Human Immunodeficiency Virus Research Articles

Optimizing rosemary oil nanoemulsion loaded with nelfinavir and epigallocatechin gallate: A Design Expert® endorsed approach for enhanced neuroAIDS management

This study focuses on optimizing the delivery of Nelfinavir (NFV), a vital protease inhibitor in antiretroviral therapy, and Epigallocatechin gallate (EGCG), a potent adjunctive anti- human immunodeficiency virus (anti-HIV) agent found in green tea. The challenge lies in NFV's low intrinsic dissolution rate, significant p-gp efflux, and high hepatic metabolism, necessitating frequent and high-dose administration. Our objective was to develop a nanoemulsion loaded with NFV and EGCG to enhance oral delivery, expediting antiretroviral effects for NeuroAIDS treatment. After meticulous excipient screening, we selected Tween 40 as the surfactant and polyethylene glycol 400 (PEG 400) as the co-surfactant. Employing a Quality by Design (QbD) approach with statistical multivariate methods, we optimized the nanoemulsion that exhibited a droplet size of 83.21 nm, polydispersity index (PDI) of 2.289, transmittance of 95.20 %, zeta potential of 1.495 mV, pH of 6.95, refractive index of 1.40, viscosity of 24.00 ± 0.42 mPas, and conductivity of 0.162 μS/cm. Pharmacokinetic studies demonstrated superior in vivo absorption of the optimized nanoemulsion compared to NFV and EGCG suspension. The optimized nanoemulsion showcased higher Cmax of NFV (9.75 ± 1.23 μg/ml) and EGCG (27.7 ± 1.22 μg/ml) in the brain, along with NFV (26.44 ± 1.44 μg/ml) and EGCG (313.20 ± 5.53 μg/ml) in the plasma. This study advocates for the potential of NFV and EGCG-loaded nanoemulsion in combination antiretroviral therapy (cART) for effective NeuroAIDS management.

Impact of CCR5Δ32 on the risk of infection, Staphylococcus aureus carriage, and plasma concentrations of chemokines in Danish blood donors

The CC chemokine receptor 5 (CCR5) is a suggested receptor for Staphylococcus aureus leukotoxin ED. Homozygosity for the Δ32 deletion (CCR5Δ32) protects against human immunodeficiency virus infection and possibly also against leukotoxin ED. We examined the impact of CCR5Δ32 on the susceptibility to S.aureus infection, all-cause infections, and S.aureus nasal carriage, respectively, and on the concentrations of circulating chemokines in blood donors. We included 95,406 participants from the Danish Blood Donor Study (DBDS) genotyped for >650,000 single nucleotide polymorphisms. The CCR5Δ32 (rs333, MAF: 0.12) was imputed from a reference panel and validated. Infectious outcomes were identified by diagnosis codes and redeemed prescription of antibiotics in national health registers. Data on S.aureus nasal carriage and forty-seven inflammatory biomarkers were available for 6721 and 7811 participants, respectively. Cox, logistic, and linear regression models adjusted for relevant confounders were used to explore said associations. During more than 700,000 person-years of observation, we found that CCR5Δ32 was associated with neither an increased risk of redeemed dicloxacillin, hospital-treated S.aureus-associated infection (replicated in 345,996 Icelanders), redeemed antibiotics, all-cause infection, and nor with S.aureus nasal carriage. We discovered an association between CCR5Δ32 and elevated CCL4 concentrations, which were 1.26-fold higher in Δ32-heterozygotes (95%-CI: 1.23-1.30) and 2.64-fold higher in Δ32-homozygotes (95%-CI: 2.41-2.90) compared with wildtype homozygotes. Conversely, concentrations of CCL2, CXCL-10, and CCL11 were slightly lower among Δ32-heterozygotes. Results from this CCR5Δ32 high-prevalent cohort do not support the idea that CCR5Δ32 affects the risk of S.aureus carriage or infection to any relevant degree, in this northern European context. CCL4 was the main chemokine affected by CCR5Δ32 and was observed in higher concentration among Δ32-carriers. This study cannot rule out that S.aureus is a previous driver of CCR5Δ32 selection. The Health Research Fund of Central Denmark Region, Aarhus University, Danish Administrative Regions, Bio- and Genome Bank Denmark, Danish Blood Donor Research Foundation, Aase & Ejnar Danielsens Foundation, Højmosegård Grant, National Institute of Allergy and Infectious Diseases, and A.P. Møller Foundation for the Advancement of Medical Science.

