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1.
Virol J ; 18(1): 181, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488793

RESUMO

BACKGROUND: Transmitted drug resistance (TDR) that affects the effectiveness of the first-line antiretroviral therapy (ART) regimen is becoming prevalent worldwide. However, its prevalence and transmission among HIV-1 treatment-naïve patients in Guangdong, China are rarely reported. We aimed to comprehensively analyze the prevalence of TDR and the transmission clusters of HIV-1 infected persons before ART in Guangdong. METHODS: The HIV-1 treatment-naïve patients were recruited between January 2018 and December 2018. The HIV-1 pol region was amplified by reverse transcriptional PCR and sequenced by sanger sequencing. Genotypes, surveillance drug resistance mutations (SDRMs) and TDR were analyzed. Genetic transmission clusters among patients were identified by pairwise Tamura-Nei 93 genetic distance, with a threshold of 0.015. RESULTS: A total of 2368 (97.17%) HIV-1 pol sequences were successfully amplified and sequenced from the enrolled 2437 patients. CRF07_BC (35.90%, 850/2368), CRF01_AE (35.56%, 842/2368) and CRF55_01B (10.30%, 244/2368) were the main HIV-1 genotypes circulating in Guangdong. Twenty-one SDRMs were identified among fifty-two drug-resistant sequences. The overall prevalence of TDR was 2.20% (52/2368). Among the 2368 patients who underwent sequencing, 8 (0.34%) had TDR to protease inhibitors (PIs), 22 (0.93%) to nucleoside reverse transcriptase inhibitors (NRTIs), and 23 (0.97%) to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Two (0.08%) sequences showed dual-class resistance to both NRTIs and NNRTIs, and no sequences showed triple-class resistance. A total of 1066 (45.02%) sequences were segregated into 194 clusters, ranging from 2 to 414 sequences. In total, 15 (28.85%) of patients with TDR were included in 9 clusters; one cluster contained two TDR sequences with the K103N mutation was observed. CONCLUSIONS: There is high HIV-1 genetic heterogeneity among patients in Guangdong. Although the overall prevalence of TDR is low, it is still necessary to remain vigilant regarding some important SDRMs.

2.
Front Immunol ; 12: 724763, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489978

RESUMO

Characterizing the serologic features of asymptomatic SARS-CoV-2 infection is imperative to improve diagnostics and control of SARS-CoV-2 transmission. In this study, we evaluated the antibody profiles in 272 plasma samples collected from 59 COVID-19 patients, consisting of 18 asymptomatic patients, 33 mildly ill patients and 8 severely ill patients. We measured the IgG against five viral structural proteins, different isotypes of immunoglobulins against the Receptor Binding Domain (RBD) protein, and neutralizing antibodies. The results showed that the overall antibody response was lower in asymptomatic infections than in symptomatic infections throughout the disease course. In contrast to symptomatic patients, asymptomatic patients showed a dominant IgG-response towards the RBD protein, but not IgM and IgA. Neutralizing antibody titers had linear correlations with IgA/IgM/IgG levels against SARS-CoV-2-RBD, as well as with IgG levels against multiple SARS-CoV-2 structural proteins, especially with anti-RBD or anti-S2 IgG. In addition, the sensitivity of anti-S2-IgG is better in identifying asymptomatic infections at early time post infection compared to anti-RBD-IgG. These data suggest that asymptomatic infections elicit weaker antibody responses, and primarily induce IgG antibody responses rather than IgA or IgM antibody responses. Detection of IgG against the S2 protein could supplement nucleic acid testing to identify asymptomatic patients. This study provides an antibody detection scheme for asymptomatic infections, which may contribute to epidemic prevention and control.


Assuntos
Anticorpos Antivirais/sangue , Infecções Assintomáticas , Imunoglobulina G/sangue , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Proteínas Estruturais Virais/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/fisiologia , Sítios de Ligação de Anticorpos , Feminino , Humanos , Imunoglobulina G/classificação , Imunoglobulina M/imunologia , Cinética , Masculino , Pessoa de Meia-Idade , Testes de Neutralização/estatística & dados numéricos , SARS-CoV-2/química , Adulto Jovem
3.
Front Cell Infect Microbiol ; 11: 728415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34466405

