Search Results (1,496)

People with HIV (PWH) experience higher rates of depression compared with the general population. Inflammation has been associated with depressive symptoms and may be associated with a subtype of depression, but the relationship between inflammation and depressive symptoms in PWH on antiretroviral therapy (ART) is unclear. In this study, inflammation biomarkers (IFN-γ, IL-1β, IL-6, IL-8, IL-12p70, IL-15, IP-10, MCP-1, VEGF, CRP) were measured in plasma from 195 PWH on ART and depressive symptoms were assessed using Beck Depression Inventory-II (BDI-II) scores. Logistic regression and mixed-effects models were used to examine the associations between inflammation biomarkers and depressive symptoms at baseline and over 18 months of follow-up. PWH had a median age of 52 years, with 95% being virally suppressed below 200 copies/mL, 33% having high depressive symptoms, and 62% having ≥1 medical comorbidity (HCV, cardiovascular disease, diabetes, chronic kidney disease, chronic lung disease). VEGF levels were increased in PWH with high vs. low depressive symptoms (p = 0.01). The association between VEGF and depressive symptoms remained significant in covariate-adjusted models (p = 0.005) and was augmented in PWH with medical comorbidities (p = 0.002). Other inflammation biomarkers were increased in PWH with medical comorbidities, but not significantly different between groups stratified by depressive symptoms. Among PWH with high depressive symptoms, biomarker clustering identified inflammatory and noninflammatory subgroups distinguished by levels of VEGF/MCP-1/IL-8 or IL-6/CRP and prevalence of HCV, cardiovascular disease, and diabetes. These findings suggest that VEGF is a biomarker associated with depressive symptoms in PWH on ART and may identify a subtype of depression for targeted interventions. Full article

Combined antiretroviral therapy (cART) has transformed HIV into a manageable chronic disease. However, people living with HIV (PLWH) experience a 16-year reduction in comorbidity-free life expectancy compared to HIV-negative individuals, driven by persistent chronic immune activation despite virological suppression. Serious non-AIDS events (SNAEs)—including cardiovascular disease, metabolic disorders, and malignancies—now represent the predominant cause of morbidity. This narrative review provides a clinician-oriented synthesis of immunopathophysiological mechanisms driving chronic inflammation in treated HIV infection, focusing on the gut–immune axis, restriction factors, trained immunity, biomarker-guided risk stratification, and therapeutic strategies. We searched PubMed/MEDLINE, Embase, and Web of Science through April 2026 using terms related to HIV chronic immune activation, gut-associated lymphoid tissue, microbial translocation, inflammaging, restriction factors, trained immunity, and biomarkers. This review followed the SANRA checklist. Irreversible destruction of gut-associated lymphoid tissue (GALT), intestinal barrier dysfunction, microbial translocation, maladaptive trained immunity, persistent myeloid activation with NLRP3 inflammasome signaling and cellular senescence, and viral reservoir persistence collectively perpetuate systemic inflammation. Biomarkers, including sCD14, IL-6, and suPAR, independently predict mortality but are not pathogen-specific. The REPRIEVE trial demonstrated a 36% reduction in cardiovascular risk with pitavastatin (HR 0.64, 95% CI 0.48–0.84), validating inflammation as a therapeutic target. Integration of early cART, statin therapy, optimal antiretroviral selection, and emerging strategies—including GLP-1 receptor agonists and gut-directed therapies—offers a practical framework for reducing inflammation-associated comorbidities in virologically suppressed PLWH. Full article

