Search Results (7,394)

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

Adolescents living with HIV (ALHIV) face ongoing challenges with treatment adherence and engagement in care, resulting in lower viral suppression rates compared to adults. Peer navigation has shown promise in supporting psychosocial well-being and adherence among adults, but evidence specific to adolescents in sub-Saharan Africa (SSA) remains limited. This qualitative evidence synthesis (QES) describes and assesses the quality of qualitative and mixed-methods studies on peer navigation and support interventions for ALHIV receiving antiretroviral therapy in SSA. Eligible studies, published in English between January 2015 and October 2025, were identified through a comprehensive search strategy in PubMed, Scopus, CINAHL, and APA PsycArticles. Data were extracted and analyzed thematically using Atlas.ti, and aligned with the Context–Intervention–Mechanism–Outcome (CIMO) framework. PNs in the studies were young people living with HIV who provided education, counselling and adherence support to their peers who were ALHIV. Effective programmes featured structured training, supportive supervision, and flexible delivery models adapted to adolescents’ preferences. Mechanisms of change included trust-building, emotional support, disclosure coaching and empowerment. Reported outcomes included improved adherence, clinic attendance and various psychosocial indicators. However, challenges such as stigma, role ambiguity, limited remuneration, and lack of policy guidance constrained the sustainability and scalability of PN programs. Overall, peer navigation interventions appear effective in strengthening adolescent HIV care when PNs are adequately trained, supervised and contextually adapted. The variation in how peer navigation and support interventions for ALHIV are delivered and designed, along with the lack of standardization of the interventions, may affect the generalizability of the findings and the rollout of PN programs across SSA. Full article

Background: People living with HIV (PLWH) have a substantially increased risk of both AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs), which remain a major cause of morbidity despite effective antiretroviral therapy (ART); this review aims to integrate current epidemiological, molecular, and clinical evidence on HIV-associated oncogenesis. Methods: A structured literature search was conducted in PubMed (2000–2026) using predefined keywords, including “HIV”, “cancer”, “oncogenesis”, and “immune dysregulation”, with inclusion of original studies, systematic reviews, and meta-analyses meeting predefined quality criteria. Results: Available evidence indicates that HIV contributes to cancer development through both direct and indirect mechanisms: viral proteins such as Tat, Nef, and Vpr disrupt apoptosis, DNA repair, and cell cycle regulation, while chronic immune activation, persistent inflammation, and immunosuppression impair tumor immune surveillance and facilitate oncogenic viral co-infections, including Epstein–Barr virus, human papillomavirus, and human herpesvirus 8. Emerging pathways, such as epigenetic alterations, microRNA dysregulation, metabolic reprogramming, and the contribution of HIV reservoirs to pro-tumorigenic microenvironments, further modulate cancer risk. Conclusions: HIV may function as a cofactor that enhances the effects of oncogenic viruses by promoting viral persistence and immune dysregulation; while biologically plausible, direct evidence linking HIV to amplification of tumorigenesis in humans remains limited. Full article

Background/Objectives: People with HIV (PWH) remain at high risk for cardiovascular and metabolic complications despite effective antiretroviral therapy (ART). Diet quality is an important modifiable factor that may influence these complications. Diets high in ultra-processed foods (UPF) have been linked to adverse metabolic and inflammatory profiles in the general population, but their impact on PWH remains poorly understood. The NOVA 4 classification categorizes foods by degree of processing, from unprocessed/minimally processed (NOVA 1) to UPF (NOVA 4). Methods: We conducted a cross-sectional study of adults with virologically suppressed HIV on stable ART. Assessments included dietary intake consisting of 24 h recalls analyzed with Nutrition Data System for Research software (NDSR) and classified into NOVA categories by a registered dietitian and the following characteristics: body composition (total and regional fat by DEXA and CT scan abdomen), cardiometabolic variables (glucose, HbA1C, HOMA-IR, lipids, blood pressure), and biomarkers of inflammation, immune activation, and gut integrity quantified by ELISA. Patients were stratified into NOVA 4 groups based on the median and quartile proportions of total energy intake from NOVA 4 foods. Associations between dietary NOVA and outcomes were analyzed using generalized additive models (GAMs) adjusted for age, sex, race, and CD4 count. Results: Among 222 PWH (mean age 45.4 ± 14.2 years; 31% female; 66% non-white; BMI 30.61 ± 7.91 kg/m²), median NOVA 4 intake was 45.6% of total energy intake. Participants with higher vs. lower NOVA 4 intake showed differences in diet quality, but in GAMs, higher NOVA 4 intake was not associated with higher levels of inflammatory, cardiometabolic, gut integrity, and body composition variables. Conclusions: In PWH, UPF consumption was high but not associated with markers of cardiometabolic health, systemic inflammation, or gut integrity. This may reflect the multifactorial nature of the heightened inflammation in PWH, potentially obscuring the effect of diet. Full article

