschecked with the hospital database to identify those who had previously tested positive and were currently or previously enrolled in care. PLHIV who did not disclose their HIV-positive status were invited to participate and provide consent, and were interviewed using a questionnaire designed to explore barriers, patterns of community/family disclosure, and stigma and discrimination., Results: We found that 16.1% of participants who tested positive during a PICT session already knew their HIV-positive status but did not disclose it to the healthcare provider. All the participants reported previous mistreatment by general healthcare providers as a reason for nondisclosure during PICT. Other reasons included the desire to know if they were cured (33.3%) or to re-engage in care (23.5%). Among respondents, 83.9% reported having disclosed their HIV-status within their close community, 48.1% reported being victims of verbal or physical discrimination following their HIV diagnosis, and 46.7% reported that their HIV status affected their daily activities., Conclusion: Previous mistreatment by healthcare workers was the main barrier to disclosing HIV-positive status. The high proportion of those disclosing their HIV status to their community but not to healthcare providers suggests that challenges with patient-provider relationships affect this care behavior rather than social stigma and discrimination. Improving patient-provider relationships could increase trust in healthcare providers, reduce non-disclosures, and help optimize resources and provide accurate estimates of the UNAIDS first 95 goal., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Obtaining rapid and accurate HIV incidence estimates is challenging because of the need for long-term follow-up for a large cohort. We estimated HIV incidence among women who recently delivered in southern Mozambique by leveraging data available in routine health cards. A cross-sectional household HIV-testing survey was conducted from October 2017 to April 2018 among mothers of children born in the previous four years in the Manhiça Health Demographic Surveillance System area. Randomly-selected mother-child pairs were invited to participate and asked to present documentation of their last HIV test result. HIV-testing was offered to mothers with no prior HIV-testing history, or with negative HIV results obtained over three months ago. HIV incidence was estimated as the number of mothers newly diagnosed with HIV per total person-years, among mothers with a prior documented HIV-negative test. Among 5000 mother-child pairs randomly selected, 3069 were interviewed, and 2221 reported a previous HIV-negative test. From this group, we included 1714 mothers who had taken a new HIV test during the survey. Most of mothers included (83.3%,1428/1714) had a previous documented HIV test result and date. Median time from last test to survey was 15.5 months (IQR:8.0-25.9). A total of 57 new HIV infections were detected over 2530.27 person-years of follow-up. The estimated HIV incidence was 2.25 (95% CI: 1.74-2.92) per 100 person-years. Estimating HIV incidence among women who recently delivered using a community HIV-focused survey coupled with previous HIV-testing history based on patients' clinical documents is an achievable strategy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The Hospital at Home (HaH) model has been positioned as an appropriate therapeutic strategy for selected patients undergoing autologous hematopoietic stem cell transplantation (ASCT). This care model provides hospital-equivalent care, in terms of both quality and quantity, with medical and nursing staff that go to the patient's home. Here we describe our experience with a full HaH model for patients undergoing ASCT during the phase of aplasia. The patients met the eligibility criteria between January 1997 and December 2019 and were discharged from the hospital and admitted into the HaH-ASCT program on the same day they in which hematopoietic stem cells were infused. A total of 84 patients were included. The median patient age was 54 years (range, 16 to 74 years), and the median duration of participation in the HaH program was 17 days (range, 3 to 86 days). Only 10 of these patients (12%) required hospital readmission to the hematology department, 9 of them due to sepsis and 1 because of family care support claudication. Seventy-two patients (86%) experienced an episode of neutropenic fever during the HAH admission, with a median duration of 2 days (interquartile range [IQR], 1 to 11 days); all were treated with empiric i.v. antimicrobial therapy. Most patients (88%) presented with mucositis (44% with grade 3-4). Parenteral nutrition was administered in 26% of patients for a median of 6 days (IQR, 1 to 12 days). Most patients (94%) required at least 1 blood product transfusion at home. There was no transplantation-related mortality during the HaH-ASCT program or in the patients who were readmitted. With careful selection of patients and a comprehensive and well- experienced multidisciplinary team (doctors, nurses, and auxiliary nurses) in the HaH department and in close collaboration with the hematology department, complete at-home management of ASCT recipients immediately after transplantation is possible. This allows patients undergoing an aggressive procedure such as ASCT to remain in their own familiar environment, providing a better quality of life with a program that has demonstrated to be effective and safe, with a low incidence of complications and no associated mortality., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Logistic regression (LR) is the most common prediction model in medicine. In recent years, supervised machine learning (ML) methods have gained popularity. However, there are many concerns about ML utility for small sample sizes. In this study, we aim to compare the performance of 7 algorithms in the prediction of 1-year mortality and clinical progression to AIDS in a small cohort of infants living with HIV from South Africa and Mozambique. The data set (n = 100) was randomly split into 70% training and 30% validation set. Seven algorithms (LR, Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Naïve Bayes (NB), Artificial Neural Network (ANN), and Elastic Net) were compared. The variables included as predictors were the same across the models including sociodemographic, virologic, immunologic, and maternal status features. For each of the models, a parameter tuning was performed to select the best-performing hyperparameters using 5 times repeated 10-fold cross-validation. A confusion-matrix was built to assess their accuracy, sensitivity, and specificity. RF ranked as the best algorithm in terms of accuracy (82,8%), sensitivity (78%), and AUC (0,73). Regarding specificity and sensitivity, RF showed better performance than the other algorithms in the external validation and the highest AUC. LR showed lower performance compared with RF, SVM, or KNN. The outcome of children living with perinatally acquired HIV can be predicted with considerable accuracy using ML algorithms. Better models would benefit less specialized staff in limited resources countries to improve prompt referral in case of high-risk clinical progression., Competing Interests: The authors have declared that no competing interests exist.