Background/Objectives: Adolescents living with HIV (ALHIV) face compounded health and psychosocial challenges while managing lifelong antiretroviral therapy (ART). Mental health difficulties among ALHIV are strongly associated with suboptimal adherence and disengagement from care. While mental illness is well documented, limited empirical evidence exists on the influence of positive mental wellness on adherence self-efficacy among ALHIV. This study assessed mental wellness among ALHIV and identified key psychosocial predictors of adherence self-efficacy in public healthcare facilities in Cape Town, South Africa. Methods: A cross-sectional survey was conducted among ALHIV (N = 251) aged 10–19 years who were receiving ART at public healthcare facilities across the Cape Town metropole. Participants completed an electronic questionnaire that assessed ten mental wellness domains and adherence self-efficacy. Descriptive statistics were calculated to summarise participant characteristics and mental wellness scores, while Pearson correlations and multiple linear regression were done to identify associations and independent predictors of adherence self-efficacy using SPSS v29. Results: Most participants were aged 15–19 years (76.9%) and diagnosed with HIV at birth (68.9%). Mental wellness scores were high across all domains (M = 3.14–3.71). Hope (M = 3.71), spirituality (M = 3.58), and purpose in life (M = 3.52) were the highest-rated domains. All mental wellness domains were positively correlated with adherence self-efficacy (p < 0.001), with the strongest associations being purpose in life (r = 0.66), self-acceptance (r = 0.66) and resilience (r = 0.66). Hope (p < 0.001), resilience (p = 0.001), purpose in life (p = 0.03) and self-acceptance (p = 0.012) emerged as significant independent predictors. Conclusions: Positive mental wellness and adolescent-centred psychosocial support in routine HIV care may strengthen adherence self-efficacy and support adolescents’ confidence in managing treatment. Full article

The human gut microbiome is essential for immune regulation and mucosal homeostasis, functions that are profoundly disrupted during HIV infection. Early viral replication in the gut-associated lymphoid tissue (GALT) triggers a self-reinforcing cycle of CD4⁺ T-cell depletion, epithelial barrier breakdown, and increased microbial translocation. This persistent immune activation continues even under effective antiretroviral therapy (ART). A growing body of evidence indicates that HIV infection is consistently associated with alterations in gut microbial communities. This dysbiosis is typically characterized by fewer beneficial butyrate-producing commensal bacteria and an enrichment of pro-inflammatory microbial taxa. It also involves disturbances in key microbial metabolites, including short-chain fatty acids (SCFAs) and tryptophan catabolites. Such changes not only exacerbate systemic inflammation but may also contribute to incomplete immune reconstitution and the persistence of latent viral reservoirs despite long-term ART. In this review, we summarize current knowledge of microbiome–HIV interactions, with particular emphasis on the mechanisms through which gut dysbiosis contributes to immune dysfunction and viral persistence. We discuss recent advances in multi-omics technologies, as well as experimental systems such as gnotobiotic and humanized mouse models and intestinal organoid platforms that are helping to elucidate these complex interactions. Furthermore, we evaluate emerging microbiome-targeted interventions—including probiotics, prebiotics, fecal microbiota transplantation, and engineered bacterial therapeutics—and consider their potential role as adjunctive strategies in HIV treatment and cure research. By integrating microbiological, immunological, and clinical perspectives, this review highlights key knowledge gaps and outlines future research directions aimed at harnessing the gut microbiome as a novel therapeutic avenue in HIV management and eradication. Full article

Background: Durable virological suppression is achieved in the majority of people living with HIV (PLWH) receiving contemporary antiretroviral therapy (ART). However, a subset of patients experience persistent low-level viremia (LLV), the clinical relevance and underlying determinants of which remain incompletely understood. Methods: Adult PLWH followed between 1 January 2005 and 31 December 2025 were retrospectively evaluated. LLV was defined as detectable HIV-1 RNA < 200 copies/mL on at least two consecutive measurements during follow-up in individuals receiving ART for at least 6 months. Patients with sustained virological suppression served as controls. Propensity score matching (1:1) was performed using variables associated with LLV in univariate analyses. Multivariable logistic regression analysis was applied to identify factors independently associated with LLV, and a p value < 0.05 was considered statistically significant. Results: Among 880 PLWH, 45 patients with LLV and 113 virologically suppressed controls were included. LLV was associated with lower baseline CD4+ T-cell counts, higher baseline HIV-1 RNA levels, delayed virological suppression at weeks 8 and 24, increased frequency of AIDS-defining illnesses and a higher prevalence of metabolic comorbidities, including hypertension, diabetes mellitus or dyslipidemia in univariate analysis. After propensity score matching, 32 patients remained in each group, with no clear association between low-level viremia and antiretroviral regimen class. Multivariable regression analysis showed baseline CD4+ T-cell count < 200 cells/µL, and the presence of ≥1 metabolic comorbidity (hypertension, diabetes mellitus or dyslipidemia) remained independently associated with LLV. Conclusions: Our findings suggest that LLV is associated with host-related factors rather than antiretroviral regimen failure. The coexistence of immunological impairment and metabolic comorbidities in patients with LLV underscores the importance of comprehensive clinical evaluation. Full article

