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Search Results (232)

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21 pages, 850 KB  
Review
Tuberculosis Control Protocols in the European Region: A Brief Overview
by Aimilios Pliatsikas, Costas Tsiamis, Joseph Papaparaskevas, Georgia Vrioni and Athanasios Tsakris
Acta Microbiol. Hell. 2026, 71(3), 26; https://doi.org/10.3390/amh71030026 - 25 Jul 2026
Viewed by 128
Abstract
Tuberculosis (TB) continues to be a significant public health challenge in Europe, despite a sustained decline in disease incidence over recent decades. This narrative review briefly traces the historical development of TB diagnosis and focuses on the evolution of TB control protocols from [...] Read more.
Tuberculosis (TB) continues to be a significant public health challenge in Europe, despite a sustained decline in disease incidence over recent decades. This narrative review briefly traces the historical development of TB diagnosis and focuses on the evolution of TB control protocols from the early twentieth century to the present across Europe, through a longitudinal comparative analysis of its geographical regions. A literature search was conducted using publications, guidelines, and surveillance reports from the World Health Organization (WHO), the European Centre for Disease Prevention and Control (ECDC), and national public health authorities. The analysis follows a geographical framework encompassing Eastern, Western, Northern, and Southern Europe, reflecting historical, socioeconomic, and healthcare system differences. This study presents the transition from traditional diagnostic approaches based on clinical assessment, chest radiography, and smear microscopy to modern molecular and immunological techniques, including Xpert MTB/RIF assays and interferon-gamma release assays (IGRAs). Similarly, treatment strategies have evolved from sanatorium-based supportive care to standardized, evidence-based short-course regimens employing first- and second-line anti-TB drugs. However, marked regional differences remain in the implementation of contemporary protocols. Western and Northern European countries have largely adopted advanced diagnostic technologies and comprehensive surveillance systems and are approaching TB elimination targets. In contrast, Eastern Europe continues to bear a disproportionate disease burden, driven by multidrug-resistant TB, HIV co-infection, and socioeconomic disparities. TB control protocols in Southern Europe are progressively converging with those of Western Europe through the adoption of modern diagnostic approaches, standardized treatment regimens, and WHO-endorsed guidelines. The findings of this study underscore the need for greater harmonization of TB control protocols across Europe through an initiative coordinated by the ECDC/WHO. Accelerating progress toward TB elimination in the European Region will depend on expanding access to modern diagnostic technologies, implementing targeted interventions in high-burden settings, and strengthening cross-border collaboration through coordinated public health policies. Full article
16 pages, 561 KB  
Article
Clinical Characteristics and Predictors of One-Year Mortality in HIV and Non-HIV Patients with Cryptococcal Infections in a Middle-Income Setting: A Multicenter Cohort Study
by Aysun Benli, Atahan Çağatay, Berivan Şahin, Tuğba Arslan Gülen, Tuba Turunç, Emine Günal, Özlem Güler, Esra Kazak, Ferit Kuşcu, Ayça Aydın, Zeynep Karakaşoğlu, Neşe Saltoğlu, Süheyla Serin Senger, Hale Turan Özden, Buket Erturk Sengel, Recep Tekin, Oğuz Usta, Esra Gürbüz, Zehra Çağla Karakoç, Didem Akal Taşcıoğlu, İlkay Karaoğlan and Yasemin Tezeradd Show full author list remove Hide full author list
J. Fungi 2026, 12(8), 545; https://doi.org/10.3390/jof12080545 - 23 Jul 2026
Viewed by 252
Abstract
Background: Cryptococcal infections remain life-threatening fungal infections affecting both people living with HIV (PLWH) and non-HIV populations. Data from real-world cohorts in middle-income settings, particularly those including both groups, remain limited. This study aimed to evaluate the clinical characteristics and identify predictors of [...] Read more.
