Search Results (1,884)

The extraordinary genetic diversity of human immunodeficiency virus type 1 (HIV-1), driven by high mutation and recombination rates, poses significant challenges for diagnostics, therapy, and vaccine development. While variable regions enable immune escape, hyperconserved regions are critical for viral function and represent promising targets for novel therapeutic interventions. This study aimed to develop and validate a bioinformatic algorithm for quantitative assessment of sequence conservation and automated identification of functionally significant conserved regions across all major HIV-1 proteins. A total of 1119 full-length HIV-1 genome sequences representing major subtypes (A1, A2, A6, B, C, D, F1, F2, G, H, J, K) were analyzed. Normalized Shannon entropy (S-index) was calculated for each alignment column. Statistical thresholds for conserved regions were established using 95% confidence intervals derived from bootstrap resampling. Two complementary algorithms, clustering and local maxima detection, were applied to identify conserved regions, which were subsequently mapped to known functional domains based on literature data. Protein conservation varied markedly, with S_m values ranging from 0.784 (Vpu) to 0.920 (Pol). Gag, Pol, and Vpr demonstrated the highest overall conservation, while Env, Rev, Tat, and Vpu exhibited pronounced variability interspersed with conserved domains. In total, 25 conserved regions in Gag, 49 in Pol, 28 in Env, and 6–4 regions in accessory proteins (Vif, Vpr, Rev, Tat, Nef, Vpu) were identified. These regions corresponded to critical functional elements including enzyme catalytic centers, zinc fingers, receptor-binding sites, protein interaction interfaces, and membrane-anchoring domains. The developed computational framework enables statistically grounded identification of evolutionarily constrained regions across analyzed HIV-1 subtypes. The identified conserved regions represent candidate sites for further investigation and may inform downstream studies focused on antiviral target prioritization, immunogen design, and diagnostic assay development. However, their translational applicability requires additional analytical, structural, and experimental validation. Full article

Therapeutic vaccines are a key strategy to achieve the goal of “functional cure” of chronic viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human papillomavirus (HPV), and Epstein–Barr virus (EBV). Various platforms (such as viral vectors, nucleic acid vaccines, recombinant proteins, etc.) have successfully induced strong virus-specific T-cell responses in early trials, but their clinical efficacy is still limited by the immunosuppressive environment formed by the host. The core bottlenecks are severe T-cell exhaustion, viral immune escape, and various forms of local immune tolerance. Therefore, the field is moving toward combination therapies, including reduction of viral load, targeting of immune activation, and inhibition of inhibitory signaling pathways. This article summarizes the preclinical and clinical progress of therapeutic vaccines in the past decade, analyzes the major challenges in vaccine development, and discusses the future development directions in this field. Full article

Objective: Nutrition is critical for people living with human immunodeficiency virus (PLHIV); nonetheless, nutritional interventions have not been conducted among PLHIV in the Middle East and North Africa region. This study evaluated the effects of a nutrition-related education intervention on total knowledge, attitude, and practice (KAP) scores and on the intake of immune-enhancing foods and nutrients among PLHIV. Methods: Sixty-three PLHIV were recruited from an outpatient HIV clinic in Dubai, United Arab Emirates, between August and November 2023 and randomly assigned to an intervention (n = 31) or control group (n = 32). The intervention group participated in an individualized, six-session nutrition education program based on the Health Belief Model, whereas the control group received usual care plus a nutrition education brochure on HIV nutrition and health. Data were collected at baseline and after the five-month intervention period using validated instruments assessing HIV-related nutrition knowledge, attitudes, and practices. A food frequency questionnaire and two non-consecutive 24 h dietary recalls were used to assess the intake of immune-enhancing nutrients. Results: Post-intervention KAP score distributions differed significantly between the control and intervention groups for knowledge, attitude, and practices (p < 0.001, 0.003, and 0.001, respectively). Immune-enhancing vitamin intake did not differ significantly between groups, except vitamin E, which increased in the intervention group (p = 0.042). Conclusions: The intervention improved participants’ nutrition-related KAP scores but did not increase the intake of immune-enhancing nutrients, except for vitamin E. Further studies are warranted to develop interventions that improve the intake of immune-enhancing nutrients. Full article