Antiretroviral therapy (ART) effectively suppresses HIV-1 replication but does not purge the latent HIV-1 reservoir. Strategies aimed at HIV-1 latency reversal and subsequent elimination of infected cells are being explored. Targeting the inhibitor of apoptosis proteins (IAP) and DEAD-box polypeptide 3 (DDX3) RNA helicase reduces the HIV-1 reservoir ex vivo. However, the mechanisms driving apoptosis of HIV-1 infected cells remain unclear. Here, we uncovered the mechanism regarding HIV-1 transcriptional activation and induction of apoptosis specific for HIV-1 infected cells using an acute in vitro infection model. Inhibition of IAP by second mitochondrial-derived activator of caspases mimetic (SMACm; AZD5582) resulted in activation of non-canonical NF-κB pathway (RelB/p52) that induced HIV-1 transcription, confirming previous reports, whereas inhibition of DDX3 sensitized HIV-1 infected cells for apoptosis (DDX3i; FH1321). Transcriptome analysis revealed that HIV-1 actively suppressed apoptosis-related genes in HIV-1 infected cells. SMACm treatment resulted in a broad induction of these genes irrespective of infection. Notably, DDX3 inhibition specifically restored the expression of the majority of HIV-1 suppressed genes, and when combined with SMACm, restored almost all HIV-1 downregulated genes, thereby rendering HIV-1 infected cells sensitive to apoptosis. Thus, our data strongly suggest that inhibition of host factors IAP and DDX3 not only induces activation of HIV-1 transcription but also restores HIV-1 suppressed apoptotic processes in infected cells. Full article

Angola is one of the countries with the highest HIV-1 genetic diversity, yet the implications of this diversity for antiretroviral therapy remain insufficiently characterised. Following the introduction of dolutegravir (DTG) in Angola in 2021, evaluating transmitted drug resistance prior to its widespread implementation is essential to inform treatment strategies and establish a baseline for future surveillance. In this study, 243 blood samples were collected from treatment-naïve people living with HIV attending the General Hospital of Benguela, Angola. The integrase coding region of proviral DNA was amplified and sequenced using the Sanger method. Phylogenetic relationships were inferred using a maximum likelihood approach, recombinant forms were characterised by bootscanning analysis, and resistance-associated mutations to integrase strand transfer inhibitors were identified using Stanford HIVdb, ANRS-MIE, and IAS-USA algorithms. A total of 92 integrase sequences were successfully obtained, revealing 16 distinct genetic forms, with unique recombinant forms accounting for 50.0%, followed by subtype C (10.9%) and sub-subtype F1 (8.7%). Five accessory mutations (L74I, L74M, Q95K, T97A, and E157Q) and one major mutation (E92G) were detected, corresponding to an overall prevalence of 28.8% (23/80). These findings highlight the extensive HIV-1 genetic complexity in Angola and support the continued use of DTG-based regimens, while underscoring the importance of sustained surveillance of integrase inhibitor resistance. Full article