RESUMO

Background: The second human pegivirus (HPgV-2) and hepatitis C virus (HCV) belong to the Flaviviridae family and share some common genome features. However, the two viruses exhibit significantly different genetic diversity. The comparison of intrahost dynamics of HPgV-2 and HCV that mainly reflect virus-host interactions is needed to elucidate their intrahost difference of genetic diversity and the possible mechanisms. Methods: Intrahost single nucleotide variations (iSNVs) were identified by means of next-generation sequencing from both cross-sectional and longitudinal samples from HPgV-2- and HCV-coinfected patients. The levels of human cytokines were quantified in the patient before and after HCV elimination by the treatment of direct-acting antivirals (DAA). Results: Unlike HCV, the viral sequences of HPgV-2 are highly conserved among HPgV-2-infected patients. However, iSNV analysis confirmed the intrahost variation or quasispecies of HPgV-2. Almost all iSNVs of HPgV-2 did not accumulate or transmit within host over time, which may explain the highly conserved HPgV-2 consensus sequence. Intrahost variation of HPgV-2 mainly causes nucleotide transition in particular at the 3rd codon position and synonymous substitutions, indicating purifying or negative selection posed by host immune system. Cytokine data further indicate that HPgV-2 infection alone may not efficiently stimulate innate immune responses since proinflammatory cytokine expression dramatically decreased with elimination of HCV. Conclusion: This study provided new insights into the intrahost genomic variations and evolutionary dynamics of HPgV-2 as well as the impact of host immune selection and virus polymerase on virus evolution. The different genetic diversity of HPgV-2 and HCV makes HPgV-2 a potential new model to investigate RNA virus diversity and the mechanism of viral polymerase in modulating virus replication.

4.
Arch Virol ; 166(10): 2853-2857, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34373969

RESUMO

Strains of the HIV-1 circulating recombinant forms (CRFs) 06_cpx and 56_cpx were identified for the first time in Guangzhou, China. The nearly full-length genome (NFLG) sequence was amplified, and the PCR products were sequenced by the Sanger method. The CRF06_cpx and CRF56_cpx strains were identified using the Basic Local Alignment Search Tool (BLAST) and confirmed by neighbour-joining (NJ) phylogenetic analysis. Additionally, these strains were found to contain transmitted drug resistance mutations that have little effect on first-line efavirenz (EFV)-based treatment. Genetic analysis of the detailed sequence data will provide more information on the HIV-1 epidemic in China.


Assuntos
Infecções por HIV/virologia , HIV-1/genética , Adulto , China/epidemiologia , Cidades/epidemiologia , Farmacorresistência Viral/genética , Feminino , Genoma Viral/genética , Genótipo , Infecções por HIV/epidemiologia , HIV-1/classificação , HIV-1/isolamento & purificação , Humanos , Masculino , Mutação , Filogenia , Recombinação Genética , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
5.
J Clin Invest ; 131(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34375315

RESUMO

BACKGROUNDChimeric antigen receptor (CAR) T cells have emerged as an approach to treat malignant tumors. This strategy has also been proposed for the treatment of HIV-1 infection. We have developed a broadly neutralizing antibody-derived (bNAb-derived) CAR T cell therapy that can exert specific cytotoxic activity against HIV-1-infected cells.METHODSWe conducted an open-label trial of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of bNAb-derived CAR T cell therapy in individuals infected with HIV-1 who were undergoing analytical interruption of antiretroviral therapy (ART).RESULTSA total of 14 participants completed only a single administration of bNAb-derived CAR T cells. CAR T cell therapy administration was safe and well tolerated. Six participants discontinued ART, and viremia rebound occurred in all of them, with a 5.3-week median time. Notably, the cell-associated viral RNA and intact proviruses decreased significantly after CAR T cell treatment. Analyses of HIV-1 variants before or after CAR T cell administration suggested that CAR T cells exerted pressure on rebound viruses, resulting in a selection of viruses with less diversity and mutations against CAR T cell-mediated cytotoxicity.CONCLUSIONNo safety concerns were identified with adoptive transfer of bNAb-derived CAR T cells. They reduced viral reservoir. All the rebounds were due to preexisting or emergence of viral escape mutations.TRIAL REGISTRATIONClinicalTrials.gov (NCT03240328).FUNDINGMinistry of Science and Technology of China, National Natural Science Foundation of China, and Department of Science and Technology of Guangdong Province.