Background and Clinical Significance: Human Herpesvirus 8-associated multicentric Castleman disease is a rare, lymphoproliferative disorder characterized by recurrent episodes of systemic inflammation. The disease is predominantly observed in human immunodeficiency virus-positive patients, but there is evidence of its occurrence in negative individuals. Its pathogenesis is driven by dysregulated cytokine activity, particularly interleukin 6. Additionally, these individuals have an increased risk of developing Kaposi Sarcoma, which may present simultaneously. Case Presentation: The current paper presents a case of a 58-year-old male patient admitted to the Hematology Department of the Emergency City Hospital in Timisoara, Romania, in October 2024, accusing fever, night sweats, palpitations, weight loss and general deterioration, approximately three months prior, with gradual progression. Clinical examination revealed bilateral lymphadenopathy in the cervical and inguinal regions. No cutaneous lesions were observed initially. Laboratory tests showed elevated inflammatory markers, pancytopenia, hypergammaglobulinemia and hyponatremia. HIV serology had negative results. CT imaging revealed extensive lymphadenopathy and splenomegaly. Further excisional biopsy of the inguinal and cervical lymphadenopathies was performed. Following the microscopic examination, the final diagnosis of Human Herpesvirus 8-associated multicentric Castleman disease concurrent with Kaposi Sarcoma was established. Conclusions: Human Herpesvirus 8-associated multicentric Castleman disease is predominantly observed in HIV-positive patients, but there is evidence of its occurrence in human immunodeficiency virus-negative individuals, presenting distinct epidemiological and pathological characteristics. Early and precise diagnosis is essential, as the disease can progress rapidly and may lead to severe or fatal outcomes. Full article

Tuberculosis remains one of the leading infectious causes of morbidity and mortality worldwide, disproportionately affecting women of reproductive age, particularly in low- and middle-income countries. Tuberculosis during pregnancy represents a major clinical challenge, as physiological and immunological changes associated with pregnancy may obscure symptoms, delay diagnosis, and contribute to adverse maternal and perinatal outcomes. This narrative review provides an updated and clinically oriented overview of tuberculosis during pregnancy, with particular emphasis on diagnostic challenges, imaging strategies, microbiological testing, maternal–fetal complications, and therapeutic management. Key topics include symptom-based screening, tuberculin skin test and interferon gamma release assays, as well as molecular diagnostic methods such as GeneXpert Mycobacterium tuberculosis/Rifampicin (MTB/RIF) and Xpert MTB/RIF Ultra, chest radiography, computed tomography, and emerging biomarkers. We also discuss the impact of tuberculosis on pregnancy outcomes, including prematurity, low birth weight, maternal morbidity, and neonatal complications, as well as the particular challenges posed by human immunodeficiency virus HIV coinfection and multidrug-resistant tuberculosis. Current treatment strategies, preventive approaches, postpartum care, neonatal management, and Bacille Calmette–Guérin vaccination are reviewed in light of contemporary evidence and international recommendations. Finally, we highlight practical diagnostic algorithms, current evidence gaps, and priorities for future research aimed at improving maternal and neonatal outcomes in both high- and low-resource settings. Full article

