Search Results (92)

Infants born to HIV-positive mothers remain at significant risk of HIV acquisition despite maternal adherence to antiretroviral therapy, cesarean delivery, and formula feeding. Our previous study reported that initiating early antiretroviral treatment at three days post-SIV infection resulted in approximately eighty percent of pediatric virologic remission. In this study, we investigated treatment outcomes in postnatally SHIV-exposed infant macaques when early intervention was delayed by two days, as well as the mechanisms underlying virologic control. The results showed that, although initiating treatment at five days post-exposure effectively suppressed viral replication, only one of the three infant macaques achieved a sustained state of virologic remission following analytical treatment interruption. Notably, this virus-controlled infant lacked detectable virus-specific immunity, including neutralizing antibodies, cytotoxic T cell responses, and antibody-dependent cellular cytotoxicity. These findings highlight the critical importance of early treatment initiation as a key determinant of virologic control in HIV-exposed, infected infants. This study provides valuable insights for guiding early pediatric HIV intervention strategies in clinical settings. Full article

During 2022, AIDS claimed a life every minute and about 9.2 million HIV-infected people were not on treatment. In addition, a person living with HIV is estimated to be 20–30 times more susceptible to developing active tuberculosis. Every year, 130,000 infants are newly infected, with vertical transmission being the main cause of pediatric HIV infection. Thus, the development of an effective, safe, and accessible vaccine for neonates and/or adults is an urgent need to prevent or control HIV infection or progression to AIDS. An effective HIV vaccine should induce long-lasting mucosal immunity, broadly neutralizing antibodies, innate immunity, and robust stimulation of CD4+ and CD8+ T-cell responses. Recombinant BCG is a promising live-attenuated bacterial vaccine vector because of its capacity to stimulate T-cell immunity. As a slow-growing microorganism, it provides prolonged low-level antigenic exposure upon infecting macrophages and APCs, potentially stimulating both effector and memory T-cell responses. BCG is considered safe and is currently administered to 80% of infants in countries where it is part of the national immunization program. Additionally, BCG offers several benefits as a live vaccine vehicle since it is cost-effective, easy to mass-produce, and heat stable. It is also well-suited for newborns, as maternal antibodies do not interfere with its efficacy. Furthermore, BCG has a strong safety profile, having been administered to over three billion people as a TB vaccine. In this review, we provide an extensive summary of the literature relating to immunogenicity studies in animal models performed since 2011. Moreover, we provide a comprehensive analysis of the key factors influencing the design of recombinant BCG as a live vaccine vehicle: (i) expression vectors; (ii) selection of HIV immunogen; (iii) promoters to regulate gene expression; (iv) BCG strain and BCG codon optimization; (v) genetic plasmid stability; (vi) influence of preexisting immunity, route, and dose immunization; and (vii) safety profile. Full article

The human immunodeficiency virus (HIV-1) infiltrates the central nervous system (CNS) early in infection, leading to HIV-associated neurocognitive impairments, particularly pronounced in children who exhibit neurodevelopmental delay. Viral proteins, including the transactivator of transcription protein (Tat) and viral protein R (Vpr) are pivotal in HIV-1 neuropathogenesis, with their amino acid sequence variation influencing disease progression. Due to the difficulty of collecting cerebrospinal fluid from children, few studies have examined whether key Tat and Vpr neuropathogenic signatures found in blood are also present in the cerebrospinal fluid (CSF) of children with HIV. We employed Sanger sequencing for Tat and Vpr sequence analysis using retrospectively collected CSF samples from a South African pediatric HIV-1 subtype C cohort (n = 4). We compared our CSF-derived sequences with pediatric blood-derived sequences (n = 43) from various geographical regions, sourced from the Los Alamos database. Neuropathogenic amino acid variants were identified in Tat and Vpr sequences derived from CSF samples of South African pediatric participants No significant differences were found between subtype C sequences from CSF and blood. Regional analysis highlighted unique amino acid signatures. Obtaining pediatric CSF for HIV-1 sequencing is highly challenging. Despite a small sample size, this study offers rare insights into Tat and Vpr sequences in children, improving understanding of the potential HIV-1 brain pathogenesis in pediatric populations. Full article