Background: People living with HIV (PLWH) constitute a vulnerable population during the COVID-19 pandemic; however, it remains uncertain whether long-term suppressive antiretroviral therapy (ART) restores sufficient immune competence to support robust hybrid immunity. While vaccination followed by breakthrough infection—termed hybrid immunity—typically elicits potent humoral responses in immunocompetent individuals, the functional quality and breadth of these responses against evolving Omicron subvariants remain poorly characterized in PLWH. This study aimed to assess functional antibody responses, including neutralizing activity and Fc effector functions, in vaccinated and unvaccinated PLWH who experienced breakthrough infection with Omicron subvariants BA.4/5 or BF.7. Methods: We enrolled three cohorts between December 5 and December 20, 2022: 25 HIV-negative individuals with breakthrough infection (BTI-HC), 20 ART-experienced PLWH with breakthrough infection following three-dose COVID-19 vaccination (BTI-HIV), and 10 ART-experienced PLWH with primary infection without prior vaccination (PI-HIV). All HIV-positive participants were receiving suppressive ART with regimens based on non-nucleoside reverse transcriptase inhibitors or integrase strand transfer inhibitors for a median of 3.4 years. We measured receptor-binding domain (RBD)-specific IgG, neutralizing antibody titers against ancestral D614G, Delta, BA.1, BA.4/5, BF.7, XDV, KP.2, and KP.3 variants, and antibody-dependent cellular cytotoxicity (ADCC) responses. Results: Despite lower absolute CD4⁺ T cell counts, BTI-HIV participants mounted RBD-binding IgG, neutralizing antibody, and ADCC responses that were comparable to BTI-HC and significantly exceeded PI-HIV across all tested variants. Both breakthrough infection cohorts exhibited immunological imprinting, with higher neutralizing titers against ancestral D614G than infecting BA.4/5 or BF.7 variants. Emerging variants XDV, KP.2, and KP.3 demonstrated substantial neutralization escape in all groups. PI-HIV showed markedly diminished neutralization breadth and failed to generate enough responses against all tested Omicron strains. Conclusions: Suppressive ART enables PLWH to mount hybrid immunity—conferred by vaccination followed by BF.7 or BA.4/5 breakthrough infection—with neutralizing and ADCC responses comparable to HIV-negative individuals, and significantly exceeding those of unvaccinated PLWH with primary infection. This underscores the critical role of vaccination in establishing effective hybrid immunity in this population. However, we observed immunological imprinting, with higher titers against ancestral strains than against infecting variants, and substantial escape by emerging sublineages XDV, KP.2, and KP.3 across all groups. These findings support prioritizing updated variant-containing vaccines for HIV-positive populations and reinforce the essential role of vaccination in this vulnerable group. Full article