Background: The development of an efficacious preventive human immunodeficiency virus (HIV) vaccine remains a central goal of global HIV elimination efforts, yet biological performance alone will not determine a future vaccine’s public health impact. Method: This review draws on behavioral science, communication research, vaccine implementation, and HIV prevention literature to identify cognitive, social, and structural challenges that are likely to shape public acceptance and uptake of a future HIV vaccine, as well as to outline evidence-based opportunities for addressing them. Results: Based on the available literature, mental models of both HIV and vaccination will be a critical determinant of how communities consider a future vaccine, particularly given that emerging mRNA and adjuvanted platforms may generate side effects that could be easily misinterpreted and that highly effective long-acting pre-exposure prophylaxis (PrEP) options already exist and will shape how individuals evaluate a vaccine’s relative value. HIV-related stigma further complicates this landscape by making vaccination a socially interpreted behavior, unlike some other vaccination efforts. Together, these factors suggest that hesitancy and misalignment between public understanding and scientific evidence are predictable and should be anticipated rather than addressed reactively. At the same time, decades of HIV prevention implementation research have established an evidence base for vaccine communication, and existing community engagement infrastructure offers a foundation upon which future rollout efforts can build. We highlight three evidence-based strategies as particularly promising levers for encouraging acceptance and adoption. Conclusions: We conclude with recommendations for HIV vaccine researchers and healthcare professionals to invest in formative research, build community partnerships in advance of vaccine availability, and pilot integrated delivery models within existing HIV prevention services. Full article

As life expectancy for people living with human immunodeficiency virus (HIV) (PLWH) increases, long-term comorbidities, such as bone mineral density (BMD) loss, have emerged as significant clinical challenges. This study evaluated the prevalence and determinants of skeletal demineralization in a contemporary Romanian HIV cohort. A cross-sectional study was conducted among 180 PLWH (mean age 41.86 ± 12.69 years) undergoing stable antiretroviral therapy. Bone health was assessed via dual-energy X-ray absorptiometry (DXA), while body composition and metabolic status were evaluated using bioelectrical impedance analysis (BIA) and serum lipid profiling. A high prevalence of reduced skeletal mass (58.3%) was observed, with 10% of the cohort diagnosed with osteoporosis at a mean age of only 45.7 years. Significant correlations were identified between osteoporosis and a history of AIDS, active smoking, and hypertriglyceridemia. Notably, women with osteoporosis exhibited significantly lower current CD4+ T-cell counts (268.4 ± 180.5 cells/μL) compared to those with normal BMD. While the body mass index was an inconsistent predictor of bone health, BIA-derived bone mass effectively identified subclinical depletion. Our findings underscore a phenotype of premature skeletal aging in PLWH, driven by an interplay of immunological history, metabolic disturbances, and lifestyle factors. Early screening via DXA and BIA, alongside aggressive management of modifiable risks, is essential for mitigating fragility fractures in this aging population. Full article

Hepatitis B virus (HBV) remains a leading cause of chronic liver disease worldwide, contributing to cirrhosis and hepatocellular carcinoma. Sub-Saharan Africa accounts for an estimated 68% of incident HBV infections, where co-infection with human immunodeficiency virus (HIV) is common and associated with poorer clinical outcomes. In Botswana, limited HBV screening and the absence of established HBV management guidelines persist despite reported HIV-HBV co-infection rates ranging from 1.1% to 10.6%. This scoping review aimed to summarise existing research on HBV and HIV-HBV co-infection in Botswana and assess clinical and policy implications. Following PRISMA methodology, searches were conducted across PubMed, Google Scholar, Semantic Scholar, and Consensus databases. Thirty eligible peer-reviewed studies were identified and evaluated for prevalence data, virological characteristics, genotypes, mutations, treatment outcomes, vaccination programs, and the availability of guidelines. Findings indicate intermediate-to-high HBV and HIV-HBV disease burden, substantial occult HBV infection, and gaps in diagnostic and preventive practices. The lack of routine screening, deficient infant birth-dose and adult vaccination, and established treatment pathways likely increase the risk of HBV-associated morbidity and mortality. Strengthened public health interventions, including expanded testing, enhanced vaccination coverage, and prevention of mother-to-child transmission strategies, are recommended to improve disease control and clinical outcomes in Botswana. Full article

