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This study examined low bone mineral density (BMD) prevalence and associated factors among Chinese people living with HIV (PLWH), uncovering a persistent high BMD risk in older individuals, even after adjusting for age and body mass index (BMI). Notably, lopinavir/ritonavir (LPV/r) therapy was linked to reduced BMD, highlighting the imperative need for regular BMD monitoring and interventions in older PLWH. PURPOSE: HIV infection and antiretroviral therapy (ART) have been shown to contribute to lower BMD, resulting in an increased susceptibility to osteopenia and osteoporosis. However, there is limited knowledge about the prevalence of reduced BMD and its associated factors among Chinese PLWH. In this cross-sectional study, we aimed to investigate the prevalence and factors associated with low BMD among PLWH in China. METHODS: We retrospectively enrolled PLWH and non-HIV volunteers who underwent dual-energy X-ray absorptiometry (DXA) scans to measure bone density. Demographic information, laboratory test results, ART regimens, and treatment duration were collected. Univariate and multiple regression analyses were performed to identify factors influencing abnormal bone mass in PLWH. RESULTS: A total of 829 individuals were included in this study, comprising the HIV group (n = 706) and the non-HIV group (n = 123). The prevalence of low BMD among all PLWH was found to be 13.88% (98 out of 706). However, among PLWH aged 50 years and above, the prevalence increased to 65.32% (81 out of 124). In contrast, control subjects in the same age group had a prevalence of 38.21% (47 out of 123). After adjusting for age and BMI, older PLWH still demonstrated a higher prevalence of low BMD compared to the non-HIV group (68.24% vs 34.94%, P < 0.001). Multivariate analysis revealed that older age was strongly associated with a higher risk of low BMD among PLWH, with an odds ratio (OR) of 6.28 for every 10-year increase in age in the ART-naïve population (95% confidence intervals [CIs], 3.12-12.65; P < 0.001) and OR of 4.83 in the ART-experienced population (3.20-7.29, P < 0.001). Within the ART-experienced group, current LPV/r treatment was associated with an increased risk of low BMD (OR = 3.55, 1.24-10.14, P < 0.05), along with lower BMI (OR = 0.84, 0.75-0.95, P < 0.05), and elevated alkaline phosphatase (OR = 1.02, 1.01-1.03, P < 0.01). CONCLUSION: The prevalence of low BMD is higher among PLWH aged 50 years and above compared to non-HIV individuals. The use of LPV/r for ART is associated with reduced BMD. These findings emphasize the importance of regular monitoring of BMD in older PLWH and the need for appropriate interventions to mitigate the risks of osteopenia and osteoporosis in this population.
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Absorciometría de Fotón , Densidad Ósea , Infecciones por VIH , Osteoporosis , Humanos , Estudios Transversales , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Prevalencia , Adulto , China/epidemiología , Estudios Retrospectivos , Osteoporosis/epidemiología , Factores de Riesgo , Anciano , Enfermedades Óseas Metabólicas/epidemiologíaRESUMEN
BACKGROUND: The global mortality rate resulting from HIV-associated cryptococcal disease is remarkably elevated, particularly in severe cases with dissemination to the lungs and central nervous system (CNS). Regrettably, there is a dearth of predictive analysis regarding long-term survival, and few studies have conducted longitudinal follow-up assessments for comparing anti-HIV and antifungal treatments. METHODS: A cohort of 83 patients with HIV-related disseminated cryptococcosis involving the lung and CNS was studied for 3 years to examine survival. Comparative analysis of clinical and immunological parameters was performed between deceased and surviving individuals. Subsequently, multivariate Cox regression models were utilized to validate mortality predictions at 12, 24, and 36 months. RESULTS: Observed plasma cytokine levels before treatment were significantly lower for IL-1RA (p < 0.001) and MCP-1 (p < 0.05) when in the survivor group. Incorporating plasma levels of IL-1RA, IL-6, and high-risk CURB-65 score demonstrated the highest area under curve (AUC) value (0.96) for predicting 1-year mortality. For 1-, 2- and 3-year predictions, the single-factor model with IL-1RA demonstrated superior performance compared to all multiple-variate models (AUC = 0.95/0.78/0.78). CONCLUSIONS: IL-1RA is a biomarker for predicting 3-year survival. Further investigations to explore the pathogenetic role of IL-1RA in HIV-associated disseminated cryptococcosis and as a potential therapeutic target are warranted.