(1) Background: Adolescents living with HIV (ALHIVs) experience significant challenges in adhering to treatment and remaining engaged in care as they transition from pediatric to adult HIV care programs. The aim of this qualitative evidence synthesis (QES) was to review qualitative studies that describe how ALHIVs experience transition practices in low- and middle-income countries. (2) Methods: The following databases were searched: PubMed, Wiley Library Online, EbscoHost (PsychARTICLES, MEDLINE, Scopus, CINAHL), the WHO database, Google Scholar, and reference mining of the included studies. The inclusion criteria were as follows: ALHIV 10–19 years old, interventions on the transition period or studies describing transition practices, published between 2012 and 2023, conducted in low- and middle-income countries, English language, and qualitative and mixed-method studies. This review adheres to the PRISMA guidelines. CASP and MMAT were used for methodological quality assessment, and GRADE CERQual was used for the confidence in review findings. (3) Results: Seven articles were included in the final review. The five overarching themes described: (1) transition readiness during the pre-transition phase; (2) structural (health systems) barriers and treatment literacy as challenges during the transition period; and (3) provided accounts of successful post-transition experiences and recommendations for improving the transition process (when these were not experienced as positive), while also describing the individual and collective contexts in which transition took place, as they outlined (4) individual (psychological) barriers and the facilitative role that (5) a supportive environment played in the outcome of the transition process. There was a high level of confidence in transition readiness, while the other themes were assessed as having moderate confidence due to methodological limitations and minor concerns about adequacy or relevance. (4) Conclusions: There is a dearth of qualitative studies on the transition experiences of ALHIVs and on how the transition process impacts adherence, retention in care, and mental well-being. We recommend the development of interventions in the form of a guided transition protocol to improve the transition experiences of ALHIVs. Full article

Febrile diseases such as malaria, typhoid fever, tuberculosis, and HIV/AIDS pose significant diagnostic challenges in Low- and Middle-Income Countries (LMICs). Misdiagnosis leads to delayed treatment, increased healthcare costs, and higher mortality rates. This study presents a prototype diagnostic framework integrating machine learning (ML) and explainable artificial intelligence (XAI) to enhance diagnostic performance, interpretability, and usability in resource-constrained settings. A dataset of 3914 patient records from secondary and tertiary healthcare facilities was used to train and validate predictive models, employing Random Forest, Extreme Gradient Boost, and Multi-Layer Perceptron with optimized hyperparameters. To ensure transparency, XAI techniques such as Local Interpretable Model-Agnostic Explanations (LIME) and Large Language Models (LLMs) were integrated, enabling clinicians to understand model predictions. A prototype mobile-based diagnostic system was developed to explore its feasibility for real-time decision-making. The system features an intuitive interface, patient record management, and AI-driven diagnostic insights with visual and textual explanations. While usability testing with simulated case studies demonstrated its potential, real-world deployment and large-scale clinical validation are yet to be conducted. The system is designed with scalability in mind, allowing for future adaptation to different LMIC settings. However, limitations such as dataset imbalance and exclusion of pediatric data remain. Future research will focus on refining the model, expanding the dataset, and conducting extensive clinical validation before real-world implementation. This study serves as a foundational step toward AI-driven diagnostic tools in resource-limited healthcare environments. Full article

Background: The MeMed BV^® BV score is a novel, promising host-protein score, differentiating bacterial from viral infections, that combines the expression levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP). The aim of our study was to determine its diagnostic accuracy in hospitalized febrile children. Methods: A prospective study was performed from December 2023 to April 2024 in two pediatric clinics at “Aghia Sophia” Children’s Hospital, Athens, Greece. Patients > 3 months old, presenting with fever, clinical suspicion of acute infection, and symptoms onset up to 7 days prior were considered eligible. Patients with cancer, Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Tuberculosis (TB), and immunodeficiency were excluded. Two pediatricians reviewed the clinical, laboratory, microbiological, and radiological data and assigned the final diagnosis. The experts were blinded to the BV scores. Results: One hundred and thirty-five patients were enrolled. The predominant medical condition was respiratory tract infection (59.3% lower, 26.7% upper). Twenty-nine (21.5%) patients were diagnosed with bacterial infections. The BV score demonstrated a sensitivity of 96.2%, specificity of 88.7%, and negative predictive value (NPV) of 98.9% for bacterial infections. Equivocal BV scores were reported in 8.9% of cases and were excluded from calculations. The area under the curve was 0.96 (95% CI: 0.93–0.99). A ROC curve analysis was performed, and the optimal cut-off score was estimated at 60, providing a sensitivity of 93.1%, specificity of 88.7%, and NPV of 97.9%. Conclusions: In our study population, the BV score showed high sensitivity and NPV in bacterial infection diagnosis. Further studies are needed to assess the possibility of replacing the “equivocal” range with a narrower one or a specific cut-off value. Full article