Adolescents and young people (AYP) experience a disproportionate burden of both mental health conditions and HIV, particularly in low- and middle-income countries (LMICs)-nations classified by the World Bank as having lower or middle economies. Mental health problems such as depression, anxiety, and substance use increase HIV (Human Immunodeficiency Virus that attacks the human immune system and leads to various illnesses when untreated) risk, and negatively affect treatment adherence and outcomes. However, mental health remains insufficiently integrated into HIV research and programming. Evidence on how mental health services are operationally integrated into HIV prevention and treatment for this population is limited and fragmented. This scoping review mapped existing evidence on the integration of mental health services into HIV treatment programs for AYP in LMICs, guided by PRISMA-ScR (a guideline used for reporting scoping reviews in research) and the Person–Concept–Context framework, a framework used to define specific research question in research. In this case, the population was adolescents and young people (10–24 years) receiving HIV prevention or treatment services, the concept referring to the integration of mental health interventions such as screening, assessment and counseling within HIV services, and the context focused on low- and middle-income countries (LMICs). PubMed, MEDLINE, Scopus and PsycINFO databases were searched for studies published between 2014 and 2024. Eligible studies reported mental health screening, assessment, treatment, or referral within HIV services for AYP in LMICs. Two reviewers independently screened studies, assessed full texts, and extracted data. Of 634 records identified, ten (10) studies met the inclusion criteria. All were conducted in Sub-Saharan Africa and primarily used qualitative or pilot designs. Four integration approaches were identified: routine mental health screening within HIV services, task-shifting to trained lay providers, peer-led and community-based psychosocial support, and culturally adapted, youth-centered psychological interventions. Common barriers included stigma, low mental health literacy, limited training and supervision, staffing constraints, and weak referral systems. Existing evidence is limited, remains exploratory, preliminary, and largely focused on feasibility and implementation experiences, suggesting that integrating mental health services within adolescent HIV care in LMICs may be feasible and acceptable when approaches are contextually adapted and participatory. Full article

Mining activities are characterised by a multiplicity of inherent occupational hazards. Exposure to mineral dust such as silica, asbestos, and coal dust is common in mining, leading to pneumoconiosis. Exposure to respirable silica-containing dust is one of the common respiratory hazards associated with adverse health effects such as silicosis, lung cancer, renal failure, scleroderma, systemic lupus erythematosus (SLE) and chronic obstructive pulmonary disease (COPD), to mention but just a few. In southern Africa, there is a rising epidemic of silicosis, human immunodeficiency virus (HIV) and tuberculosis (TB). Excessive exposure to silica-containing dust exacerbates the TB and silicosis epidemic in mining areas. There is poor control of dust exposure and a lack of occupational hygiene assessments of silica dust in mining in southern Africa. In southern Africa, there remains a persistent knowledge gap regarding the extent of occupational exposures to respirable chemical substances, such as silica dust. Consequently, occupational hygiene air monitoring was conducted in mining companies across four low-income Southern Africa Development Community (SADC) countries, Lesotho, Mozambique, Malawi and Zambia, to provide a baseline exposure dataset. The hazardous nature of work associated with mining activities still persists in these low-income countries, with 53% (n = 72) of quarries and 20% (n = 19) of coal mines having respirable quartz exposures exceeding the reference occupational exposure limit (OEL) of 0.1 milligrams per cubic meter (mg/m³). The highest exposure ranges for quartz were recorded in surface aggregate quarries, with the maximum concentration recorded at 2.739 mg/m³. The highest number of air samples (93%, n = 111), which were in compliance with the OEL of 3 mg/m³ for respirable dust, were recorded in the copper, diamond, ruby, cement quarry and gold mines. This exploratory study confirms the variable extent of mineworker exposure to respirable dust and corresponding quartz fractions emanating from different mining activities. The collected exposure data provides a baseline overview of exposures within the mining industry in the SADC region. It also serves as a vital input for future regional exposure surveillance databases, as well as preliminary data for directing future research towards regional exposure prevention initiatives. Full article