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Tuberculosis is one of the most common opportunistic infections and a prominent cause of death in patients with human immunodeficiency virus (HIV) infection, in spite of near-universal access to antiretroviral therapy (ART) and tuberculosis preventive therapy. For patients with active tuberculosis but not yet receiving ART, starting ART after anti-tuberculosis treatment can complicate clinical management due to drug toxicities, drug-drug interactions and immune reconstitution inflammatory syndrome (IRIS) events. The timing of ART initiation has a crucial impact on treatment outcomes, especially for patients with tuberculous meningitis. The principles of ART in patients with HIV-associated tuberculosis are specific and relatively complex in comparison to patients with other opportunistic infections or cancers. In this review, we summarize the current progress in the timing of ART initiation, ART regimens, drug-drug interactions between anti-tuberculosis and antiretroviral agents, and IRIS.
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Antituberculosos , Interacciones Farmacológicas , Infecciones por VIH , Síndrome Inflamatorio de Reconstitución Inmune , Tuberculosis , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Tuberculosis/tratamiento farmacológico , Tuberculosis/complicaciones , Antituberculosos/uso terapéutico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Antirretrovirales/uso terapéutico , Antirretrovirales/efectos adversos , Terapia Antirretroviral Altamente Activa , Resultado del TratamientoRESUMEN
Trends in and risk factors for drug resistance in Mycobacterium tuberculosis (M. tuberculosis) in human immunodeficiency virus (HIV)-infected patients with active tuberculosis were analyzed. The clinical data of M. tuberculosis and HIV-coinfected patients treated at the Shanghai Public Health Clinical Center between 2010 and 2022 were collected. The diagnosis of tuberculosis was confirmed by solid or liquid culture. The phenotypic drug susceptibility test was carried out via the proportional method, and the resistance to first-line and second-line drugs was analyzed. Logistic regression analysis was performed to identify associated risk factors for drug resistance in M. tuberculosis. Of the 304 patients with a M. tuberculosis-positive culture and first-line drug susceptibility test results, 114 (37.5%) were resistant to at least one first-line anti-tuberculosis drug. Of the 93 patients with first-line and second-line drug susceptibility test results, 40 (43%) were resistant to at least one anti-tuberculosis drug, and 20 (21.5%), 27 (29.0%), 19 (20.4%), 16 (17.2%), and 14 (15.1%) were resistant to rifampicin, streptomycin, ofloxacin, levofloxacin, and moxifloxacin, respectively; 17 patients (18.3%) had multidrug-resistant tuberculosis (MDR-TB). Between 2010 and 2021, the rate of resistance to streptomycin and rifampicin ranged from 14.3% to 40.0% and from 8.0% to 26.3%, respectively, showing an increasing trend year by year. From 2016 to 2021, the rate of resistance to quinolones fluctuated between 7.7% and 27.8%, exhibiting an overall upward trend. Logistic regression analysis showed that being aged <60 years old was a risk factor for streptomycin resistance, mono-drug resistance, and any-drug resistance (RR 4.139, p = 0.023; RR 7.734, p = 0.047; RR 3.733, p = 0.009). Retreatment tuberculosis was a risk factor for resistance to rifampicin, ofloxacin, of levofloxacin (RR 2.984, p = 0.047; RR 4.517, p = 0.038; RR 6.277, p = 0.014). The drug resistance rates of M. tuberculosis to rifampicin and to quinolones in HIV/AIDS patients were high and have been increasing year by year. Age and a history of previous anti-tuberculosis treatment were the main factors associated with the development of drug resistance in HIV/AIDS patients with tuberculosis.