Background/Objectives: Women and girls, particularly in sub-Saharan Africa, face high risks for both HIV and unintended pregnancy. Inconsistent condom use underscores the need for new multipurpose prevention technologies (MPTs) that combine HIV pre-exposure prophylaxis (PrEP) and contraception. Long-acting (LA) injectables are especially promising. To this end, an LA cabotegravir (CAB)/medroxyprogesterone acetate (MPA) in situ-forming implant (ISFI) has been developed. We report pharmacokinetic (PK) modeling to characterize CAB and MPA disposition and absorption to support the development of the MPT ISFI. Methods: Female BALB/c mice received single intravenous (IV) or subcutaneous (SQ) bolus doses of CAB or MPA. Sparse plasma samples were collected (~3 mice/timepoint) for PK analysis by LC-MS/MS. Noncompartmental analysis assessed SQ bioavailability. Macroparameterized compartmental PK models were fit to IV data to derive unit impulse responses (UIRs) for each drug. Results: CAB and MPA exhibited 61% and 42% bioavailability, respectively. CAB IV PK was best described by a two-compartment model with macroconstant parameters: A = 16,621 ng/mL, α = 4.52 h⁻¹, B = 30,206 ng/mL, and β = 0.053 h⁻¹. MPA IV PK was also best described by a two-compartment model, with A = 2506 ng/mL, α = 10.5 h⁻¹, B = 439 ng/mL, and β = 0.65 h⁻¹. These values define the UIR for CAB and MPA. Conclusions: Our IV PK modeling framework fully characterizes CAB/MPA disposition in mouse, enabling downstream deconvolution-based estimation of absorption from controlled-release formulations. This provides a foundation for in vitro–in vivo correlation, facilitating preclinical evaluation of long-acting formulations such as ISFIs. Full article

Background: Pre-eclampsia (PE) is a significant cause of maternal and perinatal morbidity and mortality globally and is characterized by impaired endothelial function and disturbances in coagulation pathways. The effects of Human Immunodeficiency Virus (HIV) on the immune and coagulation systems have been investigated during pregnancy, but there are few reports on anticoagulant factors in pregnant women who are infected with HIV and develop PE. This investigation compares plasma protein C levels in pregnant women with pre-eclampsia and those without pre-eclampsia, and compares the results based on their HIV status. Methods: A hospital-based cross-sectional study design was used for the current research, which was carried out at Charlotte Maxeke Johannesburg Academic Hospital, South Africa. A total of 83 pregnant women participated in the study and were categorized into one of four groups: normotensive HIV-negative (n = 36); normotensive HIV-positive (n = 18); pre-eclamptic HIV-negative (n = 21); and pre-eclamptic HIV-positive (n = 8). Data collected included demographic information and clinical characteristics that were abstracted from maternity records. Plasma protein C concentrations were determined by ELISA (enzyme-linked immunosorbent assay). Nonparametric statistical methods were used to compare the mean values of plasma protein C between each of the four groups, and significance was set at p < 0.05. Subgroup analyses, particularly for the pre-eclamptic HIV-positive group (n = 8), were considered exploratory due to small sample sizes. Results: As would be anticipated, both systolic and diastolic blood pressure values were significantly elevated in the pre-eclamptic group when compared to the normotensive control subjects (p < 0.0001). There were no statistically significant differences in plasma protein C concentration between the normotensive and pre-eclamptic groups, nor between the HIV-negative and HIV-positive groups. Similarly, there were no significant differences in plasma protein C concentration when comparing all four study groups (Kruskal–Wallis test p = 0.2295). Conclusions: Plasma protein C concentrations did not vary significantly according to the presence of pre-eclampsia or HIV status in this cohort. These findings suggest that protein C concentrations were not measurably altered between groups within this study population. However, due to the small sample size in key subgroups, these findings should be considered preliminary and interpreted with caution. Larger, adequately powered studies are required to further investigate potential associations between HIV infection, pre-eclampsia, and anticoagulant pathways during pregnancy. Full article