Background: Among the complications caused directly or indirectly by the Human Immunodeficiency Virus (HIV) are alterations in the auditory system. Children who are HIV-exposed but uninfected (HEU) appear to have a higher risk of hearing loss (HL) compared to their unexposed peers, but a lower risk than those infected with HIV. However, the literature remains inconclusive regarding this association. This study aims to evaluate the hearing function of HEU infants during the first months of life and to correlate these findings with maternal, gestational, and neonatal variables. Methods: This prospective cohort study included all HIV-exposed infants born in a quaternary hospital in southern Brazil between 2021 and 2023. Maternal, gestational, and neonatal data were collected, as well as the results of neonatal auditory screening. At approximately 6 months of age, otolaryngological and audiological assessments were performed, including wideband tympanometry and electrophysiological evaluation using Auditory Brainstem Response with frequency-specific stimuli. The prevalence of hearing loss refers to the number of infants affected. Results: Thirty-eight infants, with a mean age of 8 months (±3.3), completed the study. Of these, 1 (2.6%) presented with bilateral sensorineural HL, and 13 (34.2%) presented with conductive HL, with 6 cases being unilateral and 7 bilateral. No associations were found between hearing loss and maternal, gestational, or neonatal variables, except for maternal CD4 count, where higher CD4 cell counts were associated with an increased risk of conductive HL. Conclusion: The findings provide relevant data on auditory alterations in HEU infants, demonstrating a high prevalence of conductive HL. These results highlight the importance of monitoring the hearing of these children during the first years of life. Full article

Background/Objectives: Human immunodeficiency virus remains a significant public health challenge, with breastfeeding contributing to the risk of mother-to-child transmission. Although antiretroviral therapy significantly reduces this risk, obstetric nurses face complex challenges in translating evolving guidelines into clinical practice. This scoping review aims to map existing scientific evidence on obstetric nurses’ approaches to evidence-based practice regarding breastfeeding in the context of HIV. Methods: Following the Joanna Briggs Institute methodology and PRISMA-ScR guidelines, a search was conducted across PubMed, Scopus and EBSCOhost (MEDLINE Complete, CINAHL Complete, Cochrane Central Register of Controlled Trials, and Nursing & Allied Health Collection: Comprehensive) for studies published in English and Portuguese between 2015 and 2025. Studies were included if they focused on the role of obstetric nurses, nurse-midwives, or midwives in infant-feeding practices for women living with HIV. Results: Eight studies were included, predominantly from sub-Saharan Africa, with additional evidence from Europe and Canada. Findings reveal that infant-feeding counseling is shaped by a complex interplay of clinical protocols and personal beliefs. Significant gaps in knowledge translation were identified. While nurses demonstrate high technical confidence in lactation support, their distinct professional contribution is often obscured by research that aggregates all healthcare providers. Conclusions: The challenge of supporting breastfeeding in the context of HIV extends beyond technical protocol adherence. It points to persistent gaps in knowledge translation, variability in counselling practices, and the influence of contextual and professional factors on guideline implementation. Strengthening care requires sustained investment in profession-specific education, institutional support, and evidence-informed practice frameworks that enable obstetric nurses to exercise informed clinical judgement. Full article

Background: Long-acting drug delivery strategies could augment pediatric human immunodeficiency virus (HIV) treatment effectiveness by bypassing population-specific challenges such as adherence. We harnessed pharmacokinetic (PK) modeling to develop a biodegradable, subcutaneous (SQ), reservoir-style implant for HIV treatment in 2–5-year-old children. Methods: Plasma was collected from New Zealand White rabbits over 30 h after a single intravenous (IV) bolus of bictegravir (BIC, 0.75 mg/kg), islatravir (ISL, 5 mg/kg) and/or emtricitabine (FTC, 30 mg/kg) then over a year after subcutaneous insertion of two to three implants eluting these antiretrovirals. Plasma antiretrovirals were quantified by HPLC-MS/MS and population PK models were fit to the IV PK profile to derive a mean unit impulse response (UIR). UIR was used to numerically deconvolve SQ absorption rate from the implant PK profile. SQ dosing rates were translated to pediatric plasma concentrations using published clinical PK parameters. Results: BIC, FTC, and ISL PK profiles were best described by two-compartment models. Each implant achieved quantifiable plasma concentrations for >360 days. Median SQ absorption rates (μg/day) at 3, 6 and 12 months of implantation were 116, 98 and 71 for BIC; 116, 37 and 5 for ISL; and 236, 116 and 24 for FTC. These 6-month dosing rates translated to pediatric plasma concentrations of 24 ng/mL BIC, 0.14 ng/mL ISL, and 0.7 ng/mL FTC. Conclusions: Our novel long-acting delivery platform exhibited antiretroviral SQ dosing rates for ≥6 months that are anticipated to achieve plasma concentrations in children within an efficacious range warranting further development for pediatric HIV treatment. Full article