Background: People living with HIV (PLWH) are increasingly reaching older ages due to the success of antiretroviral therapy. However, aging with HIV is associated with increased risk of multimorbidity, neurocognitive impairment, frailty, psychosocial stress, and functional decline. Multidomain geriatric screening framed within an Age-Friendly 4Ms Framework (Mentation, Medication, Mobility, What Matters Most) and consideration of multi-complexity may help identify aging-related vulnerabilities and guide multidisciplinary care with greater impact on patient outcomes. However, real-world implementation of such programs within HIV clinical settings remains limited. Methods: We conducted a retrospective analysis of adults aged ≥50 years enrolled in a multidisciplinary Healthy Aging Program within a large, integrated HIV care system. Multidomain screening assessments included cognitive evaluation (Montreal Cognitive Assessment), mental health screening (PHQ-2, GAD-2), functional assessment (Katz ADL, Lawton IADL), frailty screening (Edmonton Frail Scale), and intrinsic capacity domains using the WHO Integrated Care for Older People (ICOPE) framework. Screening results, referrals, clinical interventions, and cardiometabolic risk management measures were extracted from clinical program databases and electronic medical records. Results: A total of 317 adults aged ≥50 years completed multidomain screening. Participants had well-controlled HIV infection, with viral suppression in 96.2% and a median CD4 count of 660 cells/mm³. Despite this, aging-related vulnerabilities were common. Overall, 78.4% of participants had at least one abnormal screening domain. Cognitive impairment was identified in nearly half of individuals screened, including mild impairment in 39.8% and moderate impairment in 8.7%. Functional limitations were identified in 10.1% of participants, while anxiety symptoms were present in 9.5%. Sensory impairments were common, including vision impairment in 36.5% of participants. Polypharmacy was prevalent, with 33.2% of participants prescribed five or more chronic medications. Screening frequently generated multidisciplinary referrals, including behavioral health services (42.3%), social work support (42.9%), and pharmacist-led cardiometabolic risk review (56.8%). Age-stratified analyses demonstrated similar prevalence of screening abnormalities across age groups, including individuals aged 50–59 years. Modest improvements in cardiometabolic preventive care were observed during follow-up. Statin utilization increased from 65.6% at baseline to 70.0% at 12 months, and LDL cholesterol declined modestly during the observation period. Conclusions: Multidomain screening integrated into routine HIV care identified a high prevalence of aging-related vulnerabilities among PLWH aged ≥50 years despite excellent virologic control. These findings suggest that aging-related risk in HIV is not adequately captured by chronological age alone and support early, universal implementation of multidomain screening within HIV care models. Full article

Viral infections of the central nervous system produce memory impairment through mechanisms that extend beyond acute neuronal injury. Herpes simplex virus type 1, human immunodeficiency virus, varicella zoster virus, cytomegalovirus, Epstein–Barr virus, influenza, SARS-CoV-2, West Nile virus, and Zika virus each enter or engage the brain through distinct routes, yet converge on four shared molecular pathways that selectively damage hippocampal circuits: mitochondria-associated membrane (MAM) dysfunction, chronic neuroinflammation, blood–brain barrier (BBB) disruption, and impaired CREB-BDNF signaling. These pathways specifically compromise the dentate gyrus, CA3, and CA1 subfields, producing predictable deficits in pattern separation, associative retrieval, and temporal memory binding. Antiretroviral and antiviral therapies suppress viral replication but fail to reverse organelle-level dysfunction, leaving most hippocampal injury unaddressed. Emerging plasma biomarkers, p-tau217, neurofilament light chain, and GFAP, combined with hippocampal subfield MRI, now enable mechanistic stratification before irreversible circuit loss occurs. This review proposes, as a unifying hypothesis, that virus-associated memory impairment represents a convergent hippocampal syndrome driven by shared downstream pathways, and that combination therapies targeting these pathways simultaneously offer greater therapeutic promise than pathogen-specific approaches alone. The evidentiary basis for this framework varies across pathogens and conditions; direct mechanistic evidence, mechanistic analogy, and preclinical data are distinguished throughout. Full article