CMV Retinitis in the Context of SARS-CoV-2 Infection: A Case Study and Comprehensive Review of Viral Interactions

Purpose: Cytomegalovirus (CMV) retinitis is a sight-threatening condition predominantly affecting immunocompromised individuals, such as those with Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS). We aimed to present an observational case report on CMV retinitis following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and to review the literature on the molecular and cellular changes in CMV and SARS-CoV-2 infections and how they may influence each other. Case Description: A 32-year-old man with a history of AIDS presented with decreased vision and ocular pain exacerbated by movement, beginning a day prior. Ocular examination revealed anterior uveitis, corneal endothelial edema, and retinal necrosis in the left eye. CMV retinitis was diagnosed based on positive serologic testing and a low cluster of differentiation 4 (CD4) count, with concurrent SARS-CoV-2 infection detected. Treatment included valganciclovir and topical agents, with a focus on managing CMV complications. This case highlights the potential role of SARS-CoV-2 in reactivating dormant CMV in severely immunocompromised individuals. We also discuss the implications of this interaction for immunocompromised patients, emphasizing the need for vigilant monitoring and personalized treatment strategies. Conclusions: Our case suggests that SARS-CoV-2 may trigger reactivation of CMV infection, leading to bilateral involvement in patients with low CD4 lymphocyte counts, which can result in severe visual impairment. The review discusses the molecular and cellular interactions between CMV and SARS-CoV-2, as well as risk factors, pathophysiology, and diagnostic methods for CMV retinitis, providing recommendations based on the literature findings.

HIV is associated with subtle impairments in left ventricular function: insights from a large prospective cohort study of well-treated people with HIV

Abstract Background Human Immunodeficiency Virus (HIV) has become a treatable, chronic condition, but people with HIV still face an elevated risk of cardiovascular disease, including heart failure. Purpose To assess echocardiographic alterations in left ventricular (LV) function in a contemporary cohort of well-treated people with HIV compared to the general population. Methods We included 744 people with HIV frequency matched 1:1 on age and sex with controls from the general population. Both people with HIV and controls underwent echocardiography, physical examination, questionnaires and blood sampling according to similar study protocols. LV systolic dysfunction was defined as LV ejection fraction (LVEF) <50% or absolute global longitudinal strain (GLS) <16%. LV diastolic function was defined as abnormal if the following was true for half or more available parameters: (1) average E/e’>14, (2) septal e’ velocity < 7 cm/s or lateral e’ velocity <10cm/s, (3) tricuspid regurgitation velocity >2.8 m/s, (4) left atrial volume index >34ml/m2. Associations between HIV status and LV function were assessed using linear and logistic regression models adjusted for age, sex, smoking, hypertension, diabetes mellitus, total cholesterol and high-sensitivity C-reactive protein. Among people with HIV, the association between HIV-specific characteristics and LV function were assessed using logistic regression models with adjustment for the same potential confounders. Results Mean age was 53.4 years and 88% were male. For people with HIV, median time since HIV diagnosis was 18 years and 99% received antiretroviral therapy. People with HIV had lower adjusted mean absolute GLS [17.6 vs. 18.5%, p<0.001], E/A ratio [1.0 vs. 1.2, p<0.001] and average e’ [9.5 vs. 10.5 cm/s, p<0.001] than controls, while LVEF and E/e’ were not significantly different between people with HIV and controls (Figure 1). HIV was associated with impaired systolic function as assessed by GLS [odds ratio 1.70, 95% CI: 1.17-2.46, p=0.005], but not when assessed by LVEF [odds ratio 1.06, 95% CI: 0.78-1.45, p=0.69](Figure 2). Living with HIV was not associated with diastolic dysfunction compared to controls [odds ratio 0.97, 95% CI: 0.61-1.52, p=0.88], but longer HIV-duration was associated with higher odds of diastolic dysfunction among people with HIV (odds ratio 1.06, 95% CI: 1.02-1.10 per year, p=0.004). Current antiretroviral medication type, previous AIDS defining conditions, current CD4+ count and detectable viral load were not associated with LV dysfunction. Conclusion People with HIV show signs of early impairments in longitudinal LV systolic function compared to the general population. These subclinical changes may underlie the increased risk of heart failure observed in PWH.

Influence of disturbed blood flow on endothelial function in people living with HIV

Abstract Introduction People infected with human immunodeficiency virus (HIV) are more susceptible to endothelial dysfunction due to the virus itself, side effects of the antiretroviral therapy and classical risk factors. Endothelial damage is most prominent at the locations where laminar blood flow is disturbed and oscillatory shear stress with retrograde blood flow is dominating. Purpose The goal of this study was to assess the endothelial function in people with HIV, and to determine whether their endothelium is more susceptible to a short-term increase in retrograde blood flow in comparison to healthy individuals. Methods The study included 62 people with HIV infection and 38 people without HIV infection, in whom endothelial function was assessed using flow-mediated dilatation, which was presented in absolute (FMD) and relative (FMD%) values. The intervention produced oscillatory shear stress and retrograde blood flow during 20 minutes, after which the endothelial function assessment was repeated. Results Baseline FMD (0.30±0.07 vs. 0.36±0.07 mm; p<0.05) and FMD% (6.84±1.57 vs. 7.89±1.19 %, p<0.05) were lower in the HIV group in compare to controls. FMD and FMD% decreased in the HIV group by 0.03 mm and 0.7% (p<0.05), while in the control group they decreased by 0.09 mm and 2.0% (p<0.05). The post-intervention FMD and FMD% were not different between the groups (p>0.05). Conclusion People with HIV infection express worse endothelial function in compare to healthy individuals. Retrograde blood flow and oscillatory shear stress deteriorate endothelial function in both HIV patients and healthy controls, although this decline is more pronounced in healthy individuals.