6.
J Hazard Mater ; 420: 126668, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34329118

RESUMO

Surface Enhanced Raman Spectroscopy (SERS) could be a powerful technique for detecting trace gaseous sulfur-mustard, but it is still challenging due to the difficulty in efficiently capturing sulfur-mustard molecules by normal SERS substrates. Here, a chemically trapping strategy is presented for such detection via coating an ultrathin metal-oxide sensing layer on a SERS substrate. In the strategy, a SERS substrate Au-wrapped Si nanocone array is designed and fabricated by Si wafer-based organic template-etching and appropriate Au deposition, and coated with an ultrathin CuO for chemically capturing sulfur-mustard molecules. The validity of such strategy has been demonstrated via taking the gaseous 2-chloroethyl ethyl sulfide (a simulant of sulfur-mustard, or 2-CEES for short) as the target molecules. The response of the CuO-coated SERS substrate to the gaseous 2-CEES is detectable within 10 min, and the lowest detectable concentration is 10 ppb or less. Further experiments have shown that there exists an optimal CuO coating thickness which is about 6 nm. The CuO coating-based capture of 2-CEES molecules is attributed to the surface hydroxyl-induced specific adsorption, which is subject to the pseudo-second-order kinetics and Freundlich-typed model. This study presents the practical SERS chips and new route for the trace detection of gaseous sulfur-mustard.

7.
J Viral Hepat ; 28(10): 1355-1361, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34185938

RESUMO

We studied the characteristics of immune activation and investigated the underlying mechanisms in patients with human immunodeficiency virus-1/hepatitis B virus (HIV/HBV) coinfection after receiving HBV-active antiretroviral therapy. Forty patients with HIV/HBV coinfection, 38 patients with HIV monoinfection and 20 healthy controls were enrolled. CD4+ count, HIV load, HBV load, markers of immune activation and regulatory T-cell (Treg cell) frequency were assessed and compared between HIV-monoinfected and HIV/HBV-coinfected patients at week 0 (baseline), 12, 24, 36 and 48 after the onset of HBV-active antiretroviral therapy. Before antiretroviral therapy, frequencies of CD4+ HLADR+ CD38+ , CD8+ HLADR+ CD38+ , and Treg cells, and sCD163 and sCD14 levels were significantly higher in both HIV/HBV-coinfected patients and HIV-monoinfected patients, compared with healthy controls. Frequencies of CD4+ HLADR+ CD38+ and CD8+ HLADR+ CD38+ cells decreased following antiretroviral therapy in both groups. sCD163 levels did not change significantly in both groups and no significant difference was observed between the two groups at each time point during the 48-week antiretroviral therapy. In week 24, levels of sCD14 and frequencies of Treg cells appeared significantly higher in HIV/HBV-coinfected patients than in HIV-monoinfected patients, in which sCD14 levels and Treg cell frequencies declined to those in healthy controls. The Treg cell frequency was consistent with that of sCD14 levels in HIV/HBV-coinfected patients. Coinfection with HBV significantly increases sCD14 levels in HIV-infected patients during HBV-active antiretroviral therapy, which may potentially contribute to liver inflammation.


Assuntos
Coinfecção , Infecções por HIV , HIV-1 , Contagem de Linfócito CD4 , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Vírus da Hepatite B , Humanos , Linfócitos T Reguladores
8.
Front Cell Infect Microbiol ; 11: 625461, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777838

RESUMO

Background: Talaromycosis (TM) caused by Talaromyces marneffei (T. marneffei) is a growing public health concern. Although Toll-like receptor (TLR) genes play a critical role in the host defense against fungal infection, the influence of polymorphisms in these genes on the susceptibility of acquired immune deficiency syndrome (AIDS) patients to TM remains unknown. This study aims to uncover the associations of single nucleotide polymorphisms (SNPs) in TLR genes with TM susceptibility among patients with AIDS. Methods: Altogether 200 AIDS patients complicated with TM, 200 matched AIDS patients without TM, and 76 healthy controls (HCs) were enrolled in this case-control study. In total, 23 SNPs in the TLR2, TLR4, and TLR9 genes, which may influence the susceptibility of AIDS patients to TM, were checked by the time of flight mass spectrometry (TOF/MS) method among these Han Chinese subjects. Results: No significant differences in genotype or allele frequencies of selected SNPs were found among the TM group, Non-TM group, and HC group. Haplotype analysis also demonstrated no correlation of these SNPs with TM. However, subgroup analysis showed that the genotype TT and the T allele in TLR2 SNP rs1339 were more frequent in typical TM cases than controls (50.0 vs. 35.8%, 70.5 vs. 59.7%); the frequency of the GT genotype in TLR2 SNP rs7656411 was markedly higher in severe TM cases compared to controls (57.8 vs. 34.4%). Conclusion: Our results demonstrate a genetic connection of TLR2 SNPs rs1339 and rs7656411 with an increased susceptibility and severity of TM among Han Chinese populations.