Background: Cryptococcal infections remain life-threatening fungal infections affecting both people living with HIV (PLWH) and non-HIV populations. Data from real-world cohorts in middle-income settings, particularly those including both groups, remain limited. This study aimed to evaluate the clinical characteristics and identify predictors of one-year mortality in patients with cryptococcal infections. Methods: In this retrospective multicenter cohort study, adult patients diagnosed with cryptococcal infection between 2013 and 2025 were included and followed for one year after diagnosis or until death. Demographic, clinical, laboratory, and treatment data were collected. Survival was analyzed using Kaplan–Meier methods and compared with the log-rank test. Cox proportional hazards regression was used to identify factors independently associated with mortality. Subgroup analyses were performed according to HIV status. Results: A total of 92 patients with an average age of 46 ± 16 years were included; 56.5% were PLWH, and 87% were immunocompromised. Central nervous system involvement was the most common presentation (64.1%). Overall one-year mortality was 46.7%. In the multivariable Cox regression analysis, altered consciousness (HR 3.110, 95% CI 1.624–5.956, p < 0.001) and disseminated infection (HR 2.155, 95% CI 1.156–4.016, p = 0.016) were independently associated with increased mortality, whereas higher serum albumin levels were independently associated with improved survival (HR 0.532, 95% CI 0.328–0.861, p = 0.010). Age remained independently associated with mortality (HR 1.025 per year, 95% CI 1.006–1.045, p = 0.010). Kaplan–Meier analysis showed significantly lower one-year survival among patients with altered consciousness and disseminated infection. Although CNS involvement was more frequent among PLWH (78.8% vs. 45%, p < 0.001), mortality rates were comparable between PLWH and non-HIV patients. Conclusions: Cryptococcal infections are associated with high mortality regardless of HIV status. Altered consciousness and disseminated infection were independently associated with one-year mortality, whereas higher albumin levels were associated with improved survival. Simple clinical parameters may contribute to early clinical risk assessment, particularly in resource-limited settings. Full article
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16 pages, 253 KB  
Article
Prevalence and Factors Associated with Lifetime HIV Testing Among Thai General Population Adults: Finding from the 6th Thai National Health Examination Survey
by Sirinan Prakot, Wichai Aekplakorn, Roengrudee Patanavanich, Masatha Thongpan, Suchanart Inwanna, Donruedee Kamkhoad, Ratchanok Phonyiam, Sukanya Kankaew, Siriphorn Na nakorn, Arissara Sawatpanich and Jittrarath Phothikul
Healthcare 2026, 14(14), 2230; https://doi.org/10.3390/healthcare14142230 - 22 Jul 2026
Viewed by 253
Abstract
Background/Objectives: HIV testing is essential for early HIV diagnosis, timely treatment initiation, and HIV prevention. Despite Thailand’s long-standing HIV prevention programs and universal access to HIV testing services, nationally representative evidence on lifetime HIV testing among Thai adults remains limited. This study [...] Read more.
Background/Objectives: HIV testing is essential for early HIV diagnosis, timely treatment initiation, and HIV prevention. Despite Thailand’s long-standing HIV prevention programs and universal access to HIV testing services, nationally representative evidence on lifetime HIV testing among Thai adults remains limited. This study aimed to estimate the prevalence of lifetime HIV testing and identify factors associated with lifetime HIV testing among Thai adults. Methods: This study was a secondary analysis of data from the 6th Thai National Health Examination Survey. A total of 11,843 Thai adults aged 20–59 years were included. Descriptive statistics were used to estimate the prevalence of lifetime HIV testing. Survey-weighted logistic regression analyses were performed to examine factors associated with lifetime HIV testing. Results: The overall prevalence of lifetime HIV testing was 41.9%, with a prevalence of 42.4% among males, and 41.4% among females. Individuals aged 30–39 years (AOR = 1.64, 95% CI: 1.43–1.87) and 40–49 years (AOR = 1.67, 95% CI: 1.41–1.99), those with secondary education (AOR = 1.64, 95% CI: 1.43–1.87) or certificate/higher education (AOR = 1.74, 95% CI: 1.48–2.05), those currently living with a partner (AOR = 1.60, 95% CI: 1.43–1.79), participants with higher monthly income (10,000–24,999 THB: AOR = 1.13, 95% CI: 1.01–1.27; ≥25,000 THB: AOR = 1.39, 95% CI: 1.13–1.70), residents in the Northern region (AOR = 1.74, 95% CI: 1.45–2.09), and those who had a relative or acquaintance living with HIV/AIDS (AOR = 1.46, 95% CI: 1.34–1.59) were more likely to have lifetime HIV testing. In contrast, Muslim participants (AOR = 0.72, 95% CI: 0.57–0.90), residents of rural areas (AOR = 0.88, 95% CI: 0.79–0.97), residents in the Central (AOR = 0.82, 95% CI: 0.69–0.98) and Southern regions (AOR = 0.83, 95% CI: 0.72–0.94), and those with higher HIV-related stigma (AOR = 0.91, 95% CI: 0.84–0.99) were less likely to have lifetime HIV testing. Conclusions: Lifetime HIV testing among Thai adults remained suboptimal, with geographic and sociodemographic disparities. Full article
(This article belongs to the Section Public Health and Preventive Medicine)
16 pages, 3631 KB  
Review
Efficacy and Safety of a Single Dose Versus Three Weekly Doses of Benzathine Penicillin G for Early Syphilis: A Systematic Review and Meta-Analysis
by Thanyarat Phumthian, Sudapree Sorasuchart and Samadhi Patamatamkul
Int. J. Transl. Med. 2026, 6(3), 26; https://doi.org/10.3390/ijtm6030026 - 26 Jun 2026
Viewed by 517
Abstract
Background/Objectives: To compare the efficacy and safety of a single dose versus three weekly doses of benzathine penicillin G (BPG) for the treatment of early syphilis. Methods: We searched Embase, PubMed, and Scopus for randomized controlled trials (RCTs) and prospective comparative [...] Read more.