PCSK9 inhibitors in HIV patients with dyslipidemia

Abstract Introduction Cardiovascular disease has become increasingly prevalent in the HIV (human immunodeficiency virus) population. Antiretroviral therapy and HIV itself independently increase the risk of dyslipidemia. While statins are currently the predominant therapy to treat dyslipidemia in HIV patients, drug-drug interactions and adverse drug events can limit their use. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a naturally occurring inhibitor of the LDL-receptor pathway. PCSK9 inhibitors offer an alternative in patients who cannot tolerate or need additional therapy in addition to statin for optimal dyslipidemia management. Purpose The purpose of this study is to compare major adverse cardiovascular events in HIV patients on a PCSK9 inhibitor (evolucumab, alirocumab, inclisiran) vs patients not on a PCSK9 inhibitor. Methods A retrospective cohort study was conducted using electronic medical records from a global federated health research network. The TriNetX network was searched on February 10, 2024, including records from 2020 to 2024. Patients were included based on a diagnosis of HIV status and concomitant dyslipidemia. Patients with HIV and dyslipidemia on a PCSK9 inhibitor were propensity-score matched for age, sex, race, and comorbidities with patients who were not on a PCSK9 inhibitor. The outcomes were mortality, myocardial infarction, heart failure and stroke. Results A total of 485 patients were included in the study. PCSK9 inhibitor use associated with 9% lower odds of all-cause mortality (odds radio, .29; 95% CI, 0.18-0.48; p<.0001). PCSK9 inhibitor use was also associated with 8% lower odds of heart failure (odds radio, .63; 95% CI, 0.47-0.85; p<.0023). No significant associations were noted for myocardial infarction (odds radio, .87; 95% CI, 0.63-1.21; p=0.406) or stroke (odds radio, .67; 95% CI, 0.45-1.01; p=0.052). Conclusion The role of dyslipidemia in HIV is challenging due the complex pathophysiology of HIV. There is an apparent increased risk of cardiovascular disease from the infection itself as well current antiretroviral therapies. While current guidelines recommend the use of statins as first line therapy for dyslipidemia in this population, the drug-drug interaction of statins with ARTs, as well as their side effects, limit their use at times. PCSK9 inhibitors are associated with lower odds of all-cause mortality and heart failure. No significant association was seen for myocardial infarction or stroke. They should be considered as an early intervention alongside statins in HIV patients with dyslipidemia. Further research should be done for the long term safety and tolerance of this therapy as well as cost-effectiveness and access to PCSK9 inhibitors in this population.

Thrombus aspiration in people living with HIV- a night mare for interventionist

Abstract Background Cardiovascular disease, particularly atherosclerosis, and its complications are a growing cause of morbidity and mortality among individuals living with human immunodeficiency virus (HIV) in the post-antiretroviral therapy era. The role of thrombus aspiration combined with primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) within this population remains contentious. While PCI is the preferred strategy for immediate revascularization in acute STEMI, challenges persist, with about 30% of patients experiencing persistent chest pain and ST-segment elevation despite achieving TIMI III flow in the culprit vessel. Methods We conducted a prospective observational study spanning from January 2015 to September 2023, involving ten consecutive HIV-infected patients presenting with STEMI to our acute coronary care unit. The study encompassed an analysis of baseline clinical characteristics, response to fibrinolytic therapy, angiographic findings, thrombus aspiration using the Export Aspiration Catheter, and the outcomes of percutaneous coronary intervention (PCI). Patients were closely monitored for in-hospital outcomes and followed up for five years, during which they received adjuvant highly active antiretroviral therapy (HAART). Results The mean age of the patients was 46 years, lower than their uninfected counterparts. Most patients presented with a lower Killip class, indicating favorable outcomes. CD4 count distribution showed variability, with ten patients undergoing rescue angioplasty with thrombus aspiration using the Export Catheter. The cohort was followed for five years, receiving consistent HAART therapy. Conclusion HIV-associated atherosclerosis presents a considerable health burden, characterized by distinctive non-calcified and inflammatory plaques vulnerable to rupture. Thrombus aspiration during PCI emerged as a valuable strategy, reducing thrombotic burden and contributing to improved clinical outcomes in people living with HIV.