The prevalence of chronic conditions such as hypertension, diabetes, and Human Immunodeficiency Virus (HIV) is rising globally, yet access to continuous care remains limited, particularly in rural low- and middle-income countries. This study evaluated the acceptability and psychosocial predictors of retention in a linkage-to-care (LTC) intervention for patients with chronic conditions in rural South Africa. We conducted a cross-sectional analytical study with a retrospective cohort component among 1673 patients diagnosed with hypertension, diabetes, and/or HIV in Limpopo Province, South Africa. Acceptability and psychosocial factors were assessed cross-sectionally using a theory-informed, interviewer-administered questionnaire between January and June 2024. Retention in care over the preceding six months (July–December 2023) was extracted from routine clinic records and classified as consistent (no gaps > 6 months between visits) or inconsistent (≥1 gap > 6 months. Logistic regression examined associations between psychosocial factors and retention outcomes, adjusting for age, gender, marital status, and diagnostic category. Overall, 25.1% of participants maintained consistent retention over six months, while 74.9% were retained inconsistently. Acceptability of the LTC intervention varied significantly by diagnosis (p < 0.001): 79.5% of participants with multimorbidity rated the intervention as acceptable compared to 54.9% with hypertension, 64.5% with diabetes, and 46.8% with HIV. However, only 12.8% of multimorbid participants agreed that intervention activities fit well with their daily lives. In adjusted analyses, participants who were not happy to participate had 85% lower odds of consistent retention (adjusted odds ratio [AOR] = 0.15, 95% CI: 0.09–0.22) and 7.2 times higher odds of inconsistent retention (AOR = 7.2, 95% CI: 4.8–10.9). Most participants supported de-identified data sharing, though privacy concerns were elevated among those with multimorbidity. Acceptability of LTC interventions differs by diagnosis, with multimorbid patients reporting poorer alignment with daily routines. Retention is strongly associated with emotional engagement and self-efficacy, suggesting that LTC interventions should integrate psychosocial support and be contextually adapted for multimorbid patients in rural settings. Full article

Natural bioactive polysaccharides have been investigated for their ability to modulate antiviral immune responses. Polysaccharide peptide (PSP) from Coriolus versicolor previously restricted human immunodeficiency virus type 1 (HIV-1) entry into monocytic cells through a protein kinase R (PKR)-dependent cytoskeletal mechanism. However, its impact on antiviral signaling in adaptive cluster of differentiation 4 (CD4)+ T-cell models remains incompletely defined. Here, we evaluated concentration- and time-dependent effects of PSP (50–1000 µg/mL) in Jurkat T cells over 3 and 6 days. Cell viability was assessed by MTT, trypan blue exclusion, and viable cell density analysis. Immunoblotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were performed to examine Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), signal transducer and activator of transcription 1 and 2 (STAT1/STAT2), PKR, interferon gamma (IFN-γ), and cofilin-1 signaling. PSP did not induce cytotoxicity at any concentration. Instead, PSP promoted dose- and time-dependent upregulation of intracellular TLR4, PKR, phospho-PKR (Thr446), Cofilin-1, phospho-Cofilin-1 (Ser3), phospho-STAT1 (Tyr701), phospho-STAT2 (Tyr690), phospho-NF-κB (Ser536), and IFN-γ, with amplified responses at Day 6. These changes were paralleled by transcriptional induction of antiviral-associated genes. Collectively, PSP induces coordinated interferon (IFN)-associated and cytoskeletal regulatory signaling in Jurkat T cells without cytotoxicity, providing a mechanistic framework for future evaluation of viral permissiveness and antiviral responses in adaptive immune models. Full article