Background/Objectives: To compare the efficacy and safety of a single dose versus three weekly doses of benzathine penicillin G (BPG) for the treatment of early syphilis. Methods: We searched Embase, PubMed, and Scopus for randomized controlled trials (RCTs) and prospective comparative studies published in English up to September 2025. The primary outcome was serological cure (≥4-fold decline in non-treponemal titers) at 6–12 months, analyzed on an intention-to-treat (ITT) basis. Risk of bias was assessed using RoB 2 for RCTs and ROBINS-I for non-randomized studies; certainty of evidence was rated with GRADE. Data were synthesized using random-effects meta-analysis and trial sequential analysis (TSA). Results: Three studies (n = 886) met the inclusion criteria. The primary ITT meta-analysis showed no significant difference in serological cure between the three-dose and single-dose regimens (risk ratio [RR] 1.06; 95% CI 0.92–1.21; p = 0.42), with substantial heterogeneity. In an exploratory pre-specified subgroup of patients with high baseline RPR (≥1:32), the three-dose regimen was associated with higher cure rates (RR 1.12; 95% CI 1.02–1.23; p = 0.02; I2 = 0%), but no significant benefit was seen for people with HIV (PWH) (RR 1.08; p = 0.13) or for those with CD4 counts <350 cells/mm3. Risk of bias was serious across all studies, and GRADE certainty was very low for efficacy and low for safety. In a post hoc per-protocol analysis restricted to early latent syphilis, the three-dose regimen yielded higher serological cure (pooled risk difference 12%, 95% CI 1–23; p = 0.03). TSA indicated that the evidence is inconclusive and underpowered. Conclusions: On the basis of the ITT analysis, a single dose of BPG appears to remain effective and safe for most cases of early syphilis, including in PWH, supporting current CDC and WHO recommendations. The apparent advantages of three doses in high-titer and early latent subgroups derive from exploratory and post hoc analyses of studies at high risk of bias with very low certainty of evidence and should be regarded as hypothesis-generating rather than practice-changing. Adequately powered, well-designed trials are needed before any dose stratification can be recommended. Full article
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20 pages, 3471 KB  
Article
Distinct Innate and Adaptive Immune Modules Differentially Associate with HIV Reservoir Size and Decay During Early Antiretroviral Therapy
by Wei-Zhe Li, Hui-Huang Huang, Hui-Fang Wang, Xia Li, Ming-Ju Zhou, Yu-Xuan Yang, You-Yuan Wang, Meng-Meng Zhu, Ying Sun, Si-Yuan Chen, Xing Fan, Yan-Mei Jiao, Jin-Wen Song, Ruo-Nan Xu, Cheng Zhen, Ming Shi, Chao Zhang and Fu-Sheng Wang
Cells 2026, 15(13), 1161; https://doi.org/10.3390/cells15131161 - 25 Jun 2026
Viewed by 365
Abstract
HIV reservoir size and decay represent distinct dimensions of viral persistence, yet whether they are governed by shared or separable immunological mechanisms during early antiretroviral therapy (ART) remains unclear. In this study, we employed multiparameter flow cytometry and bulk RNA sequencing to analyze [...] Read more.
HIV reservoir size and decay represent distinct dimensions of viral persistence, yet whether they are governed by shared or separable immunological mechanisms during early antiretroviral therapy (ART) remains unclear. In this study, we employed multiparameter flow cytometry and bulk RNA sequencing to analyze longitudinal immune profiles across 21 treatment-naïve people living with HIV before ART initiation and at 1 and 5 months thereafter. Our findings revealed an apparent dissociation between HIV-1 DNA levels and decay rates in peripheral blood, and the two indicators appear to be relatively independent dimensions of viral persistence. Specifically, lower HIV-1 DNA levels were associated with higher frequencies of cytotoxic and adaptive-like natural killer (NK) cell subsets, whereas faster HIV-1 DNA decay was linked to restored HIV-specific CD4+ and CD8+ T-cell responses during treatment. Notably, transcriptomic analyses uncovered divergent gene expression signatures related to B cell-associated immunity and type I interferon pathways, with individuals with higher HIV-1 DNA levels exhibiting elevated expression of immunoglobulin and interferon-stimulated genes, while faster decay correlated with enrichment of antiviral and complement-related genes. Collectively, these findings provide a preliminary characterization of immune correlates of peripheral blood total HIV-1 DNA dynamics in the early phase following ART initiation. This work offers potential immune clues for exploring the viral reservoir and generates testable hypotheses for validation in future large cohorts. Full article
(This article belongs to the Topic The Pathogenesis and Treatment of Immune-Mediated Disease)
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15 pages, 1210 KB  
Article
Factors Associated with Virological Non-Suppression Among People Living with HIV Receiving Antiretroviral Therapy in Kazakhstan: A National Registry-Based Study
by Anel Ibrayeva, Zhamilya Nugmanova, Anarkhan Nurkerimova, Aigerim Alimbekova, Marat Tukeyev, Alfiya Denebaeva, Jack DeHovitz, Yerlan Ismoldayev, Bolat Sadykov, Shynar Tanabayeva and Ildar Fakhradiyev
Trop. Med. Infect. Dis. 2026, 11(6), 156; https://doi.org/10.3390/tropicalmed11060156 - 9 Jun 2026
Viewed by 446
Abstract
Background: Virological suppression is a key outcome of antiretroviral therapy. Despite progress in HIV treatment in Kazakhstan, virological non-suppression remains a relevant clinical and public health issue requiring further analysis. This study aimed to assess the prevalence of virological suppression (VS) and [...] Read more.