The study was conducted in all regions of Ethiopia, except Tigray. It describes types of Tuberculosis (TB) based on gender, age, region, HIV status, and geographic setting in Ethiopia. It is a cross-sectional study that utilized the Ministry of Health’s District Health Information System-based reporting to analyze all types of TB from July 2022 to March 2024. In total, 290,450 TB cases were detected: 42.6% (123,871) were female, 9.4% (27,160) were children (under 15 years of age), and 14.5% (42,228) were adolescents (10–19 years of age). About 48% (20,185) of adolescent TB cases were bacteriologically confirmed, of which 47.5% were females. Compared to children <5 years, the male-to-female ratio is 26% higher among older children (5–9 years of age) (Adjusted Odds Ratio (AOR): 1.26, 95% Confidence Interval (CI): 0.51–2.01)) and 53% higher among adolescents (AOR: 1.53, 95% CI 0.87–2.18). In short, about half of TB cases are infectious among older children and young adolescents of the female gender in Ethiopia. TB among these age categories may be addressed through the integration of TB services with reproductive health services and youth-friendly and pediatric clinics. Full article

Background: Lamivudine is widely used alone or in combination with other anti-HIV drugs in the infant to adolescent age groups of pediatric populations. Compounding of medications is frequently used for pediatric patients. However, many issues have been reported for the compounded formulation such as assay, stability, safety, and efficacy. Three-dimensional printing can overcome these issues. Objective: The aim of this study was to understand the effect of process and formulation variables on lamivudine printlets for pediatric populations using selective laser sintering. Methods: The Plackett–Burman screening design was used to prepare 12 formulations to study six variables, namely, laser scanning speed (130–150 °C), surface temperature (105–120 °C), chamber temperature (250–350 mm/s), sucrose (0–30%), hydroxypropyl methylcellulose (0–42%), and Kollidon^® CL-M (0–5%). The formulations were tested for dissolution, disintegration, hardness, assay, X-ray diffraction, differential scanning calorimetry, stability, and pharmacokinetics in Sprague Dawley rats. Results: The assay of the printlet formulations varied between 93.1 and 103.5% and the disintegration time was 2.8 ± 1.2 (F1) to 43.7 ± 2.7 (F10) s. Due to high surface temperatures, the unsintered powder in the printing chamber experienced significant changes in crystallinity. No statistical significance was observed between the pharmacokinetic parameters of the printlets and commercial tablets (p > 0.05). The maximum plasma concentration (C_max), time to reach maximum plasma concentration (T_max), and area under the curve (AUC) of the printlets and commercial tablets were 295.5 ± 33.0 and 305.0 ± 70.1 ng/mL, 0.5 ± 0.0 and 1.0 ± 0.8 h, and 1414.1 ± 174.0 and 1987.2 ± 700.5 ng.h/mL, respectively. Conclusions: In summary, fast-disintegrating and dissolving 3D printed lamivudine was found to be bioequivalent to commercial formulation of lamivudine. Thus, it is a viable method for dispensing personalized lamivudine printlets for pediatric populations. Full article