HIV-associated neurocognitive disorders (HAND) arise from HIV infection of the central nervous system, resulting in chronic neuroinflammation and progressive neuronal damage that impair cognitive, motor, and behavioral functions. Clinically, HAND encompasses a spectrum of neurological impairments ranging from asymptomatic neurocognitive impairment to severe HIV-associated dementia. Despite the widespread use of combination antiretroviral therapy (cART) and significant improvements in the life expectancy of people living with HIV, HAND remains prevalent and continues to pose a major clinical challenge. One of the primary limitations of cART is the limited penetration of many antiretroviral drugs across the blood–brain barrier (BBB), thereby allowing the persistence of viral reservoirs within the CNS and contributing to sustained neuroinflammation and neuronal damage. To address these challenges, novel nanotherapeutic strategies have been developed to enhance the delivery of antiretroviral agents to the brain. These approaches include targeted delivery systems and the co-delivery of therapeutics across the BBB through mechanisms such as receptor-mediated transcytosis and other transport pathways. In this review, we discuss the pathophysiological challenges associated with HAND and recent advances in nanotherapeutic approaches designed to improve treatment efficacy. We also discuss the current state of the art in vitro and in vivo models used to test the efficacy of these advanced therapeutics. Finally, we outline the remaining challenges and future prospects for the development of nanotherapeutics to improve the treatment of HAND. Full article

Antiretroviral drugs (ARVDs) remain the cornerstone of HIV/AIDS management, but their therapeutic efficacy and safety are highly influenced by bioconversion processes such as hepatic metabolism and enzymatic transformation. Variability in metabolic pathways, mediated by cytochrome P450 enzymes and other liver-based systems, contributes to interindividual differences in drug response, toxicity, and resistance. Recent advances in artificial intelligence, particularly artificial neural networks (ANNs), offer promising tools for modeling and optimizing these complex bioconversion processes. ANNs are capable of learning nonlinear relationships from high-dimensional datasets, making them ideal for predicting the pharmacokinetic parameters, enzyme–substrate interactions, and metabolic stability of ARVDs. This review explores the emerging role of ANNs in understanding and optimizing the metabolic transformation of antiretroviral agents. Key applications are discussed, including prediction of drug–enzyme interactions, in silico modeling of hepatic clearance, and simulation of enzyme kinetics. The integration of molecular descriptors, omics data, and clinical parameters into ANN models allows for improved prediction accuracy and personalized therapy. Furthermore, ANN-based tools can aid in early-stage drug development by identifying metabolic liabilities and guiding structural modifications to enhance metabolic stability. Despite their potential, challenges such as data scarcity, model interpretability, and standardization remain. Future research should focus on hybrid models combining ANN with mechanistic pharmacokinetics, the incorporation of real-world patient data, and validation against experimental outcomes. Overall, ANNs represent a powerful approach to optimizing ARVDs bioconversion, with the potential to improve efficacy, reduce toxicity, and support the development of next-generation antiretroviral therapies Full article

A within-host HIV dynamics model incorporating latent reservoirs, distributed time delays, and a B-cell-mediated humoral immune response is developed and analyzed mathematically. The model includes five compartments: uninfected CD4⁺ T cells, latently infected cells, actively infected cells, free virions, and B cells. Four distinct distributed delays are introduced to account for the periods between viral entry and the emergence of latently or actively infected cells, reactivation of latently infected cells, and intracellular virion production. For the non-delayed system, the basic reproduction number ${\mathcal{R}}_0$ is derived using the next-generation matrix method. Using Lyapunov functions and LaSalle’s Invariance Principle, a sharp threshold dynamic is proven: the infection-free equilibrium is globally asymptotically stable (GAS) when ${\mathcal{R}}_0\le 1$, whereas a unique endemic equilibrium is GAS when ${\mathcal{R}}_0>1$. For the full distributed-delay system, a delay-dependent reproduction number ${\mathcal{R}}_0^d$ is defined. The global asymptotic stability of the infection-free equilibrium is established for ${\mathcal{R}}_0^d\le 1$, and the global asymptotic stability of the endemic equilibrium is established for ${\mathcal{R}}_0^d>1$, using suitably constructed Lyapunov functionals that account for the delay history. Numerical simulations validate the analytical threshold behavior. A sensitivity analysis of ${\mathcal{R}}_0^d$ identifies the most influential parameters for potential intervention. A treatment-dependent reproduction number is derived, and the critical drug efficacy required for viral eradication is determined. The intracellular production delay is shown to act as a critical threshold for infection clearance. Full article