Background: Virological suppression is a key outcome of antiretroviral therapy. Despite progress in HIV treatment in Kazakhstan, virological non-suppression remains a relevant clinical and public health issue requiring further analysis. This study aimed to assess the prevalence of virological suppression (VS) and to identify factors associated with the absence of VS among people living with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy (ART) in Kazakhstan. Methods: A retrospective cross-sectional analytical study was conducted using secondary analysis of a de-identified national registry database of people living with HIV (PLHIV) receiving ART in the Republic of Kazakhstan as of 30 September 2025. The primary outcome was virological non-suppression (VNS), defined as the last viral load (VL) value of at least 200 copies per milliliter. The analysis included sex, age, presumed route of HIV transmission, the first available cluster of differentiation 4 (CD4) cell count recorded in the registry, the last recorded percentage category of adherence to ART, and the aggregated category of ART regimen. The main descriptive, bivariate, and multivariable analyses were performed using a complete-case approach. Independent associations were assessed using multivariable logistic regression, and the results were presented as adjusted odds ratios (aORs) with 95 percent confidence intervals (CIs). Results: The initial registry extraction included 33,614 records, of which 32,130 patients were included in the final analytical sample. VS was achieved in 29,454 (91.7%) patients, whereas VNS was observed in 2676 (8.3%) patients. In the multivariable model, higher adjusted odds of VNS were observed among men compared with women (aOR 1.14; 95% CI 1.02–1.26), as well as among patients with a first CD4 count < 200 cells/μL compared with those with a first CD4 count of ≥500 cells/μL (aOR 1.25; 95% CI 1.09–1.44). The strongest association was found for reduced adherence to therapy. Compared with adherence of at least 95%, the adjusted odds of VNS were markedly higher among patients with adherence of 85–94% (aOR 28.66; 95% CI 25.85–31.77) and among those with adherence below 85% (aOR 61.05; 95% CI 50.50–73.81). In all age groups older than 25 years, the adjusted odds of VNS were lower than among patients younger than 25 years. Lower adjusted odds of VNS were also observed among patients with homosexual transmission, vertical transmission, and other or unspecified transmission routes compared with heterosexual transmission. Among ART regimens, regimens containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) were associated with lower adjusted odds of VNS than dolutegravir-containing regimens (DTG-containing regimens) (aOR 0.68; 95% CI 0.52–0.88), whereas no statistically significant differences were identified for regimens containing protease inhibitors (PIs). Conclusions: Despite the high overall level of VS among PLHIV receiving ART in Kazakhstan, VNS remains concentrated in clinically and programmatically important subgroups. It was most strongly associated with reduced adherence and was also associated with younger age, marked baseline immunosuppression, and male sex in the primary model. These findings support the need for targeted interventions focused on adherence support, early diagnosis, and differentiated long-term follow-up of patients. Full article
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26 pages, 3691 KB  
Review
The Gut Microbiome in HIV Pathogenesis: Interconnections Between Dysbiosis, Immune Dysfunction, and Viral Persistence
by Hossein Mardnaybin, Mehmet Demirci and Hayriye Kirkoyun Uysal
Int. J. Mol. Sci. 2026, 27(11), 4830; https://doi.org/10.3390/ijms27114830 - 27 May 2026
Viewed by 612
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Host–Microorganism Interaction)
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37 pages, 967 KB  
Review
Temporal Evolution of Drug Resistance to HIV Integrase Inhibitors
by Indrani Choudhuri, Jocelyn G. Olvera, Avik Biswas, Allan Haldane, Ronald M. Levy and Dmitry Lyumkis
Viruses 2026, 18(5), 540; https://doi.org/10.3390/v18050540 - 8 May 2026
Viewed by 1480
Abstract
HIV-1 integrase (IN) strand transfer inhibitors (INSTIs) are central to modern antiretroviral therapy (ART) because of their high potency and durable effect on viral suppression. However, drug resistance mutations (DRMs) within HIV-1 IN emerge, which can compromise long-term treatment efficacy. Many distinct DRMs [...] Read more.
