Search Results (352)

Cardiovascular disease (CVD) is increasingly recognized as a significant comorbidity in people living with HIV (PWH), contributing to increased morbidity and mortality. Epidemiological studies indicate that PWH have a 1.2–2-fold higher risk of myocardial infarction (MI) and other CVD events compared to HIV-negative individuals. While the mechanisms underlying HIV-associated CVD are not fully understood, they are likely to include a combination of cardiovascular-related adverse effects of HIV medications, vascular dysfunction caused by HIV-induced monocyte activation, and cytokine secretion, in addition to existing comorbidities and lifestyle choices. This comprehensive review examines the complex relationship between HIV infection and CVD, highlighting key pathophysiological mechanisms such as chronic immune activation, inflammation, endothelial dysfunction, and the role of antiretroviral therapy (ART) in promoting cardiovascular risk. Alongside conventional risk factors such as smoking, hypertension, and dyslipidemia, HIV-specific elements, especially metabolic abnormalities associated with ART, significantly contribute to the development of CVD. Prevention strategies are crucial, focusing on the early identification and management of cardiovascular risk factors as well as optimizing ART regimens to minimize adverse metabolic effects. Clinical guidelines now recommend routine cardiovascular risk assessment in PWH, emphasizing aggressive management tailored to their unique health profiles. However, challenges exist in fully understanding the cardiovascular outcomes in this population. Future research directions include exploring the role of inflammation-modulating therapies and refining sustainable prevention strategies to mitigate the growing burden of CVD in PWH. Full article

Defective HIV-1 proviruses harboring mutations and/or large internal deletions represent the majority of HIV-1 sequences found in circulating peripheral blood mononuclear cells of people living with HIV with viremia suppressed by combination antiretroviral therapy; indirect evidence suggests that such sequences are transcriptionally active and may contribute to immune activation. In this study, we present a new approach allowing for high-efficiency screening, immortalization, and targeted enrichment of HIV-positive CD4⁺ T-cells isolated from people living with HIV. Using this method, we were able to isolate and expand patient-derived cells, identify mutations and deletions via sequencing, and confirm that those proviruses were transcriptionally and translationally active in vitro. Moreover, our findings indicate that the majority of proviral sequences circulating in suppressed HIV-infected patients may undergo 3′-LTR deletions, suggesting that sequence diversity reported using LTR-to-LTR amplification and sequencing approaches may indeed be underscored. Full article

Prior to the introduction of antiretroviral therapy (ART), people with HIV (PWH) had high risk of fungemia. No systematic review has assessed the prevalence of fungemia in PWH after the introduction of combination ART in 1996. The primary objective of this systematic review was to determine the prevalence of fungemia in adult PWH after 1996. Furthermore, we aimed to compare the prevalence of fungemia in different ART time periods to determine geographic differences and fungal pathogen distribution. A systematic literature search was performed on 7 March 2025 across six databases and the study quality was assessed using the Newcastle–Ottawa scale. Prevalence estimates were extracted, and a meta-analysis was performed using a random effects model. Twelve studies comprising 27,729 PWH were included. The overall pooled prevalence in PWH was 3.3% (95% CI: 1.53; 4.96%, I² = 98.9%). The most common pathogen to cause fungemia was Talaromyces marneffei with a prevalence of 4.8%, although this pathogen was limited to studies from Asia. The highest prevalence of fungemia in PWH was 6.8% in Asia. The prevalence of fungemia was 5.8% between July 1996–September 2015 and 1.0% between September 2015–January 2025, but the difference was not statistically significant (p = 0.273). However, all findings were limited by very low certainty of evidence and should be interpreted with caution. In conclusion, our findings suggest that fungemia persists among PWH despite ART, especially in Asia. Given the limited available evidence, it was not possible to determine whether the prevalence of fungemia changed following the change in ART treatment guidelines in September 2015. The protocol is registered in PROSPERO (CRD420251005081). Full article