Objectives: The co-administration of Bruton’s tyrosine kinase (BTK) inhibitors with antiretroviral drugs is challenging due to potential drug–drug interactions (DDIs). However, clinical trials specifically assessing such DDIs are lacking. We aimed to evaluate DDIs between the BTK inhibitors ibrutinib, zanubrutinib and acalabrutinib with representative antiretroviral drugs and to provide dose adjustment strategies using physiologically based pharmacokinetic (PBPK) models. Methods: PBPK models were developed in PK-Sim software. Model performance was verified by comparing simulated pharmacokinetic parameters and DDI magnitudes with probe drugs (midazolam or maraviroc) with reported clinical data. The validated models were subsequently applied to assess DDIs and explore dose adjustment strategies. Results: The developed PBPK model accurately describes the pharmacokinetics of each drug. Darunavir/ritonavir substantially increased the maximum plasma concentration (C_max) of ibrutinib, zanubrutinib, and acalabrutinib by 496%, 312%, and 160%, respectively. In contrast, efavirenz reduced C_max by 43%, 33%, and 37%, respectively, while etravirine caused smaller decreases of 5%, 0%, and 10%. Based on these predictions, recommended dose adjustment strategies include ibrutinib 105 mg once daily, zanubrutinib 40 mg twice daily, and acalabrutinib 50 mg twice daily when co-administered with darunavir/ritonavir or ibrutinib 980 mg once daily, zanubrutinib 240 mg twice daily, and acalabrutinib 150 mg twice daily when co-administered with efavirenz. No dose adjustment is required with etravirine. Conclusions: The PBPK models accurately predicted the in vivo pharmacokinetics of ibrutinib, zanubrutinib, acalabrutinib, and those of the antiretrovirals darunavir/ritonavir, efavirenz, and etravirine, and the DDIs between them. The dose adjustment strategies provided information valuable to the optimization of antineoplastic therapy in HIV-related lymphoma (HRL) patients. Full article

Six 1,4-disubstituted pyrazoles linked to a benzenesulfonamide and a benzodioxane unit have been synthesized through a copper(I)-catalyzed formal [3+2] cycloaddition (32CA) reaction of alkynes with 3-arylsydnones. The Cu-catalyzed sydnone–alkyne cycloaddition (CuSAC) procedure has been optimized to promote the formation of the pyrazole ring and to deliver in three steps the six target compounds 5a–f, fully characterized by ¹H/¹³C-NMR and mass spectrometry (EIMS). Ten solvent conditions were evaluated. The reaction proceeded most efficiently in the presence of copper(II) sulfate pentahydrate in aqueous t-butanol in the presence sodium acetate, to reach a yield of 96%. The mechanism of the Cu(I)-catalyzed reaction has been studied within the Molecular Electron Density Theory (MEDT). This rection is a domino process that consists in a Cu(I)-catalyzed formal [3+2] cycloaddition followed of an extrusion of CO₂ yielding the final pyrazole. The capacity of heterocyclic compounds 5a–f to interact with human cyclophilin A (Cyp A), which is a host cofactor for hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1), and with the HIV-1 protein gp120-CD4 was evaluated using molecular docking. Compounds 5a,b,d,f showed a satisfactory protein binding capacity. The physicochemical and metabolic properties of the compounds were also evaluated in silico. These predictions provide important information to guide future design in this series of potential antiviral agents. Full article

Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms capable of causing diverse clinical manifestations. Their epidemiology among people with HIV remains insufficiently characterized. This study examined the epidemiology of NTM among people with HIV admitted to the Hospital for Infectious Diseases in Warsaw between 2017 and 2023. Data on CD4+ T-cell counts, type of NTM involvement, species identification, and antimicrobial resistance were obtained from medical records. In the analyzed group the median of the CD4+ T-cell count was 25 cells/mm³ (IQR 65 cells/mm³). Late HIV diagnosis was observed in n = 45/50 (90.0%) patients. NTM colonization was identified in n = 20 (33.9%) patients, while n = 39 (66.1%) had active NTM disease, including pulmonary (53.9%), disseminated (41.0%), and extrapulmonary (5.1%) forms. Mycobacterium kansasii was the most common species among colonized patients, n = 7/24 (29.2%), whereas Mycobacterium avium predominated among patients with NTM disease, n = 30/42 (71.4%). Among patients with NTM disease, in vitro resistance to at least one antimicrobial agent was observed in 80.0% of M. avium isolates. High levels of resistance of M. avium were noted for ethambutol (n = 8/8, 100%), moxifloxacin (n = 16/22, 72.8%) and linezolid (n = 9/21, 42.9%). Proper identification of Mycobacterium species and its antibiotic resistance might be helpful in selecting effective antimicrobial therapy. Early HIV diagnosis is needed to prevent NTM disease. Full article