Proteomics in low CVD risk black women living with HIV: H-ART to Heart Study

Abstract Background 39 million people worldwide are living with HIV (human immunodeficiency virus), acquired immune deficiency syndrome (AIDS)-related deaths have reduced by 51% since the peak in 2004. BWLWH represent 42% of those infected but only 9% are represented in clinical trials. HIV/AIDS has been shown to be associated with the development of heart failure, pulmonary hypertension and myocarditis. Previous studies in asymptomatic PLWH have revealed a high burden of underlying CVD and subclinical disease. The H-ART to Heart study is designed to examine potential signals and pathways of cardiovascular disease (CVD) in asymptomatic BWLWH with no traditional CV risk factors compared to HIV negative controls (-). Methods A cross-sectional study comparing asymptomatic BWLWH aged 35-55yrs (diagnosed >10 yrs, with undetectable viral loads) to HIV negative controls. Black African/Caribbean women without known CV risk factors (hypertension, hyperlipidaemia, diabetes, smoking, inflammatory arthritis, depression, severe mental illness) or hepatitis co-infection were included. Assessment included blood pressure (BP), 10yr CVD risk calculation % (Q-Risk 3), bloods including lipids. A targeted discovery proteomics approach was used to evaluate 92 unique proteins using the O-link Target 96 Cardiovascular II panel. Results 48 participants were recruited (23 BWLWH; 25 controls), mean duration of HIV was 17.6 years, mean duration of ART was 11.5 years, demographic details - Age 47.7± 44.7±; p=0.06, BP 125/77 v 123/79 ; p=0.89; BMI (kg/m²) 30.1±5.1 v 28.51±4.27 p=0.25; cLDL 3.49±1.22 v 2.42±0.74 p<0.02; Total Chol:HDL ratio 3.01±0.98 v 2.77±0.56 p=0.353; Q-Risk 3 1.92%±1.27 v 1.49%±1.12 p=0.219; There were no significant differences in baseline data apart from higher mean cLDL in BWLWH. Of the 92 proteins tested, 9 were significant in BWLWH (Figure 1). As demonstrated by the Heat map. Conclusion Data from our study of asymptomatic low risk BWLWH with no CVD risk factors indicates several pathways (Figure 2.) for further investigation in this previously under investigated vulnerable patient sub group. Whether this finding is of importance in CV risk assessment of BWLWH remains to be seen.

Concept Analysis of Psychosocial Distress Among African American and Latine Men Who Have Sex With Men: Implications for HIV Care.

The aim of this study is to provide conceptual clarity on psychosocial distress among African American and Latine men who have sex with men living with human immunodeficiency virus. Concept analysis. The 8-step Walker and Avant framework guided the concept analysis of psychosocial distress tailored to this patient population. A literature review was conducted using the research databases PubMed/Medline, PsycINFO, the Cumulated Index of Nursing and Allied Health Literature and Scopus with the selected search terms. A total of 7 articles were retrieved and analysed to explicate the antecedents, attributes, and consequences of psychosocial distress in this population. Four cases were developed to further clarify the concept of psychosocial distress; a model case, borderline case, related case and contrary case. As experienced by African American and Latine men who have sex with men living with human immunodeficiency virus, psychosocial distress is defined as a state of suffering due to uncontrollable structural and/or social factors that threaten the individual's existence and/or livelihood based on their social identity as a racial/ethnic, sexual minority. The concept analysis of psychosocial distress can be useful to guide future theory and measurement development to enhance disease-specific and general health outcomes for sexual and racial/ethnic minoritised men who have sex with men. Not applicable. No patient or public contribution.

Aerobic exercise capacity improvement of patients with human immunodeficiency virus one year post-treatment initiation by integrase inhibitors

Abstract Background Infection by Human Immunodeficiency Virus (HIV) leads to chronic inflammation and subsequently to the early development of cardiovascular (CV) disease in young adults. Initiation of antiretroviral therapy (ART) usually leads to patient’s body weight and blood pressure increase. Cardiopulmonary exercise test (CPET) evaluates aerobic exercise capacity and subsequently cardiovascular and respiratory function. Aim of this study is the investigation of any treatment-induced changes in aerobic exercise capacity in treatment naïve young HIV patients’ at 1-year post HIV treatment initiation by different ART agents. Methods We studied 46 recently diagnosed and treatment naïve young HIV patients (37+10 years, 87% males, 62% smokers) at baseline and 1-year post ART initiation (integrase or protease inhibitors). Twenty-six (26) patients were randomly treated by the newer integrase inhibitor Dolutegravir (Group A, mean age=36+9 years, 100% males, 77% smokers) while 19 patients by the older protease inhibitor Darunavir/Cobicistat (Group B, mean age=37+10 years, 90% males, 47% smokers). All patients were submitted in CPET at baseline and 1-year post ART initiation. We estimated any changes in body mass index (BMI), systolic blood pressure (SBP) and CPET parameters (peak VO2, Oxygen pulse, WorkLoad, VE/VCO2) at 1-year post ART initiation. Results At baseline and 1-year re-evaluation, we found no differences between groups regarding age, BMI and CPET parameters. In the whole HIV population, we found an increase in body weight (76+12 vs. 82+15kg, p<0.001), SΒΡ (124+12 vs. 132+14mmHg, p<0.001), WorkLoad (176+35 vs. 186+35watt, p<0.001) and peak VO2 (2171+437 vs. 2299+491ml/min, p=0.03) at 1-year re-evaluation. In Group A, body weight (p<0.001), SBP (p=0.07), WorkLoad (p=0.006) and peak VO2 (p=0.01) were increased while in Group B, body weight (p<0.001), SBP (p=0.001) και WorkLoad (p=0.01) were also increased. Conclusions Aerobic exercise capacity is improved 1-year post-treatment initiation by the newer integrase inhibitor Dolutegravir in treatment-naïve HIV patients despite the adverse BMI and SBP increase. The newer Dolutegravir probably exhibits a more favorable CV profile in HIV patients compared to the older Darunavir/Cobicistat.Re-evaluation 1-year post ART initiation