Human immunodeficiency virus type 1 (HIV-1) continues to be a major global health burden. Combination antiretroviral therapy (cART) effectively abrogates HIV-1 replication and has transformed HIV-1 infection from a fatal to chronic disease. While ART can suppress viremia to undetectable levels in people living with HIV-1 (PWH), a small reservoir of cells infected with replication-competent HIV-1 persists and can lead to viral rebound upon ART interruption. This persistent HIV-1 reservoir can be quantified and characterized by measuring replication of infectious HIV-1 using a quantitative viral outgrowth assay (qVOA), or by measuring HIV-1 DNA, RNA, or protein levels as a proxy for the reservoir. Tools to quantify the reservoir in these distinct molecular compartments have been developed for HIV-1 subtype B, which is predominant in the Global North. However, non-B subtypes constitute the majority of HIV-1 infections worldwide. Here, we discuss the wide range of reservoir quantitation and characterization tools, explore their limitations, and, where applicable, their adaptations to non-B subtypes. We conclude that standardized tools should be used to characterize reservoir dynamics of HIV-1 B and non-B subtypes. These tests should be well-validated and accessible to all laboratories world-wide to be able to draw conclusions about subtype-specific reservoir dynamics. Full article

HIV-1 integrase strand transfer inhibitors (INSTIs) are pivotal to antiretroviral therapy. However, the emergence of drug-resistant mutations necessitates the development of new agents. Here, we present ACC017 as a novel INSTI candidate. ACC017 demonstrated potent activity against the laboratory-adapted HIV-1_IIIB strain (EC₅₀ = 0.59 nM; SI > 34,525) and maintained efficacy against a panel of drug-resistant strains (EC₅₀ range from 0.34 to 9.12 nM) and clinical isolated strains (EC₅₀ range from 0.11 to 1.78 nM). Mechanism of action studies confirmed its ability to inhibit the integrase enzyme (IC₅₀ = 9.19 nM) and effectively block viral genome integration. Notably, in vitro resistance selection primarily yielded D232N and R263K mutations, without the emergence of G140S/A/C/R or Q148H/R/K. This promising profile, combined with synergistic interactions with other antiretroviral drugs, positions ACC017 as a potential therapeutic option. Full article

Background/Objectives: Both HIV infection and antiretroviral therapy contribute to dyslipidemia and abnormal body fat distribution in people living with HIV (PLWH). Exercise training is an effective intervention to protect against these metabolic changes. However, little is known about the mechanisms underlying the impact of exercise training on lipid metabolism in PLWH. This study aimed to comparatively evaluate the effect of high-intensity functional circuit training on the plasma lipidome of PLWH and HIV-negative subjects (control). Methods: PLWH (n = 13) and control (n = 14) were submitted to 8 weeks of exercise training. Body composition, anthropometric, and biochemical parameters were measured. Plasma was obtained in a fasting state for lipidomic analysis. Results: Anthropometric and biochemical parameters revealed lower levels of leptin, HDL-C, body fat %, and BMI combined with elevated aspartate transaminase (AST) and Homeostasis Model Assessment of β-cell function (HOMA_beta) in PLWH when compared to control subjects that persisted from baseline to post-exercise training. Nonetheless, contrasting levels of adiponectin, fasting insulin, and phosphatidylcholine-containing lipids observed at baseline were equalized after training in PLWH. In control subjects, significant reductions in concentrations of triglycerides alongside phosphatidylinositol and glycosylated ceramides were observed post-exercise training. By contrast, PWLH displayed an increase in diglycerides, acylcarnitines, and free cholesterol levels after exercise training, together with decreased concentrations of free fatty acids, cholesteryl esters, and glycosylated ceramides. Conclusions: In addition to specific lipidome alterations in each group, particularly driven by improved insulin resistance in PLWH, this study showed concomitant modulation of several glycerophospholipids and sphingolipids, suggesting health-promoting effects of short-term exercise training. Collectively, these modulated lipid species represent interesting targets for future lipidomic-based studies evaluating not only the effects of exercise training but also the molecular mechanisms resulting in a healthier plasma lipidome profile. Full article