In recent years, fractional HIV models have received increasing attention. This study derives a fractional HIV model using the continuous-time random walk (CTRW) method, endowing the mathematical model with physical significance. Based on the transmission characteristics of HIV, the proposed model considers extrinsic infectivity, intrinsic infectivity, and drug control, specifically as follows: the extrinsic infectivity is a constant independent of the infection time; the intrinsic infectivity is a power-law function that depends on drug efficacy and infection time; the drug efficacy rate follows a Mittag–Leffler distribution with a long-term effect. Based on these considerations, a fractional HIV model with drug control is established in this paper. In addition, the global asymptotic stability of the equilibrium and the sensitivity analysis of the basic reproduction number $R_0$ are studied, and the theoretical results are verified by numerical simulations. The results show that reducing extrinsic infectivity, controlling intrinsic infectivity, and the drug efficacy rate are crucial in controlling the spread of HIV. Full article

Allogeneic hematopoietic cell transplantation (HCT) has been used for decades to treat certain malignant and non-malignant hematological conditions, but challenges remain. Increased understanding of disease mechanisms and recent developments in genome editing have enabled alternative strategies utilizing gene-edited autologous HCT and many of these have progressed to the clinic. We present here a comprehensive review of clinical trials of gene-edited autologous hematopoietic stem cells for the treatment of hemoglobinopathies and immunodeficiencies. Searches of major international clinical trial registries were carried out using specific key words. In total, 44 interventional clinical trials investigating gene-edited autologous stem cell therapies were identified, with CASGEVY (exagamglogene autotemcel) being the only product approved to date. Hemoglobinopathies were the most common indication (n = 37) followed by immunodeficiencies (n = 4), with single trials in HIV-1 infection, pyruvate kinase deficiency and limb–girdle muscular dystrophy. Gene-editing strategies fall into three categories: disruption of the BCL11A erythroid enhancer, editing of the γ-globin promoter and direct correction or disruption of disease-relevant genes. CD34⁺ hematopoietic stem and progenitor cells are the most common cell types edited, and CRISPR-Cas9 is the most widely used gene-editing modality. While results are encouraging, efficient intracellular delivery of gene-editing tools, editing efficiencies and off-target editing remain challenges for the field. Full article

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

Our community-based participatory research (CBPR) partnership convened an in-person, bilingual empowerment theory-based community forum to disseminate and translate findings from our trial of Nuestra Comunidad Saludable (Our Healthy Community), a multilevel intervention designed to improve uptake of COVID-19 testing and vaccination among Spanish-speaking Latine communities in North Carolina. The forum brought together community members, healthcare providers, organizational representatives, and academic researchers from across North Carolina. Drawing on findings from the intervention trial, participants engaged in facilitated, structured dialogue to identify community priorities and generate recommendations to advance health equity among Latine communities. Thirty-six participants identified eight priorities: (1) reducing health service gaps and inequities exposed by COVID-19; (2) expanding access to bilingual, culturally responsive mental health services; (3) improving understanding of HIV prevention and treatment; (4) strengthening services for children with disabilities; (5) protecting immigrant rights and ensuring safe access to services; (6) increasing political and social support for Latine health; (7) improving access to trusted, culturally responsive providers and community organizations; and (8) addressing social determinants of health, including employment, housing, and food security. The empowerment-based forum identified community priorities, challenges, and recommendations that can inform practice, intervention, policy, and research, and advance health equity for Spanish-speaking Latine communities. Full article

Despite effective antiretroviral therapy, HIV persists in diverse tissue reservoirs that pose major barriers to a cure. This review examines the heterogeneous maintenance mechanisms of HIV reservoirs in lymph nodes, intestinal mucosa, and the central nervous system (CNS). It analyzes how distinct tissue microenvironments—including immune-privileged niches, specialized cellular subsets, and local signaling networks—govern viral persistence and latency. Lymph nodes function as a dynamic hub interconnected with systemic reservoirs; the intestinal mucosa represents a site shaped by barrier integrity, microbial translocation, and mucosal immunity; the CNS constitutes a compartmentalized sanctuary protected by the blood–brain barrier. The review further discusses tissue-specific antiretroviral drug penetration and targeted clearance strategies, providing a foundation for developing multi-site intervention approaches toward HIV cure. Full article