Objective: World Health Organization recommends promoting breastfeeding without restricting its duration among HIV-positive women on lifelong antiretroviral treatment (ART). There is little data on breastfeeding duration and mother to child transmission (MTCT) beyond 24 months. We compared the duration of breastfeeding in HIV-exposed and HIV-unexposed children and we identified factors associated with postpartum-MTCT in a semi-rural population of Mozambique., Methods: This cross-sectional assessment was conducted from October-2017 to April-2018. Mothers who had given birth within the previous 48-months in the Manhiça district were randomly selected to be surveyed and to receive an HIV-test along with their children. Postpartum MTCT was defined as children with an initial HIV positive result beyond 6 weeks of life who initiated breastfeeding if they had a first negative PCR result during the first 6 weeks of life or whose mother had an estimated date of infection after the child's birth. Cumulative incidence accounting for right-censoring was used to compare breastfeeding duration in HIV-exposed and unexposed children. Fine-Gray regression was used to assess factors associated with postpartum-MTCT., Results: Among the 5000 mother-child pairs selected, 69.7% (3486/5000) were located and enrolled. Among those, 27.7% (967/3486) children were HIV-exposed, 62.2% (2169/3486) were HIV-unexposed and for 10.0% (350/3486) HIV-exposure was unknown. Median duration of breastfeeding was 13.0 (95%CI:12.0-14.0) and 20.0 (95%CI:19.0-20.0) months among HIV-exposed and HIV-unexposed children, respectively (p<0.001). Of the 967 HIV-exposed children, 5.3% (51/967) were HIV-positive at the time of the survey. We estimated that 27.5% (14/51) of the MTCT occurred during pregnancy and delivery, 49.0% (2551) postpartum-MTCT and the period of MTCT remained unknown for 23.5% (12/51) of children. In multivariable analysis, mothers' ART initiation after the date of childbirth was associated (aSHR:9.39 [95%CI:1.75-50.31], p = 0.001), however breastfeeding duration was not associated with postpartum-MTCT (aSHR:0.99 [95%CI:0.96-1.03], p = 0.707)., Conclusion: The risk for postpartum MTCT was nearly tenfold higher in women newly diagnosed and/or initiating ART postpartum. This highlights the importance of sustained HIV screening and prompt ART initiation in postpartum women in Sub-Saharan African countries. Under conditions where HIV-exposed infants born to mothers on ART receive adequate PMTCT, extending breastfeeding duration may be recommended., Competing Interests: The authors have declared that no competing interests exist.

Background: The World Health Organization (WHO) risk assessment algorithm for vertical transmission of HIV (VT) assumes the availability of maternal viral load (VL) result at delivery and early viral control 4 weeks after initiating antiretroviral treatment (ART). However, in many low-and-middle-income countries, VL is often unavailable and mothers' ART adherence may be suboptimal. We evaluate the inclusion of the mothers' self-reported adherence into the established WHO-algorithm to identify infants eligible for enhanced post-natal prophylaxis when mothers' VL result is not available at delivery., Methods: We used data from infants with perinatal HIV infection and their mothers enrolled from May-2018 to May-2020 in Mozambique, South Africa, and Mali. We retrospectively compared the performance of the WHO-algorithm with a modified algorithm which included mothers' adherence as an additional factor. Infants were considered at high risk if born from mothers without a VL result in the 4 weeks before delivery and with adherence <90%., Results: At delivery, 143/184(78%) women with HIV knew their status and were on ART. Only 17(12%) obtained a VL result within 4 weeks before delivery, and 13/17(76%) of them had VL ≥1000 copies/ml. From 126 women on ART without a recent VL result, 99(79%) had been on ART for over 4 weeks. 45/99(45%) women reported suboptimal (< 90%) adherence. A total of 81/184(44%) infants were classified as high risk of VT as per the WHO-algorithm. The modified algorithm including self-adherence disclosure identified 126/184(68%) high risk infants., Conclusions: In the absence of a VL result, mothers' self-reported adherence at delivery increases the number of identified infants eligible to receive enhanced post-natal prophylaxis., (© 2022. The Author(s).)