Background: Cancer epidemiology data for people living with human immunodeficiency virus (PLWH) in Thailand, particularly in the era of combination antiretroviral therapy (ART), remain limited. In this study, we describe the prevalence, temporal trends, clinical characteristics, and survival outcomes of patients with AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs). Methods: We retrospectively reviewed adult PLWH diagnosed with malignancy at Songklanagarind Hospital in Thailand during 2003–2023. Demographic, human immunodeficiency virus (HIV)-related, and clinical data were analyzed using chi-square and Wilcoxon rank-sum tests and the Kaplan–Meier method. Results: Among 444 patients, 231 had NADCs and 213 had ADCs. The NADC proportion increased markedly over time. Common ADCs included non-Hodgkin lymphoma and cervical cancer; common NADCs included lung cancer, non-nasopharyngeal head and neck cancer, and hepatocellular carcinoma. Compared with patients with ADCs, those with NADCs were older, more often male, and had higher proportions of undetectable HIV viral load, CD4 counts ≥200 cells/µL, and ART use. Approximately one-third of patients presented with advanced-stage disease, and the median overall survival was 15.9 months. Conclusions: Over two decades, NADCs have become the predominant malignancy in Thai PLWH, associated with older age, male sex, and improved immune function. This reflects the evolving cancer risk in the era of combination ART. We suggest employing multidisciplinary approaches involving HIV and cancer care to improve survival outcomes and integrating age-appropriate screening for common NADCs into HIV care. Full article

Antiretroviral therapy (ART) effectively suppresses HIV replication but fails to eradicate latent reservoirs, leading to viral rebound after interruption. Chimeric antigen receptor (CAR) T-cell therapy offers a potential strategy to achieve durable remission. A systematic PubMed search (July 2020–June 2025) identified 253 studies on CAR-T therapy in HIV; 74 met inclusion criteria and were qualitatively analyzed. Preclinical data showed that CAR-T cells can recognize and eliminate infected cells, reach viral reservoirs, and persist long term, particularly when derived from hematopoietic stem cells. Dual-target and combination approaches with checkpoint inhibitors or latency-reversing agents enhanced antiviral efficacy. Early clinical studies confirmed safety and modest reservoir reduction. CAR-T cell therapy represents a promising step toward a functional HIV cure. Further optimization of design, integration with gene-editing technologies, and standardized clinical evaluation are required to confirm durable efficacy and safety. Full article

Background/Objectives: The emergence of drug-resistant HIV-1 strains challenges the long-term efficacy of current antiretroviral therapies. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are critical in HIV-1 treatment; however, the need for new candidates with improved resistance profiles and pharmacokinetics remains. This study aims to design and evaluate novel NNRTIs targeting both wild-type (WT) and mutant-type (MT) HIV-1 reverse transcriptase (RT) using integrated computational strategies. Methods: We conducted a 3D-QSAR study on 33 naphthyl-diarylpyrimidine derivatives using CoMFA and CoMSIA models. We designed thirty-five novel molecules based on contour map insights. We applied ADMET and drug-likeness filters to prioritize ten candidates. Molecular docking was performed on WT (PDB: 3HVT) and MT (PDB: 4PUO) RT structures. The top candidates underwent 100 ns molecular dynamics (MD) simulations. We analyzed structural stability via RMSD, RMSF, and Rg, while we used SASA and MolSA to assess solvent exposure and surface compactness. Results: The CoMFA and CoMSIA models demonstrated robust predictivity (R² = 0.979/0.920, Q² = 0.643/0.546, R²_test = 0.747/0.603). P14 and P43 showed higher binding affinities than nevirapine and favorable ADMET profiles. MD simulations confirmed stable binding in WT-RT and adaptive flexibility in MT-RT. SASA and MolSA analysis revealed favorable conformational compaction. Drug-likeness profiles indicated optimal log P, strong hydrogen bonding, and acceptable bioavailability. Conclusions: P14 and P43 demonstrate strong potential as NNRTI leads, combining binding affinity, structural stability, and favorable pharmacokinetics, supporting further experimental development. Full article