HIV-1 integrase (IN) strand transfer inhibitors (INSTIs) are central to modern antiretroviral therapy (ART) because of their high potency and durable effect on viral suppression. However, drug resistance mutations (DRMs) within HIV-1 IN emerge, which can compromise long-term treatment efficacy. Many distinct DRMs that arise under INSTI therapy have been extensively tabulated in public repositories and literature. However, the timelines over which they emerge, accumulate, and consolidate in patients have not been systematically integrated across clinical and experimental studies. In this review, we synthesize current evidence on the temporal evolution of DRMs within HIV-1 IN by examining mutational kinetic data from viruses derived from people living with HIV/AIDS (PLWH) and from in vitro selection experiments. We compare experimental timelines to recent computational predictions derived from Potts-based fitness landscapes coupled with kinetic Monte Carlo simulations and identify reproducible kinetic classes that distinguish fast-, intermediate-, and slow-emerging DRMs. Rapidly emerging DRMs such as E92Q and N155H typically appear early under drug pressure and often represent low-barrier adaptive responses, whereas the most clinically consequential mutations, such as Q148H/K/R, G140A/S, and E138K, arise only after extended therapy and generally require compensatory mutational backgrounds to persist. Although absolute emergence times vary substantially between in vivo and in vitro systems, consistent temporal trends across datasets support the existence of underlying epistatic constraints that shape drug resistance evolution. Understanding DRM timelines is clinically relevant because it provides a framework for interpreting resistance detected at virological failure, informs optimal timing of resistance testing, and may enable earlier identification of high-risk evolutionary trajectories before durable resistance is established. Full article
(This article belongs to the Special Issue 15-Year Anniversary of Viruses)
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17 pages, 932 KB  
Systematic Review
Clinical Presentation, Etiology, and Outcomes of HIV-Associated Cardiomyopathy: A Systematic Review of Published Case Reports
by Omar Hozayen, Joseph Hozayen, Benjamin J. Behers, Anas Abu Jad, Bashar Roumia, Matthew W. Miller, Christoph A. Stephenson-Moe, Nicolas Riveros, Manuel Rosario and Karen M. Hamad
Viruses 2026, 18(5), 510; https://doi.org/10.3390/v18050510 - 29 Apr 2026
Viewed by 1779
Abstract
HIV-associated cardiomyopathy is a significant cause of morbidity and mortality among people living with HIV, contributing to heart failure, arrhythmia, and sudden cardiac death. Despite its clinical importance, its individual-patient clinical spectrum has not been systematically synthesized. We conducted a systematic review of [...] Read more.
HIV-associated cardiomyopathy is a significant cause of morbidity and mortality among people living with HIV, contributing to heart failure, arrhythmia, and sudden cardiac death. Despite its clinical importance, its individual-patient clinical spectrum has not been systematically synthesized. We conducted a systematic review of published English-language case reports and small case series describing cardiomyopathy in HIV-infected individuals. Etiologies were classified using a framework distinguishing cardiomyopathy arising from uncontrolled HIV from that occurring despite virologic control. Stratified analyses examined temporal trends and geographic differences. We identified 99 patients (75 male, 20 female, 4 unspecified) from 27 countries (80% high-income). Median age was 35 years (IQR 28–45). Among 52 patients with CD4 data, median was 154 cells/µL (IQR 84–391); 52% had CD4 < 200. Systolic dysfunction was present in 94% with echocardiographic data. Uncontrolled HIV phenotypes predominated (64%), but controlled phenotypes (21%)—including drug-induced cardiomyopathy (n = 19, predominantly zidovudine-associated) and autoimmune or inflammatory mechanisms (n = 13)—were substantial. Mortality declined across eras: 65% pre-ART, 32% early ART, 21% modern ART. Recovery occurred in 58%. HIV-associated cardiomyopathy is heterogeneous with improving outcomes across treatment eras. Systematic etiologic evaluation is warranted in all affected patients. The near absence of data from sub-Saharan Africa represents a critical gap. Full article
(This article belongs to the Special Issue HIV in the Context of Chronic Disorders and Aging)
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20 pages, 1678 KB  
Article
Epidemiological Characteristics and Treatment Outcomes of Drug-Resistant Tuberculosis in Limpopo Province, South Africa (2020–2024)
by Ivy Rukasha and Kabelo Gabriel Kaapu
Trop. Med. Infect. Dis. 2026, 11(4), 100; https://doi.org/10.3390/tropicalmed11040100 - 13 Apr 2026
Viewed by 981
Abstract
Background: Drug-resistant tuberculosis (DR-TB) continues to pose a major challenge in Limpopo Province, a predominantly rural region of South Africa with high prevalence of HIV and mobility of the cross-border population. Despite the scale-up of short all-oral bedaquiline-based regimens, there is limited [...] Read more.