Introduction: Manhiça District, in Southern Mozambique harbors high HIV prevalence and a long history of migration. To optimize HIV care, we sought to assess how caregiver's mobility impacts children living with HIV (CLHIV)´s continuation in HIV care and to explore the strategies used by caregivers to maintain their CLHIV on antiretroviral treatment (ART)., Methods: A clinic-based cross-sectional survey conducted at the Manhiça District Hospital between December-2017 and February-2018. We enrolled CLHIV with a self-identified migrant caregiver (moved outside of Manhiça District ≤12 months prior to survey) and non-migrant caregiver, matched by the child age and sex. Survey data were linked to CLHIV clinical records from the HIV care and treatment program., Results: Among the 975 CLHIV screened, 285 (29.2%) were excluded due to absence of an adult at the appointment. A total of 232 CLHIV-caregiver pairs were included. Of the 41 (35%) CLHIV migrating with their caregivers, 38 (92.6%) had access to ART at the destination because either the caregivers travelled with it 24 (63%) or it was sent by a family member 14 (36%). Among the 76 (65%) CLHIV who did not migrate with their caregivers, for the purpose of pharmacy visits, 39% were cared by their grandfather/grandmother, 28% by an aunt/uncle and 16% by an adult brother/sister. CLHIV of migrant caregivers had a non-statistically significant increase in the number of previous reported sickness episodes (OR = 1.38, 95%CI: 0.79-2.42; p = 0.257), ART interruptions (OR = 1.73; 95%CI: 0.82-3.63; p = 0.142) and lost-to-follow-up episodes (OR = 1.53; 95%CI: 0.80-2.94; p = 0.193)., Conclusions: Nearly one third of the children attend their HIV care appointments unaccompanied by an adult. The caregiver mobility was not found to significantly affect child's retention on ART. Migrant caregivers adopted strategies such as the transportation of ART to the mobility destination to avoid impact of mobility on the child's HIV care. However this may have implications on ART stability and effectiveness that should be investigated in rural areas., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Retention in HIV care is a challenge in Mozambique. Mozambique´s southern provinces have the highest mobility levels of the country. Mobility may result in poorer response to HIV care and treatment initiatives., Methods: We conducted a cross-sectional survey to explore the impact of mobility on retention for HIV-positive adults on ART presenting to the clinic in December 2017 and January 2018. Survey data were linked to participant clinical records from the HIV care and treatment program. This study took place in Manhiça District, southern Mozambique. We enrolled self-identified migrants (moved outside of Manhiça District ≤12 months prior to survey) and non-migrants, matched by age and sex., Results: 390 HIV-positive adults were included. We found frequent movement: 45% of migrants reported leaving the district 3-5 times over the past 12 months, usually for extended stays. South Africa was the most common destination (71%). Overall, 30% of participants had at least one delay (15-60 days) in ART pick-up and 11% were delayed >60 days, though no significant difference was seen between mobile and non-mobile cohorts. Few migrants accessed care while traveling., Conclusion: Our population of mobile and non-mobile participants showed frequent lapses in ART pick-up. Mobility could be for extended time periods and HIV care frequently did not continue at the destination. Studies are needed to evaluate the impact of Mozambique´s approach of providing 3-months ART among mobile populations and barriers to care while traveling, as is better education on how and where to access care when traveling., Competing Interests: The authors have declared that no competing interests exist.