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Antituberculosos , Infecciones por VIH , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Mycobacterium tuberculosis/efectos de los fármacos , Factores de Riesgo , Femenino , Masculino , Infecciones por VIH/complicaciones , Infecciones por VIH/microbiología , Infecciones por VIH/tratamiento farmacológico , Adulto , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Persona de Mediana Edad , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , China/epidemiología , Coinfección/microbiología , Coinfección/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple , Adulto Joven , Farmacorresistencia Bacteriana , AncianoRESUMEN
Accumulating evidence show a potential association between tuberculosis and COVID-19 disease severity. To further clarify the impact of tuberculosis on COVID-19 disease severity and viral shedding duration, a retrospective study was conducted on 223 COVID-19 patients, including 34 with tuberculosis and 189 without tuberculosis. Clinical information and viral load shedding time were collected. A higher percentage of severe/critical COVID-19 diagnosis and deaths was observed in patients with tuberculosis than in those without tuberculosis (8.8% vs. 3.2%, p = 0.142; 2.9% vs. 1.1%, p = 0.393), and COVID-19 patients with tuberculosis had longer viral shedding than those without tuberculosis (median: 15.0 days vs. 11.0 days; p = 0.0001). Having tuberculosis (HR = 2.21, 95% CI 1.37-3.00; p = 0.000), being of elderly age (HR = 1.02, 95% CI 1.01-1.03; p = 0.001) and being diagnosed with severe or critical COVID-19 (HR = 5.63, 95% CI 2.10-15.05; p = 0.001) were independent factors associated with prolonged virus time of SARS-CoV-2. COVID-19 patients with tuberculosis receiving anti-tuberculosis therapy time (ATT) for <2 months had a significantly longer virus shedding duration than those receiving ATT for ≥ 4 months (17.5 vs. 11.5 days, p = 0.012). Our results demonstrated that COVID-19 patients with tuberculosis tend to have more severe disease and a worse prognosis, and tuberculosis prolonged viral shedding, highlighting special attention and/or care required for COVID-19 patients with tuberculosis receiving ATT for <2 months.
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COVID-19 , Tuberculosis , Humanos , Anciano , SARS-CoV-2 , Esparcimiento de Virus , Estudios Retrospectivos , Prueba de COVID-19 , Tuberculosis/complicaciones , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Gravedad del Paciente , ARN ViralRESUMEN
BACKGROUND: HIV-1 drug resistance is a huge challenge in the era of ART. OBJECTIVES: To investigate the prevalence and characteristics of acquired HIV-1 drug resistance (ADR) in Shanghai, China. METHODS: An epidemiological study was performed among people living with human immunodeficiency virus (PLWH) receiving ART in Shanghai from January 2017 to December 2021. A total of 8669 PLWH were tested for drug resistance by genotypic resistance testing. Drug resistance mutations (DRMs) were identified using the Stanford University HIV Drug Resistance Database program. RESULTS: Ten HIV-1 subtypes/circulating recombinant forms (CRFs) were identified, mainly including CRF01_AE (46.8%), CRF07_BC (35.7%), B (6.4%), CRF55_01B (2.8%) and CRF08_BC (2.4%). The prevalence of ADR was 48% (389/811). Three NRTI-associated mutations (M184V/I/L, S68G/N/R and K65R/N) and four NNRTI-associated mutations (V179D/E/T/L, K103N/R/S/T, V106M/I/A and G190A/S/T/C/D/E/Q) were the most common DRMs. These DRMs caused high-level resistance to lamivudine, emtricitabine, efavirenz and nevirapine. The DRM profiles appeared to be significantly different among different subtypes. CONCLUSIONS: We revealed HIV-1 subtype characteristics and the DRM profile in Shanghai, which provide crucial guidance for clinical treatment and management of PLWH.
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Seropositividad para VIH , VIH-1 , Humanos , VIH-1/genética , Estudios Retrospectivos , China/epidemiología , AlquinosRESUMEN
BACKGROUND: Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial. METHODS: In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed. RESULTS: A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate. CONCLUSIONS: Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).