Background: Drug-resistant tuberculosis (DR-TB) continues to pose a major challenge in Limpopo Province, a predominantly rural region of South Africa with high prevalence of HIV and mobility of the cross-border population. Despite the scale-up of short all-oral bedaquiline-based regimens, there is limited recent provincial evidence describing DR-TB epidemiological characteristics and treatment outcomes in the post-COVID-19 period. This study aimed to assess resistance patterns, treatment outcomes, and factors associated with unfavorable outcomes among patients with DR-TB in Limpopo Province from 2020 to 2024. Methods: A retrospective cohort study was conducted using routinely collected data from the Electronic Drug Resistant Tuberculosis Register (EDRWeb). All laboratory-confirmed DR-TB cases diagnosed between January 2020 and December 2024 were included. Descriptive statistics were used to summarize demographic and clinical characteristics. Multivariable logistic regression was performed to identify predictors of unfavorable outcomes (treatment failure, death, and loss to follow-up). Kaplan–Meier survival analysis was used to estimate survival probability following treatment initiation. Results: A total of 1240 DR-TB cases were recorded, of which 1165 (94%) had documented treatment outcomes. Rifampicin-resistant TB (RR-TB) predominated throughout the study period, accounting for 76% (951/1240) of cases and remaining stable over time. Treatment success improved from 173/260 (67%) in 2020 to 130/166 (78%) in 2024, while loss to follow-up declined from 34/260 (13%) to 4/166 (2%). Kaplan–Meier survival analysis showed that mortality occurred predominantly during the early phase of treatment. Patients receiving bedaquiline-containing regimens demonstrated significantly higher survival probability compared with those not receiving bedaquiline (log-rank p = 0.024; HR 0.58, 95% CI: 0.35–0.94). In multivariable analysis, HIV infection was independently associated with unfavorable outcomes (aOR 1.36; 95% CI: 1.04–1.77; p = 0.025), while increasing age showed a modest association with poorer outcomes. Conclusions: Treatment outcomes for DR-TB improved over the study period, accompanied by declining loss to follow-up and improved survival. The survival advantage observed among patients receiving bedaquiline-containing regimens supports continued prioritization of bedaquiline-based treatment strategies in DR-TB management. Strengthening access to these regimens, alongside integrated HIV care, may further improve treatment outcomes in Limpopo Province and similar high-burden settings in South Africa. Full article
(This article belongs to the Section Infectious Diseases)
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16 pages, 707 KB  
Article
Predictors of Treatment Outcomes Among HIV-Positive Patients with Drug-Resistant Tuberculosis in Rural Eastern Cape, South Africa: A Retrospective Cohort Study
by Thembile Zini, Urgent Tsuro, Lindiwe Modest Faye, Ncomeka Sineke and Monwabisi Faleni
Int. J. Environ. Res. Public Health 2026, 23(4), 474; https://doi.org/10.3390/ijerph23040474 - 9 Apr 2026
Viewed by 748
Abstract
Background: Drug-resistant tuberculosis (DR-TB) remains a major public health challenge in South Africa, particularly in rural settings with high HIV co-infection rates. Understanding predictors of treatment response among people living with HIV is essential for improving clinical management and programmatic outcomes. This study [...] Read more.
Background: Drug-resistant tuberculosis (DR-TB) remains a major public health challenge in South Africa, particularly in rural settings with high HIV co-infection rates. Understanding predictors of treatment response among people living with HIV is essential for improving clinical management and programmatic outcomes. This study aimed to identify socio-demographic and clinical predictors of treatment outcomes among HIV-positive individuals diagnosed with multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) in rural Eastern Cape Province, South Africa. Methods: A retrospective cohort study was conducted using routinely collected clinical records of DR-TB patients initiated on treatment between January 2020 and December 2024 at two public healthcare facilities. A total of 239 patients with complete treatment outcome data were included. Treatment outcomes were classified as favourable (cured or treatment completed) or unfavourable (death, treatment failure, or loss to follow-up). Descriptive statistics were used to summarise patient characteristics, while univariate and multivariable logistic regression analyses were performed to identify factors associated with treatment outcomes. Results: Most participants were aged ≤ 39 years (58%), male (60%), unemployed (90%), and without income (80%). MDR-TB accounted for 40% of cases, rifampicin-resistant-TB (RR-TB) for 53%, and XDR-TB for 7.1%. Multivariable analysis showed that XDR-TB was the strongest independent predictor of unfavourable treatment outcome (AOR = 0.18; 95% CI: 0.06–0.58; p = 0.004). Income status was also significantly associated with outcome, with participants reporting some incomes having lower odds of favourable outcomes (AOR = 0.46; 95% CI: 0.23–0.92; p = 0.036). The model demonstrated modest predictive performance (AUC = 0.67). Conclusions: These findings highlight the dominant influence of resistance phenotype, particularly XDR-TB, on treatment prognosis among HIV-positive DR-TB patients in rural Eastern Cape. Integrating early resistance profiling, intensified clinical management of XDR-TB, and socioeconomic support mechanisms may improve treatment outcomes in high-burden rural settings. Full article
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23 pages, 598 KB  
Review
Series 3: From Infection to Disease: A Global Scoping Review of Medical and Behavioural Determinants of Progression from TB Infection to TB Disease
by Sonia Menon, Anthony D. Harries, Riitta A. Dlodlo, Gisèle Badoum, Mohammed F. Dogo, Olivia B. Mbitikon, Pranay Sinha, Yan Lin, Jyoti Jaju, Aung Naing Soe, Anisha Singh, Bharati Kalottee and Kobto G. Koura
Trop. Med. Infect. Dis. 2026, 11(4), 94; https://doi.org/10.3390/tropicalmed11040094 - 2 Apr 2026
Viewed by 1544
Abstract
Background: Tuberculosis (TB) remains a major global health threat, particularly in low- and middle-income countries, with TB infection (TBI) serving as the primary source of TB disease. While HIV infection has long been recognised as a major risk factor for TB progression, the [...] Read more.