Background: Eliminating mother-to-child HIV-transmission (EMTCT) implies a case rate target of new pediatric HIV-infections< 50/100,000 live-births and a transmission rate < 5%. We assessed these indicators at community-level in Mozambique, where MTCT is the second highest globally.., Methods: A cross-sectional household survey was conducted within the Manhiça Health Demographic Surveillance System in Mozambique (October 2017-April 2018). Live births in the previous 4 years were randomly selected, and mother/child HIV-status was ascertained through documentation or age-appropriate testing. Estimates on prevalence and transmission were adjusted by multiple imputation chained equation (MICE) for participants with missing HIV-status. Retrospective cumulative mortality rate and risk factors were estimate by Fine-Gray model., Results: Among 5000 selected mother-child pairs, 3486 consented participate. Community HIV-prevalence estimate in mothers after MICE adjustment was 37.6% (95%CI:35.8-39.4%). Estimates doubled in adolescents aged < 19 years (from 8.0 to 19.1%) and increased 1.5-times in mothers aged < 25 years. Overall adjusted vertical HIV-transmission at the time of the study were 4.4% (95% CI:3.1-5.7%) in HIV-exposed children (HEC). Pediatric case rate-infection was estimated at 1654/100,000 live-births. Testing coverage in HEC was close to 96.0%; however, only 69.1% of them were tested early(< 2 months of age). Cumulative child mortality rate was 41.6/1000 live-births. HIV-positive status and later birth order were significantly associated with death. Neonatal complications, HIV and pneumonia were main pediatric causes of death., Conclusions: In Mozambique, SPECTRUM modeling estimated 15% MTCT, higher than our district-level community-based estimates of MTCT among HIV-exposed children. Community-based subnational assessments of progress towards EMTCT are needed to complement clinic-based and modeling estimates.

Background: There are 170,000 children living with HIV in 2017 in Mozambique. Scaling-up HIV care requires effective retention along the cascade. We sought to evaluate the pediatric cascade in HIV care at the Manhiça District Hospital., Methods: A prospective cohort of children <15 years was followed from enrollment in HIV care (January 2013 to December 2015) until December 2016. Loss to follow-up (LTFU) was defined as not attending the HIV hospital visits for ≥90 days following last visit attended., Results: From the 438 children included {median age at enrollment in care of 3,6 [interquartile range (IQR): 1.1-8.6] years}, 335 (76%) were antiretroviral therapy (ART) eligible and among those, 263 (78%) started ART at enrollment in HIV care. A total of 362 children initiated ART during the study period and the incidence rate of LTFU at 12, 24, and 36 months post-ART initiation was 41 [95% confidence interval (CI): 34-50], 34 (95% CI: 29-41), and 31 (95% CI: 27-37) per 100 children-years, respectively. Median time to LTFU was 5.8 (IQR: 1.4-12.7) months. Children 5-9 years of age had a lower risk of LTFU compared with children <1 year [adjusted subhazard ratio 0.36 (95% CI: 0.20-0.61)]. Re-engagement in care (RIC) was observed in 25% of the LTFU children., Conclusions: The high LTFU found in this study highlights the special attention that should be given to younger children during the first 6 months post-ART initiation to prevent LTFU. Once LTFU, only a quarter of those children return to the health unit. Elucidating factors associated with RIC could help to fine tune interventions which promote RIC.

Introduction: Retention in care and reengagement of lost to follow-up (LTFU) patients are priority challenges in pediatric HIV care. We aimed to assess whether a telephone-call active tracing program facilitated reengagement in care (RIC) in the Manhiça District Hospital, Mozambique., Methods: Telephone tracing of LTFU children was performed from July 2016 to March 2017. Both ART (antiretroviral treatment) and preART patients were included in this study. LTFU was defined as not attending the clinic for ≥120 days after last attended visit. Reengagement was determined 3 months after an attempt to contact., Results: A total of 144 children initially identified as LTFU entered the active tracing program and 37 were reached by means of telephone tracing. RIC was 57% (95% CI, 39-72%) among children who could be reached versus 18% (95% CI, 11-26%) of those who could not be reached (p = 0.001)., Conclusion: Telephone tracing could be an effective tool for facilitating reengagement in pediatric HIV care. However, the difficulty of reaching patients is an obstacle that can undermine the program., (© The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Activation of pancreatic β-cell proliferation has been proposed as an approach to replace reduced functional β-cell mass in diabetes. Quiescent fibroblasts exit from G0 (quiescence) to G1 through pRb phosphorylation mediated by cyclin C/cdk3 complexes. Overexpression of cyclin D1, D2, D3, or cyclin E induces pancreatic β-cell proliferation. We hypothesized that cyclin C overexpression would induce β-cell proliferation through G0 exit, thus being a potential therapeutic target to recover functional β-cell mass. We used isolated rat and human islets transduced with adenovirus expressing cyclin C. We measured multiple markers of proliferation: [(3)H]thymidine incorporation, BrdU incorporation and staining, and Ki67 staining. Furthermore, we detected β-cell death by TUNEL, β-cell differentiation by RT-PCR, and β-cell function by glucose-stimulated insulin secretion. Interestingly, we have found that cyclin C increases rat and human β-cell proliferation. This augmented proliferation did not induce β-cell death, dedifferentiation, or dysfunction in rat or human islets. Our results indicate that cyclin C is a potential target for inducing β-cell regeneration., (Copyright © 2015 the American Physiological Society.)