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COVID-19 , Inhibidores de Proteasa de Coronavirus , Adulto , Humanos , Administración Oral , Antivirales/administración & dosificación , Antivirales/efectos adversos , Antivirales/farmacología , Antivirales/uso terapéutico , China , Proteínas M de Coronavirus/antagonistas & inhibidores , Proteínas M de Coronavirus/metabolismo , Inhibidores de Proteasa de Coronavirus/administración & dosificación , Inhibidores de Proteasa de Coronavirus/efectos adversos , Inhibidores de Proteasa de Coronavirus/farmacología , Inhibidores de Proteasa de Coronavirus/uso terapéutico , COVID-19/metabolismo , COVID-19/terapia , Tratamiento Farmacológico de COVID-19/métodos , Método Doble Ciego , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , Ritonavir/farmacología , Ritonavir/uso terapéutico , SARS-CoV-2/efectos de los fármacos , Factores de Tiempo , Combinación de MedicamentosAsunto(s)
Infecciones por VIH , VIH-1 , Linfoma no Hodgkin , Humanos , Leucocitos Mononucleares , ADNRESUMEN
Background: The incidence of progressive multifocal leukoencephalopathy (PML) in people living with HIV (PLWH) is 2%-4%. Currently, there is no effective therapeutic strategy for the treatment of PML in PLWH, resulting in a mortality of up to 50%. This study aimed to identify risk factors of death and prognostic markers in people living with HIV with PML. Methods: A retrospective cohort study of AIDS-related PML individuals was conducted from January 1, 2015, to October 1, 2022, in Shanghai, China. PLWH who were diagnosed with PML for the first time were included. Kaplan-Meier curve and Cox regression were used to analyze the survival and its predictors. Levels of inflammatory markers and immune checkpoint inhibitors in blood and cerebrospinal fluid (CSF) were measured in the prestored samples using bead-based multiplex assay Indolamine 2,3-dioxygenase was determined using ELISA. Results: Twenty of 71 subjects had initiated antiretroviral therapy (ART) before PML onset and no patients discontinued ART during this period. In total, 34 patients (47.9%) had opportunistic infections (OIs), the median CD4+ T cell count was 73.0 (33.0-149.0) cells/µL. The estimated probability of survival at six months was 78% (95% confidential intervals [CIs]:0.63-0.85). OIs, low CD4+ T cell count were associated with lower estimated six-month survival (hazard ratio 8.01, 95% CIs: 1.80-35.00, P=0.006 and 5.01, 95% CIs:1.57-16.03, p=0.007). Indolamine 2,3-dioxygenase activity in CSF of non-survivors group were higher than survivors group (p<0.05). Conclusions: The survival rate of AIDS-related PML in the modern ART era was higher than the survival rate a decade ago. Low CD4+T cell count, OIs, were all associated with death of individuals with AIDS-related PML. The role of IDO in AIDS-related PML warrant further investigation.
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Síndrome de Inmunodeficiencia Adquirida , Dioxigenasas , Infecciones por VIH , Leucoencefalopatía Multifocal Progresiva , Humanos , Leucoencefalopatía Multifocal Progresiva/complicaciones , Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico , Leucoencefalopatía Multifocal Progresiva/epidemiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Estudios Retrospectivos , Pronóstico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , China/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológicoRESUMEN
The precise role of indoleamine 2,3-dioxygenase (IDO) in cardiovascular diseases (CVD) among people living with HIV (PLWH) is still under debate, despite recognized links. This study aimed to investigate the impact of elevated IDO activity on endothelial dysfunction in PLWH. A total of 38 PLWH, who had not previously received anti-retroviral therapy (ART), were enrolled in the study. These participants were monitored for 36 months following the initiation of ART. Measurements including plasma levels of IDO activity, markers of endothelial dysfunction, inflammatory factors, and lipids. In vitro, human aortic endothelial cells (HAEC) were exposed to interferon-γ, an IDO inhibitor, a kynurenine 3-hydroxylase (KMO) inhibitor, as well as different concentrations of kynurenine. Pre-ART, PLWH demonstrated notably elevated plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1(sVCAM-1), and IDO activity in comparison to healthy controls. Post-ART, both IDO activity and sICAM-1 levels experienced a significant decrease, with IDO activity reaching levels comparable to those observed in healthy controls. Furthermore, a positive correlation was observed between IDO activity and sICAM-1 (p = 0.0002), as well as sVCAM-1 (p < 0.0001) before ART. In vitro, the augmentation of kynurenine concentration in the medium and the induction of IDO expression in HAEC resulted in increased production of reactive oxygen species (ROS), with minimal impact on endothelial dysfunction. From these findings, it can be concluded that long-term ART has the potential to restore the heightened IDO activity observed in PLWH. The overexpression of IDO primarily influences the expression of ROS in HAEC.