Background: Elite-neutralizer-derived HIV-1 envelopes (Envs), which induce broadly neutralizing antibodies (bnAbs), can inform HIV-1 vaccine design by serving as templates for bnAb-eliciting vaccines. Since single Env-based immunizations are insufficient to induce bnAb responses, sequential regimens using multivalent immunogens or Env cocktails hold greater promise. This underscores the need to develop stable Env trimers from diverse HIV-1 strains, particularly clade-C, which accounts for 50% of global infections and over 90% in India and South Africa. While various platforms exist to stabilize soluble Env trimers for use as antigenic baits and vaccines, stabilizing clade C trimers remains challenging. Methods: We stabilized an HIV-1 clade C trimer based on an Env isolated from a pediatric elite neutralizer (AIIMS_329) using multiple platforms, including SOSIP.v8.2, ferritin nanoparticles (NPs) and I53-50 two-component NPs, followed by characterization of their biophysical, antigenic, and immunogenic properties. Results: The stabilized 329 Envs showed binding to multiple HIV-1 bnAbs, with negligible binding to non-neutralizing antibodies. Negative-stain electron microscopy confirmed the native-like conformation of the Envs. Multimerization of 329 SOSIP.v8.2 on ferritin and two-component I53-50 NPs improved the affinity to HIV-1 bnAbs and showed higher immunogenicity in rabbits. Conclusions: The soluble 329 Env protein could serve as an antigenic bait, and multimeric 329 NP Envs are potential vaccine candidates. Full article

Background/Objectives: We aim to describe the changing inpatient epidemiology of NAFLD in the U.S. and identify major risk factors associated with mortality in the disease among hospitalized pediatric patients. Methods: Hospitalization data from the 1998–2020 National Inpatient Sample were utilized. ICD-9 and ICD-10 codes were used to identify pediatric patients (age less than 18 years old) with NAFLD, and risk factors for mortality were analyzed by logistic regression. Results: We identified 68,869 pediatric hospitalizations involving NAFLD. Among those, 970 (1.4%) died during hospitalization. Hospitalization rates have been rapidly increasing from 1998 to 2020 (incidence rate ratio (IRR): 1.07; 95% CI: 1.06–1.07; p < 0.001). There was a significant difference in mortality based on the type of hospital (rural, non-teaching urban, or teaching urban) in pediatric patients with NAFLD (p < 0.05). Coagulopathy was significantly associated with increased odds of mortality, while age ≥ 12 years, diabetes and obesity were associated with decreased odds of mortality (p < 0.05). Sex, race/ethnicity, hepatitis B, hepatitis C, HIV, and IV drug use were not significantly associated with mortality. Conclusions: Our study has shown ever increasing hospitalization rates for NAFLD in pediatric populations and well as significant risk factors associated with mortality. Further studies should be performed as more data on this patient population are collected. Full article

EPIICAL (Early treated Perinatally HIV-Infected individuals: Improving Children’s Actual Life) is a consortium of European and non-European research-driven organizations inter-connected with the aim of establishing a clinical and experimental platform for the early identification of novel therapeutic strategies for the pediatric Human Immunodeficiency Virus (HIV). Within the EPIICAL project, several pediatric clinical studies were conducted, requiring the collection and transfer of biological samples and associated data across boundaries within and outside Europe. To ensure compliance with the applicable rules on pediatric data and sample transfer and to support the efforts of academic partners, which may not always have the necessary expertise and resources in place for designing, managing and conducting multi-national studies, the consortium established a dedicated expert Working Group. This group has guided the consortium since the start of the project through the complexities of the ethical and regulatory aspects of international clinical studies. The group provided support in the design and preparation of the prospective and retrospective multi-center and multi-national pediatric studies with a focus on the clinical study protocols, informed consent and assent forms. In particular, well-structured informed consent and assent templates were developed, and data sharing and material transfer agreements were set up to regulate the transfer of samples among partners and sites. We considered that such support and the implementation of ad hoc agreements could provide effective practical solutions for addressing ethical and regulatory hurdles related to sharing data and transferring samples in international pediatric clinical research. Full article

Although every youth in pediatric/adolescent HIV care will need to transition to adult-oriented care, there are no existing evidence-based interventions to optimize health through this process. Healthcare transition poses a persistent challenge to the health of youth living with HIV, which may result in gaps in care engagement, medication adherence, and viral suppression. Our process evaluation of iTransition, a multilevel mobile health (mHealth) intervention, included iterative interviews with youth, providers, and Transition Champions. These data, along with team meeting notes, highlight the important role the intervention plays in addressing healthcare transition-related challenges, positioning it to fill a critical gap for both youth and providers. It also highlights important individual (e.g., competing priorities of youth and providers), clinical (e.g., electronic health record integration), and contextual (e.g., clinical policies during COVID-19 pandemic) challenges to intervention reach and implementation. More work is needed to refine interventions to support care continuity for youth living with HIV as they transition to adult-oriented care. Full article