Effect of interleukin 1b inhibition with canakinumab on inflammation and viral persistence in people with human immunodeficiency virus

Abstract Introduction Effectively treated people with HIV (PWH) have elevated risk of cardiovascular disease (CVD). Inflammatory markers are predictive of CVD and mortality among PWH. The role of the myeloid system in driving inflammation and atherosclerosis has been recently recognized. Canakinumab (a monoclonal antibody to IL-1β) reduces inflammation and CVD events among people with elevated hsCRP after myocardial infarction without HIV. We evaluated the impact of IL-1β inhibition using canakinumab on HIV parameters, inflammation, HIV persistence markers, arterial inflammation, and hematopoietic activity in PWH. Methods PWH on effective ART who had CVD or were at risk for CVD were randomized 2:1 to receive 150 mg of canakinumab subcutaneously or matched placebo at weeks 0 and 12. Arterial inflammation and bone marrow metabolic activity were assessed using F18 FDG PET/CT at baseline and week 18. T cell and monocyte activation were evaluated using multiparameter spectral cytometry. The viral reservoir was quantified using Tat/rev Induced Limiting Dilution Assay (TILDA), HIV DNA and cell-associated RNA. The primary endpoints were change in CD4 and CD8 count. We assessed group effects over time using linear mixed effects models. Results 33 individuals were randomized (median age of 60 years old (IQR 57.5, 64.5) and 94% male); 25 received canakinumab and 8 received placebo. There were no significant differences at baseline. As expected, IL-1β increased among those treated with canakinumab at weeks 4- 24 (p<0.01 for each) and returned to baseline at week 36. There was one death from sepsis in an individual aged 84 with CVD and poorly controlled diabetes who received canakinumab. There were no significant changes in CD4 count, CD8 count, platelet count, creatinine, AST, or ALT by group. Treatment was not associated with a greater reduction in arterial inflammation in the most diseased segment compared to placebo (-6.9%; 95% CI -30.4 to 24.5%; p=0.62). However, bone marrow metabolic activity decreased in the canakinumab group versus placebo (-14.4%, 95% CI -26.5% to -0.2%; p=0.047). Treatment was associated with increased CD163 expression on monocytes at weeks 24 (p=0.03) and 36 (p<0.001), and lower caspase activity at week 36 (p=0.02). There was expansion of anti-inflammatory CD16+ patrolling monocytes that co-express CD163+CX3CR1+ and a decrease in pro-inflammatory CD16+ patrolling monocytes that are Caspase1+CCR2+. Treatment was not associated with differences in hsCRP, IL-6, IL-16, IL-18, MCP-1, sCD14, sCD163, T cell subsets, NK cell subsets, or viral persistence markers. Conclusion Among treated PWH, targeted inhibition of IL-1β using canakinumab results in decreased bone marrow metabolic activity and a shift toward anti-inflammatory monocyte populations. These findings shed light on mechanisms underlying how targeted IL-1β inhibition using canakinumab prevents CVD events by altering monocyte populations and reducing systemic inflammation.

The impacts of tobacco and nicotine on HIV-1 infection, inflammation, and the blood-brain barrier in the central nervous system

Human immunodeficiency virus (HIV-1) remains a persistent global health crisis. Even while successfully virologically suppressed, people with HIV (PWH) experience a higher risk for inflammatory disorders such as HIV-associated neurocognitive disorder (HAND). Tobacco use puts PWH at higher risk for neurocognitive symptoms resulting from HIV-associated neuroinflammation. The NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome has been implicated as a driver of HIV-associated inflammation, including HAND. Nicotine, the psychoactive component of tobacco smoke, has also been shown to signal through the NLRP3 inflammasome and modulate inflammatory signaling in the CNS. Here, we explore the impacts of nicotine and tobacco on the complex neurobiology of HAND, including effects on cognition, inflammation, viral latency, and blood-brain barrier integrity. We outline nicotine’s role in the establishment of active and latent infection in the brain and posit the NLRP3 inflammasome as a common pathway by which HIV-1 and nicotine promote neuroinflammation in PWH.