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Enfermedades Cardiovasculares , Células Endoteliales , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa , Especies Reactivas de Oxígeno , QuinureninaRESUMEN
INTRODUCTION: Cryptococcal meningitis (CM) is a serious and fatal fungal infection that affects individuals infected with human immunodeficiency virus (HIV). Despite treatment, recurrence of symptoms is common and could lead to poor outcomes. Corticosteroids are not always useful in treating symptom recurrence following HIV/CM; thus, alternative therapy is needed. Thalidomide has been reported to be effective in treating symptom recurrence in several patients with HIV/CM. This retrospective study aimed to investigate the efficacy and safety of thalidomide in the treatment of symptom recurrence following HIV/CM. METHODS: Patients who were treated with thalidomide for symptom recurrence following HIV/CM were retrospectively included. Clinical outcomes and adverse events were recorded and analyzed. RESULTS: Sixteen patients admitted between July 2018 and September 2020 were included in the analysis. During a median follow-up period of 295 (166, 419) days, all patients achieved clinical improvement in a median of 7 (4, 20) days. Among them, nine (56%) achieved complete resolution of symptoms at a median of 187 (131, 253) days, including 40% (2/5) of immune reconstitution inflammatory syndrome (IRIS), 50% (3/6) of patients with elevated ICP only, and 80% (4/5) of patients with symptoms only. Seven (43%) patients experienced nine episodes of adverse events, but no severe adverse event attributable to thalidomide was observed. None of the patients withdrew from thalidomide due to adverse events. CONCLUSION: Thalidomide appears to be effective and safe in treating different types of symptom recurrence in HIV/CM. This study provides preliminary evidence supporting future randomized clinical trials to further investigate the efficacy and safety of thalidomide in treating symptom recurrence in this population.
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Coronavirus disease-2019 has impacted the world globally. Countries and health care organizations across the globe responded to this unprecedented public health crisis in a varied manner in terms of public health and social measures, vaccination development and rollout, the conduct of research, developments of therapeutics, sharing of information, and in how they continue to deal with the widespread aftermath. This article reviews the various elements of the global response to the pandemic, focusing on the lessons learned and strategies to consider during future pandemics.
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COVID-19 , Humanos , SARS-CoV-2 , Salud PúblicaRESUMEN
BACKGROUND: Men who have sex with men (MSM) is a key population for preventing HIV in China, yet pre-exposure prophylaxis (PrEP) is not widely accepted in this population. The objective of this manuscript was to assessed the barriers in the acknowledgement and uptake focusing the demand side. METHODS: An online questionnaire survey was conducted from December 2018 to January 2019. All participants were required to scan two-dimensional code which was the online crowdsourcing survey platform to complete the electronic questionnaire anonymously. RESULTS: Among 1915 MSM from thirty-four cities of China, 512 (26.7%) versus 1617 (84.4%) had an objective or subjective need of PrEP, respectively. One hundred and six (5.5%) reported affordability and only 23 (1.2%) had ever taken it. Age, living alone and occupation were associated with the objective needs. Age, income, sexual behavior were associated with actual usage. The participants who they had objective need to use PrEP are the population which we should focus on. CONCLUSION: A wide disconnect exists among the objective need, willingness, affordability and uptake of PrEP. Cost was the most prevalent barrier, accounting for 78.22% of individuals who needed and wished for PrEP but finally failed to receive it. The findings might facilitate optimizing future allocation of resources to better promote PrEP in Chinese MSM.
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Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Humanos , Masculino , China/epidemiología , Estudios Transversales , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Conducta Sexual , Promoción de la SaludRESUMEN
INTRODUCTION: This study aimed to evaluate the prevalence of HIV-1 mutation V179D/E and the effect of V179D/E on the virological response to first-line efavirenz-based regimens among antiretroviral treatment (ART)-naïve patients. METHODS: An ambispective cohort study was conducted. All ART-naïve patients who underwent baseline genotypic resistance testing between January 2019 and November 2021 were included in the analysis of the prevalence of the V179D/E mutation. Then, patients with identified V179D/E received the efavirenz-based regimen or the protease inhibitor (PI)/integrase strand transfer inhibitor (INSTI)-based regimen. The virological and immunological outcomes at week 48 were compared between the two groups. RESULTS: HIV-1 mutation V179D/E was identified in 252 out of 2568 ART-naïve patients, with a prevalence of 9.8% in Shanghai, China. A total of 206 participants were included in the efficacy analysis. Forty-six patients with altered ART regimens or incomplete follow-up data were excluded from the analysis. The baseline characteristics were comparable between the efavirenz group (n = 109) and the PI/INSTI group (n = 97). At week 48, a total of 96 participants (88.1%) in the efavirenz group and 92 participants (94.8%) in the PI/INSTI group had a viral load lower than 50 copies/mL (chi-square test, p = 0.086). In both groups, a lower proportion of participants achieved virological suppression among participants with a baseline viral load of at least 100,000 copies/mL compared with those with lower than 100,000 copies/mL (66.7% vs. 96.1% in the efavirenz group, p < 0.001; 87.1% vs. 98.4% in the PI/INSTI group, p = 0.039). The median increase from baseline in the CD4 count at week 48 was significantly greater in the PI/INSTI group (192 cells/µL) than in the efavirenz group (154 cells/µL) (p = 0.029). CONCLUSION: There is a high prevalence of V179D/E in ART-naïve patients with HIV-1 in Shanghai, China. The first-line efavirenz-based regimen may be not suitable for patients with HIV-1 mutation V179D/E, especially for those with a baseline viral load of at least 100,000 copies/mL. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2000034787).