Assuntos
Síndrome de Imunodeficiência Adquirida , Micoses , Estudos de Casos e Controles , China , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Talaromyces , Receptor 2 Toll-Like/genética , Receptor 3 Toll-Like , Receptor Toll-Like 9/genética
9.
Infect Genet Evol ; 91: 104781, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33639308

RESUMO

A retrospective analysis was conducted on HIV-infected patients whose continuously HAART strategy was lamivudine +tenofovir+ efavirenz. Propensity matching for 35 HBeAg-positive/HIV co-infected patients, 35 HBeAg-negative/HIV co-infected patients, and 70 HIV mono-infected patients. Immune recovery (including CD4 cells count, CD4/CD8 ratio, CD4 count multiples and CD4/CD8 multiples) of HBeAg-negative/HIV co-infected group are continuously lower than HBeAg-positive/HIV co-infected group and HIV mono-infected group. The result indicated that the mechanisms associated with HBeAg-negative may be involved in the regulation of immune recovery after HAART.

10.
Nanoscale Horiz ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33439211

RESUMO

Correction for 'Ultra-fast synthesis of water soluble MoO3-x quantum dots with controlled oxygen vacancies and their near infrared fluorescence sensing to detect H2O2' by Shichuan Zhong et al., Nanoscale Horiz., 2020, 5, 1538-1543, DOI: 10.1039/D0NH00394H.

11.
AIDS Res Hum Retroviruses ; 37(2): 157-161, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32873064

RESUMO

Multiple HIV-1 genotypes were found circulating in Guangdong Province, China, as this province is located in South China and has a high frequency of international trade. In this study, we report the near full-length genome (NFLG) of CRF12_BF that was identified from a male patient in Guangzhou city, Guangdong Province; this is the first time CRF12_BF has been reported in mainland China. The NFLG was amplified, and then PCR products were sequenced by Sanger sequencing. The CRF12_BF strain was confirmed by the Basic Local Alignment Search Tool and a neighbor-joining phylogenetic tree. In addition, this CRF12_BF strain was confirmed to contain the non-nucleoside reverse transcriptase inhibitor mutation E138A associated with potential low-level resistance against efavirenz and low-level resistance against rilpivirine by the Stanford University HIV Drug Resistance Database program. The analyzed sequence data in this study will provide more information on the HIV epidemic in China.

12.
J Med Virol ; 93(2): 794-802, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32672840

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in the intestines and feces, but its clinical significance is not completely clear. We aim to characterize the longitudinal test results of SARS-CoV-2 RNA in anal swabs and to explore the association with disease severity. METHODS: We included laboratory-confirmed coronavirus disease 2019 (COVID-19) patients, who were hospitalized in Guangzhou Eighth People's Hospital and excluded those who had not received anal swabs for SARS-COV-2 RNA testing. Epidemiological, clinical, and laboratory data were obtained. Throat swabs and anal swabs were collected periodically for SARS-COV-2 RNA detection. RESULTS: Two hundred and seventeen eligible patients (median aged 50 years, 50.2% were females) were analyzed. 21.2% (46/217) of the patients were detected with SARS-CoV-2 RNA in anal swabs. The duration of viral RNA was longer, but the viral load was lower in anal swabs than throat swabs in the early stage of the disease. During a median follow-up of 20 days, 30 (13.8%) patients were admitted to the intensive care unit (ICU) for high-flow nasal cannula or higher-level oxygen support measures to correct hypoxemia. Detectable viral RNA in anal swabs (adjusted hazard ratio [aHR], 2.50; 95% confidence interval [CI], 1.20-5.24), increased C-reactive protein (aHR, 3.14; 95% CI, 1.35-7.32) and lymphocytopenia (aHR, 3.12; 95% CI, 1.46-6.67) were independently associated with ICU admission. The cumulative incidence of ICU admission was higher among patients with detectable viral RNA in anal swabs (26.3% vs 10.7%, P = .006). CONCLUSION: Detectable SARS-CoV-2 RNA in the digestive tract was a potential warning indicator of severe disease.