Robust CD8⁺ T cell responses are critical for the control of HIV infection in both adults and children. Our understanding of the mechanisms driving these responses is based largely on studies of cells circulating in peripheral blood in adults, but the regulation of CD8⁺ T cell responses in tissue sites is poorly understood, particularly in pediatric infections. DNA methylation is an epigenetic modification that regulates gene transcription. Hypermethylated gene promoters are associated with transcriptional silencing and, conversely, hypomethylated promoters indicate gene activation. In this study, we evaluated DNA methylation signatures of CD8⁺ T cells isolated from several different anatomic compartments during pediatric AIDS-virus infection by utilizing the SIV_mac239/251 infected infant rhesus macaque model. We performed a stepwise methylation analysis starting with total cellular DNA, to immunomodulatory cytokine promoters, to specific CpG sites within the cytokine promoters in CD8⁺ T cells isolated from peripheral blood, lymph nodes, and intestinal tissue during the chronic phase of infection. Tissue-specific methylation patterns were determined for transcriptionally active promoters of key immunomodulatory cytokines: interferon gamma (IFNγ), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNFα). In this study, we observed tissue-specific differences in CD8⁺ T cell modulation by DNA methylation in SIV-infected infant macaques, highlighting the importance of evaluating cells from both blood and tissues to obtain a complete picture of CD8⁺ T cell regulation during pediatric HIV infection. Full article

This systematic review assessed the prevalence of transmitted and acquired HIV drug resistance (HIVDR) and the associated risk factors in Mozambique. A search of the PubMed, Cochrane, B-On, and Scopus databases up to December 2023 was conducted and included 11 studies with 1118 HIV-1 pol sequences. Drug resistance mutations (DRMs) to NNRTIs were found in 13% of the drug-naive individuals and 31% of those on ART, while NRTI resistance occurred in 5% and 10%, respectively. Dual-class resistance (NNRTI + NRTI) was detected in 2% of the drug-naive and 8% of ART-experienced individuals. DRMs to protease inhibitors (PIs) were found in 2% of the drug-naive and 5% of ART-experienced individuals. The rate of DRMs was significantly higher in Beira than in Maputo, as well as in pediatric patients than in adults and pregnant women. Subtype C predominated (94%) and was associated with lower viral loads and DRM rates as compared to the other subtypes. The high prevalence of DRMs, particularly to NNRTIs and NRTIs, highlights the need for ongoing surveillance and targeted interventions. These findings are critical for optimizing ART regimens and informing public health strategies in Mozambique, with particular attention to regions such as Beira and vulnerable populations such as pediatric patients. Full article

Background: There is limited evidence comparing hepatitis A seroprevalence among HIV-exposed uninfected (HEU), HIV-infected (HIV), and unexposed uninfected (HUU) children. This compromises rational vaccine decision-making. Methods: This study comprised a retrospective health facility-based population of children aged 1 month–12 years. Archival sera were tested for markers of acute (anti-HAV IgM) or past (total anti-HAV) HAV infection. Subgroup analysis was conducted based on perinatal HIV exposure or infection status. Results: Among 513 children, the median age was 10 (IQR: 4–25) months. The median maternal age was 29 (IQR: 25–34) years. An anti-HAV seropositivity of 95.1% (117/122 [95% CI 90.2–98.4]) was found among those ≤6 months of age, indicative of the rate of transplacental antibody transfer. Among 1–12-year-olds, hepatitis A seroprevalence was 19.3% (37/192 [95% CI 14.1–25.7]), while 1.1% (2/188 [95% CI 0.12–2.76]) had evidence of acute infection. Compared to HIV-exposed subgroups (HIV = 60%, 6/10 [95% CI 27.4–86.3] and HEU = 45%, 9/20 [95% CI 23.8–68]), hepatitis A seroprevalence among HUU children was low (29.2%, 47/161 [95% CI 22.4–37.0]). Conclusions: Natural immunity among HIV-exposed and unexposed children in South Africa is insufficient to protect against severe liver complications associated with HAV infection later in adulthood. Full article