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Background: Plasma level of polysaccharide (1 â 3)-ß-D-Glucan (ßDG), as a diagnostic marker of invasive fungal infection has been reported to be elevated in people living with HIV (PLWH). We assessed the association of circulating ßDG to inflammation and systemic immune activation and the effect of antiretroviral therapy (ART) on ßDG in PLWH. Method: Plasma and peripheral blood monocular cell samples from 120 PLWH naive to ART and after 1 year's ART were collected. Plasma levels of ßDG, markers of bacterial translocation, gut damage, and cellular immune activation were quantified. Result: The plasma ßDG levels were negatively correlated with CD4+ T cells count (r = -0.25, p = 0.005) and positively with HIV viral load (r = 0.28, p = 0.002) before ART. It was also positively correlated with immune activation markers, including PD-1 expression on CD4+ T cell (r = 0.40, p = 0.01) and CD8+ T cell (r = 0.47, p = 0.002), as well as HLADR+CD38+ co-expression on CD8+ T cell (r = 0.56, p = 0.0002), but not with the plasma levels of LPS (r = 0.02, p = 0.84), LPS binding protein (LBP, r = 0.11, p = 0.36), soluble LPS receptor sCD14 (r = 0.04, p = 0.68), intestinal fatty acid binding protein (IFABP, r = -0.12, p = 0.18), and regenerating islet-derived protein 3α (REG3α, r = 0.18, p = 0.06). After 1 year's ART, the levels of ßDG were significantly decreased compared to that in pre-ART (1.31 ± 0.24 Log10 pg/ml vs. 1.39 ± 0.18 Log10 pg/ml, p < 0.001). Conclusion: The level of plasma ßDG was associated with cellular immune activation and decreased after ART in PLWH, suggesting it could serve as a biomarker of immune activation and efficacy monitoring.
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Infecciones por VIH , beta-Glucanos , Biomarcadores , Proteínas de Unión a Ácidos Grasos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Receptores de Lipopolisacáridos , Lipopolisacáridos , Proteínas Asociadas a Pancreatitis , Receptor de Muerte Celular Programada 1RESUMEN
The prevalence of SARS-CoV-2 variants of concern (VOCs) is still escalating throughout the world. However, the level of neutralization of the inactivated viral vaccine recipients' sera and convalescent sera against all VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron) remains to be lack of comparative analysis. Therefore, we constructed pseudoviruses of five VOCs using a lentiviral-based system and analyzed their viral infectivity and neutralization resistance to convalescent and BBIBP-CorV vaccinee serum at different times. Our results show that, compared with the wild-type strain (WT), five VOC pseudoviruses showed higher infection, of which B.1.617.2 and B.1.1.529 variant pseudoviruses exhibited higher infection rates than wild-type or other VOC strains, respectively. Sera from 10 vaccinated individuals at the 1, 3 and 5-month post second dose or from 10 convalescent at 14 and 200 days after discharge retained neutralizing activity against all strains but exhibited decreased neutralization activity significantly against the five VOC variant pseudoviruses over time compared to WT. Notably, 100% (30/30) of the vaccinee serum samples showed more than a 2.5-fold reduction in neutralizing activity against B.1.1.529, and 90% (18/20) of the convalescent serum samples showed more than 2.5-fold reduction in neutralization against B.1.1.529. These findings demonstrate the reduced protection against the VOCs in vaccinated and convalescent individuals over time, indicating that it is necessary to have a booster shot and develop new vaccines capable of eliciting broad neutralization antibodies.