Human Immunodeficiency Virus (HIV) infection is associated with a wide spectrum of urological manifestations, reflecting both the direct effects of viral infection and the indirect consequences of immunosuppression, opportunistic infections, malignancies and long-term combined antiretroviral therapy (cART). This narrative review provides a contemporary, multifaceted overview of the clinical and pathological presentations of urological conditions in people living with HIV (PLWHIV), based on articles published between 1989 and 2025. Conditions discussed include HIV-associated nephropathy (HIVAN), opportunistic genitourinary infections, malignancies such as Kaposi sarcoma and lymphoma, as well as non-infectious complications such as HIV-associated nephropathy and erectile dysfunction (ED). The review highlights the evolving epidemiology of these conditions in the cART era, with a noted decline in opportunistic infections but a rising burden of chronic kidney disease and malignancies, largely due to improved survival and ageing of the HIV-positive population. Pathological insights are explored and discussed, including mechanisms of HIV-associated renal injury, such as direct viral infection of renal epithelial cells and genetic predispositions linked to Apolipoprotein L1 (APOL1) variants. In addition, psychosocial factors, including anxiety, stress, stigma, and alcohol use, are discussed, as they may contribute to late presentation to clinical urology services. The review also considers the challenges faced in low and middle-income countries, the impact of HIV on urological services, and the important role of palliative care in advanced disease. Ultimately, this review underscores the need for early recognition, comprehensive diagnostic and surgical evaluation, and integrated social, psychological, and palliative management strategies tailored to the unique needs of PLWHIV. A deeper understanding of the interplay between HIV, cART, psychosocial determinants, and urological health is essential for improving patient outcomes and guiding future research in this evolving field. Full article

Human immunodeficiency virus (HIV) remains a global public health challenge. Antiretroviral therapy (ART) improves outcomes by suppressing viral replication and enabling immune recovery, yet the early molecular mechanisms of immune-related transcriptional change after ART remain insufficiently characterized. We enrolled eight ART-naïve male patients with HIV aged 18–35. Peripheral blood mononuclear cells (PBMCs) were collected before and after 24 weeks of combination ART (TDF, 3TC, DTG) and underwent bulk RNA-seq (Illumina HiSeq 1500, Illumina, Inc., San Diego, CA, USA). Differential expression was assessed with DESeq2 (paired design); gene set enrichment analysis (GSEA), principal component analysis (PCA), hierarchical clustering, and protein–protein interaction (PPI) networks (STRING/NetworkX) explored functional patterns and transcriptomic shifts. We identified 87 differentially expressed genes, including 67 downregulated interferon-stimulated genes (e.g., IFI44L, ISG15, STAT1) and 20 upregulated transcripts, mostly pseudogenes related to ribosomal proteins. Functional enrichment revealed suppression of type I interferon and other antiviral signaling pathways. PCA and hierarchical clustering indicated a post-ART transcriptional shift. These findings suggest that early immune recovery following ART involves downregulation of chronic interferon-driven activation. This observation may correspond to partial restoration of T-cell functional capacity, reduced immune exhaustion, and a rebalanced antiviral immune environment. Full article

Parathyroid gland disorders, including secondary hyperparathyroidism, have emerged as significant endocrine complications in people living with HIV (PLWHIV). This narrative review synthesises recent evidence on the prevalence, mechanisms, and clinical implications of parathyroid dysfunction in PLWHIV. HIV infection, combined antiretroviral therapy (cART), and immune activation contribute to parathyroid dysfunction, with cART regimens, particularly Tenofovir Disoproxil Fumarate (TDF), exacerbating these disturbances by altering the calcium and parathyroid hormone (PTH) dynamics. Studies show that PTH levels in PLWHIV on TDF were significantly elevated compared to those on non-TDF-based cART regimens. Histopathological studies highlight a higher prevalence of parathyroid hyperplasia in PLWHIV, often linked to chronic deficiencies in calcium, magnesium, and vitamin D, as well as immune dysregulation. The dysfunction observed ranges from inappropriate elevation of PTH levels to hypoparathyroidism, leading to rapid bone density loss and an increased fracture risk. Despite the fact that HIV is a condition associated with high malignancy, parathyroid malignancy is a very rare issue. Despite the growing recognition of these complications, routine screening for PTH and bone health remains inadequate in standard clinical HIV care. This review advocates for incorporating routine monitoring of serum PTH, calcium, phosphate, and vitamin D levels, especially in those on TDF-based cART. Early detection of subclinical parathyroid dysfunction can prevent complications such as secondary hyperparathyroidism and neuromuscular symptoms. Clinicians should be aware of atypical biochemical presentations, such as elevated PTH with normal calcium, which may indicate cART-induced dysregulation, improving patient management and outcomes. Full article