Background: Tuberculosis (TB) remains a major global health threat, particularly in low- and middle-income countries, with TB infection (TBI) serving as the primary source of TB disease. While HIV infection has long been recognised as a major risk factor for TB progression, the rise of Non-Communicable Diseases (NCDs), which may exert immunosuppressive effects, further compounded by their treatment, contributes to increased TB susceptibility. This scoping review synthesises evidence from systematic reviews on medical and behavioural risk factors for TBI progression to TB disease, for both asymptomatic and symptomatic disease. Methods: A preliminary literature search was conducted on 11 January 2025, in PUBMED using the keywords “tuberculosis,” “asymptomatic or subclinical tuberculosis” “risk factors,” and “systematic review” followed by targeted reviews on the identified medical and behavioural risk factors for TB infection progression to TB disease. Results: A total of 25 systematic reviews were included. Medical risk factors for progression from TB infection to TB disease included diabetes mellitus (DM), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), undernutrition (including iron and vitamin D deficiency), cancer—particularly haematological malignancies—and immunosuppressive therapies (TNF-α inhibitors and glucocorticoids). Iron and vitamin D deficiency, particularly severe deficiency, is linked to increased TB risk, especially among people living with HIV. Behavioural risk factors, including tobacco, drug, and alcohol use, were also highlighted. Geographic variations in TB prevalence, diagnostic practices, and healthcare systems contributed to differences in risk estimates across reviews. No systematic reviews were identified that examined risk factors for asymptomatic TB. Conclusions: The convergence of TB with NCDs, compounded by immunosuppressive therapies, poses a public health challenge in high TB burden settings. Effective TB prevention requires targeted screening, along with enhanced management of these NCDs. Nutritional support, particularly screening and treatment of anaemia and vitamin D deficiency, may benefit individuals with TBI, comorbid NCDs, and HIV. A multidisciplinary approach, integrating behavioural interventions and tailored prevention strategies, is essential to achieving WHO’s End TB targets. Addressing the evidence gap on risk factors for asymptomatic TB is also critical to improve early detection and interrupt transmission. Full article
(This article belongs to the Section Infectious Diseases)
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18 pages, 305 KB  
Article
Needs Assessment to Inform a Life Course-Based Support Programme for Adolescents with Perinatally Acquired HIV in Rural Limpopo, South Africa
by Rirhandzu Austice Mabasa, Cairo Bruce Ntimana, Tebogo Maria Mothiba and Linda Skaal
Int. J. Environ. Res. Public Health 2026, 23(4), 441; https://doi.org/10.3390/ijerph23040441 - 31 Mar 2026
Viewed by 804
Abstract
This study explored the challenges and support needs of adolescents identified as living with perinatally acquired HIV based on clinical history and early childhood treatment records to generate evidence that can inform the development of an adolescent-centred support programme. A mixed-methods, sequential exploratory [...] Read more.
This study explored the challenges and support needs of adolescents identified as living with perinatally acquired HIV based on clinical history and early childhood treatment records to generate evidence that can inform the development of an adolescent-centred support programme. A mixed-methods, sequential exploratory design was employed. In the qualitative phase, semi-structured interviews were conducted with 21 APHIV (mean age 15.5 years, range 12–19; 61.9% female) recruited from health facilities in rural Limpopo, South Africa. In the quantitative phase, a survey informed by qualitative findings was administered to 186 APHIV. Life Course Theory informed the conceptual framework of this study and guided the development of the interview guide as well as the interpretation of adolescents’ lived experiences. Data saturation was reached after twenty-one in-depth interviews. The qualitative analysis generated themes related to HIV/AIDS knowledge and support systems, which were subsequently interpreted through key Life Course Theory constructs, including time and place, agency, timing, and linked lives. The findings revealed that the life trajectories of older adolescents were more strongly shaped by the historical circumstances surrounding their HIV diagnosis and disclosure compared with those of younger adolescents. The results further highlighted gaps in treatment literacy, challenges in disclosure processes, emotional distress, and variability in family and health-care support. Most adolescents reported that their HIV-positive status was disclosed by someone other than their parents, while some discovered their status independently. The findings provide empirical evidence on informational, psychosocial, and support needs that can guide the design of adolescent-centred interventions for adolescents living with perinatally acquired HIV. This study recommends the development of context-specific, adolescent-centred support programmes that integrate psychosocial support, family engagement, and improved communication with healthcare providers to strengthen adherence and well-being among APHI. Full article
12 pages, 983 KB  
Article
Early Identification of Atherosclerosis in People Living with HIV by Coronary Computed Tomography Angiography
by Müge Toygar Deniz, Özgür Çakır, Burak Acar, Cemile Çakmak, Sibel Balcı and Sıla Akhan
Diagnostics 2026, 16(6), 893; https://doi.org/10.3390/diagnostics16060893 - 18 Mar 2026
Viewed by 555
Abstract
Background: The advancements in antiretroviral treatment (ART) have led to a 69% reduction in AIDS-related deaths. However, people living with HIV (PLWH) face age-related comorbitidies like coronary artery disease (CAD), which can be 50% higher compared to HIV-negative individuals. This study explores the [...] Read more.