Advances in antiretroviral therapy have transformed infection with HIV into a manageable chronic disease, increasing the survival of people living with HIV, who are also undergoing a demographic aging process marked by the emergence of non-communicable chronic diseases. This study aims to map and analyze how the scientific literature addresses the organization and integration of care in the HIV-NCD syndemic, identifying implications for nursing and for health systems. This is a Rapid Scoping Review, using the databases PubMed, Scopus, CINAHL, and LILACS. Data synthesis was conducted using Microsoft Excel. The research was structured using the PCC framework: Population—people living with HIV (≥18 years); Concept—organization and integration of care in the HIV-NCD syndemic, including care models, care coordination, service integration, and the role of nursing; and Context—health services and systems. Twenty-three studies were included, most of which used qualitative methodology, were conducted in sub-Saharan Africa, and had predominantly female samples. This study demonstrated that the organization of care in the HIV-NCD syndemic remains predominantly characterized by fragmented models, which are insufficient to address the complexity of multimorbidity. Integrated care models emerge as a promising strategy; however, their effects remain limited in settings marked by health inequalities. Full article

To this day, the etiology of multiple sclerosis has yet to be fully comprehended by the scientific community. However, the knowledge on mechanisms leading to the development of this neurodegenerative autoimmune disorder increases daily, along with the development of new disease-modifying treatments. A correlation between Epstein–Barr Virus infection and the disease incidence has recently shed light on possible innovative antiviral therapies. Here, we review the literature on Human Endogenous Retroviral sequences as emerging actors for the impairment of remyelination as a major challenge in disease progression. Our primary focus is the HERV-W envelope protein, which has been found at elevated levels in individuals affected by this condition and is suggested here as a potential therapeutic target. We then continue analyzing the clinical cases where antiretroviral drugs have been tested to treat multiple sclerosis patients and, from successes and failures, we finally narrow down our therapeutic hypothesis to the administration of Nucleoside-analog Reverse Transcriptase Inhibitors to target the HERV-W envelope protein, possibly leading to remyelination and significantly improving the condition of those affected by the disease. The main purpose of this review is to present a rationale for the therapeutic potential of this drug class and offer a new perspective for therapeutic options against multiple sclerosis. Full article

This study aimed to explore and describe the barriers to Antiretroviral Therapy (ART) adherence among children in Ekurhuleni, Gauteng. A quantitative, cross-sectional design using a survey method was employed. Convenience sampling was used to recruit 157 parents, guardians, and caregivers (PGCs) who consented to participate in the study. Data was collected using self-report questionnaires and analysed using descriptive statistics and frequency distributions. The study was not designed or statistically powered to formally test associations between variables; therefore, only descriptive statistical analyses were conducted. The reliability and validity of the instrument were ensured, and ethical clearance was obtained from the relevant authorities prior to data collection. The study was conducted in accordance with established ethical principles and in compliance with the Declaration of Helsinki. The findings revealed that there were multiple barriers to children’s adherence to ART. Approximately one-third of PGCs reported being fully informed about the importance of ART adherence, while the majority indicated being only partially informed. Missed doses emerged as a significant challenge, with a substantial proportion reporting missed medication on one or more days, and only 31.2% administering ART consistently on time. Difficulties in understanding blood test results were also reported. In addition, a notable proportion of PGCs admitted to missing clinic appointments. These findings emphasize the need for strengthened caregiver education, ongoing support, and tailored interventions directed at primary health care nurses to promote consistent ART adherence among children. Full article