Assuntos
Canal Anal/virologia , COVID-19/diagnóstico , Linfopenia/diagnóstico , RNA Viral/genética , SARS-CoV-2/genética , Adulto , Antivirais/uso terapêutico , Proteína C-Reativa/metabolismo , COVID-19/patologia , COVID-19/terapia , COVID-19/virologia , Teste para COVID-19 , Cloroquina/uso terapêutico , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Indóis/uso terapêutico , Unidades de Terapia Intensiva/estatística & dados numéricos , Linfopenia/patologia , Linfopenia/terapia , Linfopenia/virologia , Masculino , Pessoa de Meia-Idade , Oseltamivir/uso terapêutico , Faringe/virologia , Estudos Retrospectivos , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Carga Viral/efeitos dos fármacos
13.
Artigo em Inglês | MEDLINE | ID: mdl-33287631

RESUMO

The wide variety of new HIV-1 recombinant variants are a predominant challenge for understanding the molecular epidemiology and preventing the spread of the HIV-1 epidemic. In this study, we confirmed a novel HIV-1 unique B/C recombinant (ZLQ01186) isolated from a male patient infected with HIV-1 through injection drug use in Foshan city, Guangdong Province. The near full-length genome was amplified, and then the polymerase chain reaction products were sequenced by Sanger sequencing. The genomic sequence of the strain, with two subtype B segments inserted into the subtype C backbone, was 8,953 bp in length, extending from 647 to 9,599 bp according to the HXB2 genome. In addition, this B/C recombinant strain contained the non-nucleoside reverse transcriptase inhibitor resistance mutation K103N and the integrase strand transfer inhibitor other resistance mutation L74I according to the Stanford University HIV Drug Resistance Database program. The drug resistance profile indicates high-level resistance against efavirenz and rilpivirine. This study identified a recombinant between the main circulating strains, indicating a more complicated trend of the HIV-1 epidemic in Guangdong, China.

14.
J Infect Chemother ; 27(2): 218-225, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33039268

RESUMO

INTRODUCTION: Data on comprehensive characterization of multidrug-resistant (MDR) Staphylococcus aureus (S. aureus) carriage in human immunodeficiency virus (HIV)-positive patients are limited. The objective of the present study is to determine the prevalence, risk factors, phenotypic and molecular characterization of MDR S. aureus isolated from HIV-positive population. METHODS: A cross-sectional study was conducted to determine the characteristics of MDR S. aureus nasal carriage among HIV-positive outpatients in an HIV clinic from June to August 2017. Nasal swabs and risk factor data of the enrolled HIV-positive outpatients were collected. Phenotypic and molecular characteristics of MDR and non-MDR S. aureus isolates were analyzed. Risk factors for nasal carriage with MDR S. aureus were estimated by logistic regression. The relationship between phenotypic and molecular characteristics of S. aureus isolates was assessed by the correspondence analysis. RESULTS: Overall, 1001 HIV-positive outpatients were included. The prevalence of MDR S. aureus nasal carriage was 15.18% (152/1001), and the proportion of multidrug resistance among S. aureus isolates was 60.08% (152/253). Having a history of respiratory tract infection was the risk factor for MDR S. aureus nasal carriage (adjusted odds ratio = 1.90, 95% confidence interval: 1.25-2.89). Multidrug resistance of S. aureus isolates was in good corresponding relationships with clonal complex (CC)5, CC15, CC59 and CC398. CONCLUSIONS: We found high burden of multidrug resistance among S. aureus isolated from HIV-positive outpatients, particularly in those who had upper respiratory tract infection. Moreover, CC59 and CC398 are highly related to multidrug resistance of S. aureus isolates.