Blood microbiota in HIV-infected and HIV-uninfected patients with suspected sepsis detected by metagenomic next-generation sequencing

BackgroundInformation on the comparison of blood microbiota between human immunodeficiency virus (HIV)-infected and HIV-uninfected patients with suspected sepsis by metagenomic next-generation sequencing (mNGS) is limited.MethodsRetrospectively analysis was conducted in HIV-infected and HIV-uninfected patients with suspected sepsis at Changsha First Hospital (China) from March 2019 to August 2022. Patients who underwent blood mNGS testing were enrolled. The blood microbiota detected by mNGS were analyzed.ResultsA total of 233 patients with suspected sepsis who performed blood mNGS were recruited in this study, including 79 HIV-infected and 154 HIV-uninfected patients. Compared with HIV-uninfected patients, the proportions of mycobacterium (p = 0.001), fungus (p < 0.001) and viruses (p < 0.001) were significantly higher, while the proportion of bacteria (p = 0.001) was significantly lower in HIV-infected patients. The higher positive rates of non-tuberculous mycobacteriosis (NTM, p = 0.022), Pneumocystis jirovecii (P. jirovecii) (p = 0.014), Talaromyces marneffei (T. marneffei) (p < 0.001) and cytomegalovirus (CMV) (p < 0.001) were observed in HIV-infected patients, compared with HIV-uninfected patients. In addition, compared with HIV-uninfected patients, the constituent ratio of T. marneffei (p < 0.001) in the fungus spectrum were significantly higher, while the constituent ratios of Candida (p < 0.001) and Aspergillus (p = 0.001) were significantly lower in HIV-infected patients.ConclusionsSignificant differences in the blood microbiota profiles exist between HIV-infected and HIV-uninfected patients with suspected sepsis.

Bartonella endocarditis: lessons learnt from an African cohort

Abstract Background Bartonella (B) quintana endocarditis is a preventable, vector-borne, and important cause of blood culture-negative endocarditis (BCNE). The ESC guideline for the management of endocarditis recommends blood serology (IgG titer ≥800) and polymerase chain reaction (PCR) testing on both blood and valvular tissue for diagnosis. Access to these molecular technologies is limited in Africa and there is a paucity of B. quintana endocarditis research on the continent. Purpose Record the clinical picture and explore the risk factors for disease and the diagnostic utility of immunofluorescence (IFA) in PCR-proven cases with B. quintana endocarditis. Methods Data were analysed from a prospective observational cohort study of patients with infective endocarditis managed at our institution. All BCNE cases from October 2019 to January 2024 were evaluated to identify patients with PCR-proven B. quintana on valvular tissue. A commercially available IFA was used for blood serology testing. 16S rRNA PCR testing with sequencing was performed on valvular tissue. Results Thirty five of the 58 cases (60.3%) with BCNE were diagnosed with Bartonella endocarditis. A diagnosis of PCR-proven B. quintana endocarditis was made in 21 cases. Of these, seven patients (33.3%) were either homeless or lived in informal housing. Thirteen patients (61.9%) had an alcohol-use disorder. Four patients (19%) were Human Immunodeficiency (HIV) virus- positive. Eighteen patients (85.7%) reported the onset of symptoms more than two weeks before presentation. Common presenting symptoms were dyspnea (n=21;100%), loss of weight (n=10;47.6%) and fever (n=7;33.3%). Common clinical features were digital clubbing (n=17;80.9%), pallor (n=13; 61.9%), microscopic haematuria (n=12; 57.1%) and severe regurgitant lesions (n=21; 100%). Blood serology was available in 17 patients with an IgG titer (1≥256) in all patients apart from one (1:64). Only one case (5.8%) had an IgG titre ≥800. The most common isolated valve lesion on echocardiography was severe aortic regurgitation (n=10;47.6%). Surgical replacement and repair were performed in 17(80.9%) and 4(19%) patients respectively. The one-, three- and six-month mortality was 14%, 14 % and 14% respectively. No cases of relapse were reported. Discussion B.quintana is the most prevalent cause of BCNE in our centre. The typical clinical and echocardiographic profile was consistent with the reported literature of a destructive endocarditis in a patient with a low socioeconomic background. Despite this, the surgical outcome is fair and comparable to European data. The IFA used in this study is different to the assay referenced in the ESC guideline and may explain the relatively low serology titres observed (despite PCR-proven disease). Further study with the commercial IFA is needed to determine a cut-off titre that will give a comparable sensitivity to the referenced in-house IFA.Destructive aortic valve endocarditisResultant severe aortic regurgitation

Real-world evidence on pulmonary arterial hypertension: interim analysis from the Italian observational study INSPECTIO