Background: The advancements in antiretroviral treatment (ART) have led to a 69% reduction in AIDS-related deaths. However, people living with HIV (PLWH) face age-related comorbitidies like coronary artery disease (CAD), which can be 50% higher compared to HIV-negative individuals. This study explores the prevalence and extent of early CAD in PLWH without a history of cardiovascular disease using computed tomography angiography (CTA). Methods: A 320-detector row CTA (Aquilion ONE, Canon Medical Systems) was utilized to determine prevalence of coronary atherosclerosis. Logistic regression analysis and ROC analysis were performed to predict risk factors for the presence of atherosclerosis. Results: A total of 186 individuals participated in this study, including 74 PLWH and 112 HIV-seronegative controls. A notable disparity in the occurrence of coronary atherosclerosis was observed between the two groups, with 20% of individuals in PLWH showing plaque in the coronary arteries as detected by CTA, compared to 7% in the control group (p = 0.015). In the plaque group, a significant increase in age was observed (p = 0.001) along with elevated levels of fasting blood glucose and hemoglobin A1c (p < 0.001 and p = 0.017 respectively). HIV seropositivity and age were significantly associated with the presence of plaque (aOR, 5.5 [95% CI, 1.7–25.8] and 21.7 [95% CI, 5.5–88] respectively). When evaluating age, fasting blood sugar and HbA1c through ROC analysis to predict plaque presence, age is the strongest predictor, with an AUC of 0.899 (p < 0.001, 95% CI: 0.847–0.939) and a cutoff value of 35 years. Additionally, HbA1c and fasting blood sugar had an AUC of 0.664 (p = 0.0047, 95% CI: 0.574–0.746) and 0.759 (p < 0.001, 95% CI: 0.688–0.822) respectively. Youden cutoff values were 5.5 for HbA1c and 92.4 for fasting blood sugar. Conclusions: The higher prevalence of CAD in PLWH may indicate that inflammation is a substantial risk. It is important to remember that CAD can develop early in PLWH. Moreover, including HbA1c and fasting blood sugar measurements in routine follow-up may help facilitate earlier detection of atherosclerosis. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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40 pages, 834 KB  
Review
HIV Infection, Neurotoxicity, Inflammation, Premature Aging, and Therapeutic Challenges to PLWH: An Overview
by Mudit Tyagi, Ulhas Naik, Kratika Tyagi, Madhulika Sharma, Gagan Kaushal, Alok Bhushan, Michael Bukrinsky and Priya Tyagi
Int. J. Mol. Sci. 2026, 27(5), 2192; https://doi.org/10.3390/ijms27052192 - 26 Feb 2026
Cited by 6 | Viewed by 1835
Abstract
HIV infection remains a major global health challenge due to its complex pathogenesis and lifelong persistence in people living with HIV (PLWH). A central barrier to eradication is the virus’s ability to establish long-lived latent reservoirs in different tissues, including the central nervous [...] Read more.
HIV infection remains a major global health challenge due to its complex pathogenesis and lifelong persistence in people living with HIV (PLWH). A central barrier to eradication is the virus’s ability to establish long-lived latent reservoirs in different tissues, including the central nervous system (CNS), where it evades immune clearance and antiretroviral therapy (ART). These reservoirs, seeded early during infection, fuel viral rebound if ART is interrupted, requiring lifelong treatment. In the CNS, HIV persists despite systemic viral suppression because of limited ART penetration across the blood–brain barrier (BBB), and infection of long-lived cells such as microglia and perivascular macrophages. Although modern ART regimens significantly reduce viral burden and HIV-related morbidity, they do not eliminate neurocognitive complications. Suboptimal CNS drug penetration and certain ART-associated toxicities contribute to CNS dysfunction, persistent neuroinflammation, and accelerated aging of the brain. As PLWH now experience increased life expectancy, prolonged exposure to ART and persistent low-level viral activity exacerbate chronic inflammation, immune activation, and metabolic dysregulation, collectively accelerating neurobiological aging. These pathological processes contribute to the development of HIV-associated neurocognitive disorders (HAND), which affect nearly half of virally suppressed PLWH. This review examines HIV-associated inflammation, neurotoxic pathways, and accelerated aging in PLWH in the modern ART era. Full article
(This article belongs to the Special Issue HIV Infection, Pathogenesis and Treatment)
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