Background: Major advances in antiretroviral therapy (ART) have transformed HIV into a chronic condition, yet drug resistance, long-term toxicities, adherence challenges, and persistent viral reservoirs continue to drive innovation. Objectives: To map and synthesize recent developments in anti-HIV drugs and delivery platforms with a focus on (i) new molecules in clinical development and (ii) novel mechanisms of action, following a scoping review framework aligned with PRISMA-ScR. Sources: We interrogated PubMed, Embase.com, Web of Science, and Scopus (January 2020–September 2025) and screened abstracts from CROI, IAS/AIDS, IDWeek, and HIV Glasgow (2023–2025). Content: The evidence base underscores capsid inhibition (lenacapavir) for multidrug-resistant HIV and its expansion into prevention, long-acting intramuscular maintenance with cabotegravir/rilpivirine, maturation inhibitors (zabofiravir), and attachment inhibition with fostemsavir. Broadly neutralizing antibodies (bNAbs) can sustain ART-free suppression in selected individuals. Ultra-long-acting delivery systems are advancing toward translational evaluation. Summary: The pipeline is diversifying toward less frequent dosing, new targets, and combination strategies. Successful and ethical implementation will require resistance-informed selection, equitable access, and reimagined healthcare delivery models that accommodate long-acting technologies. Full article

The use of highly active combined antiretroviral therapy (cART) has increased life expectancy in people living with HIV (PLWH). As a result of ongoing monitoring and surveillance in established HIV out-patient clinics, thyroid dysfunction amongst this population has become increasingly reported. In this narrative review, primary studies, case reports, and meta-analyses published on PubMed, Embase, and Cochrane were analysed. The most reported thyroid dysfunction is subclinical hypothyroidism (SCH). The prevalence of subclinical hypothyroidism was as high as 40% in PLWH with CD4 T-cell count < 350 cells/mm³, which is a level indicating a state of immunosuppression. Some less commonly reported thyroid dysfunctional conditions include overt hyperthyroidism and thyroid malignancy. Reports have linked the development of thyroid dysfunction to the use of cART, leading to immune reconstitution inflammatory syndrome (IRIS), which has also been linked to the development of Grave’s disease (GD). It is also important to check for thyroid malignancy, as PLWH are prone to having a high risk of developing non-AIDS-related or -defining cancer (NADC). Most research suggests symptom-driven monitoring. However, evidence also suggests that monitoring with cART status change, monitoring for patients with significant comorbidities, or with immune reconstitution may be useful. The screening should include Free Thyroxine (FT4), triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) testing. Furthermore, vigilance for Grave’s disease and performing thyroid antibody checks are advised, especially once the reconstitution of T-cells is achieved. Full article

Background/Objectives: Individual plasma protein biomarkers have been shown to correlate with cognitive performance in people with HIV (PWH). This study aimed to investigate the association between plasma proteomic signatures and attention/working memory in virologically well-controlled women with HIV (WWH). Methods: Seventy-seven WWH from three Women’s Interagency HIV Study (WIHS) sites completed neuropsychological (NP) testing and a blood draw. Selected protein biomarkers (200 total) were analyzed using a multiplexing method. Results: Random forest analysis was used to identify the top 10 biomarkers that were each positively or negatively associated with attention/working memory. Ingenuity pathway analysis (IPA) was used to facilitate data interpretation. Tumor necrosis factor receptor 1 (TNF RI), TNF RII, interleukin 1 receptor 1 (IL-1RI), and IL-6R were negatively associated with attention/working memory. Conclusions: Based on the IPA, two gene signaling networks were proposed for associating these plasma protein biomarkers with attention/working memory function. This novel methodology demonstrates how gene networks can be identified using blood draws in conjunction with cognitive assessment, and then used in random forest analysis, to derive value that can be put in IPA. Full article