Abstract Background Pulmonary arterial hypertension (PAH) is a rare, progressive disease leading to right-sided heart failure. The interest in risk assessment based on non-invasive parameters is growing, and insights from clinical practice are needed in this regard. INSPECTIO is an Italian observational study aimed at filling this knowledge gap. The results of an interim analysis at month 12 are presented below. Purpose The primary objective was to assess the change from baseline to month 12 in the number of the non-invasive low-risk parameters among World Health Organization functional class, 6-minutes walking distance, Brain Natriuretic Peptide (BNP) or N-terminal proBNP. Secondary objectives are the evaluation of echocardiographic and haemodynamic parameters, and the proportion of patients in which the therapy was optimized according to the guidelines. Methods Prospective, multicentre study on PAH patients at low/intermediate mortality risk treated with macitentan and/or selexipag as part of the oral combination therapy. Results Among 177 patients who were enrolled in 29 centres, 148 patients [median age 63.0 years (Q1/Q3: 53.5/73.0), 76.4% females] completed the 12-month follow up and were considered for this analysis. The median time from PAH diagnosis was 22.6 months (4.9/60.1). Sixty-four (43.2%) patients had idiopathic PAH; 4 (2.7%) heritable; 80 (54.1%) associated with other diseases [58 (72.5%) connective tissue disease, 11 (13.8%) congenital heart disease corrected for at least one year, 5 (6.3%) portal hypertension, 5 (6.3%) human immunodeficiency virus infection, 1 (1.3%) drug and toxins]. At baseline, 45.9% patients and 28.4% were in double and triple oral combination therapy, respectively. Primary objective: at month 12, the number of noninvasive low-risk parameters increased in 43 (29.1%) patients and remained stable in 80 (54.1%) patients [mean change 0.16 (p=0.017)]. The values at baseline, at month 12 and the change from baseline for each noninvasive parameter are shown in Table 1. Mean right atrial (RA) area (end-systole) and tricuspid annular plane systolic excursion (TAPSE) remained unchanged while a reduction of systolic pulmonary artery pressure (sPAP) was observed. Regarding the haemodynamic parameters, the mean pulmonary arterial pressure decreased [median change -4.5, (p=0.0346)], while cardiac index, pulmonary vascular resistance, and RA pressure remained stable (Table 2). The number of patients on triple therapy increased from 42 to 51 (+21.4%). Conclusions This study confirms that a noninvasive low-risk profile can be achieved with current combination PAH therapy. The modest or absent changes in echocardiographic and hemodynamic parameters suggest that treatment of PAH in real world is yet to be improved; on the other hand, the optimization of therapy in a significant portion of patients can possibly account for the improvement or stabilization observed.Noninvasive parametersEcho and hemodynamic parameters

O ENGAJAMENTO DOS ESTUDANTES DE MEDICINA COM AS PRÁTICAS PROFILÁTICAS DO HIV

The human immunodeficiency virus (HIV) remains one of the main global public health challenges, with approximately 1.5 million new infections in 2021, despite the therapeutic advances that have transformed the prognosis of AIDS. In Brazil, HIV has an incidence rate of 17.69 cases per 100,000 inhabitants in 2020, with a significant increase among young people aged 13 to 29, especially in the North and Northeast regions. This cross-sectional study analyzed 50 medical students from a university in Brazil, investigating the association between age group and safe sex practices, such as the use of condoms, as well as the perception of vulnerability to HIV. The results indicate that 61.2% of the students used condoms during sexual relations in the last 12 months, with no significant correlation with age group (p=0.507). However, 50% of the students justified not using condoms because they trusted their partner, and 82% believed that they would be unlikely to be infected with HIV because of their social environment. Statistical analysis also showed that the perception of invulnerability to HIV does not vary significantly with age group (p=0.350). This study investigated risk perception and condom use among medical students, concluding that there is no significant correlation between age group and safe practices. Trust in the partner was a relevant factor in the non-use of condoms, highlighting the need for educational campaigns to promote preventive behaviors and awareness among future health professionals.

Dual Antimicrobial Activity of HTCC and Its Nanoparticles: A Synergistic Approach for Antibacterial and Antiviral Applications Through Combined In Silico and In Vitro Studies

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC), a quaternized chitosan derivative, has been shown to exhibit a broad spectrum of antimicrobial activity, especially against bacteria and enveloped viruses. Despite this, molecular docking studies showing its atomic-level mechanisms against these microorganisms are scarce. Here, for the first time, we employed molecular docking analyses to investigate the potential antibacterial activity of HTCC against Staphylococcus aureus and its antiviral activity against human immunodeficiency virus 1 (HIV-1). According to the findings, HTCC exhibited promising antibacterial activity with high binding affinities; however, it had limited antiviral activity. To validate these theoretical outcomes, experimental studies were conducted. Different derivatives of HTCC were synthesized and characterized using NMR, XRD, FTIR, and DLS. The in vitro assays validated the potent antibacterial efficacy of HTCC against S. aureus, whereas the antiviral studies did not show good antiviral activity. However, our research also revealed a promising avenue for further exploration of the antimicrobial activity of HTCC nanoparticles (NPs), since, thus far, no studies have been conducted to show the antiviral activity of HTCC NPs against HIV-1. The nanosized HTCC exhibited superior antiviral performance compared to the parent polymers, with complete (100%) inhibition of HIV-1 viral activity at the highest tested concentration (0.33 mg/mL).

Pulmonary arterial hypertension in human immunodeficiency virus infections

Pulmonary arterial hypertension (PAH) is an important health issue in the twenty-first century. The introduction of highly active retroviral therapy has prolonged survival in patients infected with the human immunodeficiency virus (HIV), and this has led to the emergence of new health issues, including PAH, in those patients. This review considers the advances in understanding the pathophysiology of PAH in HIV infections and the approaches to the treatment of these patients. Keywords: Pulmonary arterial hypertension, HIV, pathophysiology, treatment

Tumor Initiation and Progression in People Living on Antiretroviral Therapies

Antiretroviral therapy (ART) has significantly extended the lifespan of people living with Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS), thereby transforming the disease into a manageable chronic condition. However, this increased longevity has led to a higher incidence of non-AIDS-defining cancers (NADCs) among this population. In this holistic review, we explore the complex interactions between HIV, ART, and cancer development, focusing on how ART influences tumor initiation and progression in people living with HIV/AIDS (PLWHA). Our findings from this reveal several critical aspects of cancer risk in PLWHA. Firstly, while ART restores immune function, it does not fully normalize it. Chronic immune activation and persistent inflammation continue to be prevalent, creating a conducive environment for oncogenesis. Additionally, PLWHA are more susceptible to persistent infections with oncogenic viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV), further increasing cancer risk. Some ART drugs have been implicated in genotoxicity and mitochondrial dysfunction, potentially promoting tumorigenesis. ART-induced metabolic changes, including insulin resistance and dyslipidemia, are also associated with heightened cancer risk. Common NADCs in PLWHA include lung cancer, liver cancer, anal cancer, and Hodgkin lymphoma, each with distinct etiologies linked to both HIV-related and ART-related factors. The interplay between HIV infection, chronic inflammation, immune restoration via ART, and the direct effects of ART drugs creates a unique cancer risk profile in PLWHA. Although ART reduces the incidence of AIDS-defining cancers, it does not confer the same protective effect against NADCs. Persistent HIV-related inflammation and immune activation, despite viral suppression, are key factors in cancer development. Additionally, long-term exposure to ART may introduce new oncogenic risks. These insights highlight the need for integrated cancer screening and prevention strategies tailored to PLWHA. Future research is needed to focus on identifying biomarkers for early cancer detection and developing ART regimens with lower oncogenic potential. Healthcare providers should be vigilant in monitoring PLWHA for cancer and adopt comprehensive screening protocols to mitigate the increased cancer risk associated with ART.

Real-world clinical features and survival outcomes in diffuse large B-cell lymphoma patients with hepatitis B virus infection

ObjectiveHepatitis B virus (HBV) infection is associated with the incidence and prognosis of diffuse large B-cell lymphoma (DLBCL), and previous studies differ in terms of clinical characteristics and prognostic factors. In this study, we explored the clinical features and prognostic characteristics of real-world DLBCL patients infected with HBV.MethodsPatients with pathologically diagnosed primary DLBCL at West China Hospital of Sichuan University were enrolled. Patients with follicular lymphoma-transformed DLBCL, primary central nervous system DLBCL, and hepatitis C virus, hepatitis E virus, human immunodeficiency virus, or syphilis infections were excluded. Ultimately, a total of 941 patients were included in this study. All patients included in the study underwent HBV serum marker testing before treatment. The demographic features, clinical characteristics and treatments of patients with different HBV infection states were collected and analyzed comprehensively to identify prognostic factors for OS and PFS.ResultsStatistical analysis of the data revealed that hepatitis B surface antigen positive (HBsAg +) DLBCL patients were younger and more likely to present with advanced disease, germinal center B cell-like subtype, B symptoms and splenic involvement. There were no significant differences in OS or PFS among patients with different HBV infection statuses (χ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upchi$$\\end{document}2 = 0.139, P = 0.933; χ2 = 0.787, P = 0.675); R-CHOP/R-CHOP-like regimens improved prognosis in HBsAg + DLBCL patients (OS: χ2 = 7.679, P = 0.006; PFS: χ2 = 9.042, P = 0.003); antiviral prophylaxis for HBsAg + DLBCL patients improved OS and PFS (HR: 0.336, P = 0.012, 95% CI [0.143, 0.788]; HR: 0.397, P = 0.032, 95% CI [0.171, 0.925]), with tenofovir treatment being particularly effective (χ2 = 4.644, P = 0.031; χ2 = 4.554, P = 0.033).ConclusionsHBsAg + DLBCL patients have unique clinical characteristics, and the use of CD20 monoclonal antibody based regimens significantly improves the outcome and prognosis of patients with HBsAg + DLBCL. Anti-HBV therapy, especially tenofovir, improves the prognosis of DLBCL patients with HBV presenting infection. Timely and sustained antiviral prophylaxis should be the standard strategy for treating DLBCL patients with HBV infection to optimize the efficacy of chemotherapy and immunotherapy.