Assuntos
Infecções por HIV , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/uso terapêutico , Portador Sadio/epidemiologia , China/epidemiologia , Estudos Transversais , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Pacientes Ambulatoriais , Prevalência , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/genética
15.
Infect Genet Evol ; 87: 104673, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33309773

RESUMO

Guangzhou city is the political, economic, and cultural center of the Guangdong Province, China. The molecular epidemiological characteristics of HIV-1 in Guangzhou are not widely known. The aim of this study was to explore the characteristics of HIV-1 genotypes among treatment naïve HIV/AIDS patients living in Guangzhou. HIV-1 RNA was extracted from serum specimens. The partial pol gene of the HIV-1 genome was amplified and sequenced. The genotypes were screened using the subtyping tool COMET and further confirmed by phylogenetic analysis, with the exception of the URFs that were analyzed by jpHMM and RIP. The distributions of HIV genotypes in different risk populations were analyzed. Subsequently, pol sequences were used to construct transmission networks and analyze drug resistance. Twelve HIV-1 genotypes including 3 subtypes and 9 CRFs, with several URFs were identified from 1388 HIV-1 sequences, which were derived from 1490 patients. The main genotypes circulating in Guangzhou were CRF07_BC (38.3%), CRF01_AE (32.3%), and CRF55_01B (10.7%). CRF01_AE was the secondary dominant strain and multiple lineages of CRF01_AE had been identified in Guangzhou. The 01B recombinant forms, including CRF55_01B, CRF59_01B and CRF68_01B, have circulated widely in Guangzhou. 42.22% (586/1388) of the study sequences fell into 143 transmission networks, and the three main clusters revealed that sequences from MSM and HET populations were intermixed. 5.40% (75/1388) of patients had pre-treatment drug resistance. The HIV-1 strains that were present in Guangzhou have demonstrated complex genotypes. Particular attention should be given on these genotypes for the further strategy of prevention and intervention of HIV transmission.

16.
Diagn Progn Res ; 4(1): 19, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33292789

RESUMO

BACKGROUND: HIV/AIDS remains a leading cause of death worldwide. Recently, a model has been developed in Wenzhou, China, to predict the survival of people living with HIV/AIDS (PLWHA) who underwent antiretroviral therapy (ART). We aimed to evaluate the methodological quality and validate the model in an external population-based cohort. METHODS: Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess the risk of bias of the Wenzhou model. Data were from the National Free Antiretroviral Treatment Program database. We included PLWHA treated between February 2004 and December 2019 in a tertiary hospital in Guangzhou city, China. The endpoint was all-cause deaths and assessed until January 2020. We assessed the discrimination performance of the model by Harrell's overall C-statistics and time-dependent C-statistics and calibration by comparing observed survival probabilities estimated with the Kaplan-Meier method versus predicted survival probabilities. To assess the potential prediction value of age and gender which were precluded in developing the Wenzhou model, we compared the discriminative ability of the original model with an extended model added with age and gender. RESULTS: Based on PROBAST, the Wenzhou model was rated as high risk of bias in three out of the four domains (selection of participants, definition of outcome, and methods for statistical analysis) mainly because of the misuse of nested case-control design and propensity score matching. In the external validation analysis, 16758 patients were included, among whom 743 patients died (mortality rate 11.41 per 1000 person-years) during follow-up (median 3.41 years, interquartile range 1.64-5.62). The predictor of HIV viral load was missing in 14361 patients (85.7%). The discriminative ability of the Wenzhou model decreased in the external dataset, with the Harrell's overall C-statistics being 0.76, and time-dependent C-statistics dropping from 0.81 at 6 months to 0.48 at 10 years after ART initiation. The model consistently underestimated the survival, and the level was 6.23%, 10.02%, and 14.82% at 1, 2, and 3 years after ART initiation, respectively. The overall and time-dependent discriminative ability of the model improved after adding age and gender to the original model. CONCLUSION: The Wenzhou prognostic model is at high risk of bias in model development, with inadequate model performance in external validation. Thereby, we could not confirm the validity and extended utility of the Wenzhou model. Future prediction model development and validation studies need to comply with the methodological standards and guidelines specifically developed for prediction models.

18.
Chin Med J (Engl) ; 133(24): 2919-2927, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33252379

RESUMO

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Adulto , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , China , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Humanos , Maleimidas , Peptídeos , Ritonavir/uso terapêutico , Resultado do Tratamento , Carga Viral
19.
Virology ; 551: 26-35, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33011520

RESUMO

BACKGROUND: SARS-CoV-2 is a novel coronavirus and the cause of COVID-19. More than 80% of COVID-19 patients exhibit mild or moderate symptoms. In this study, we investigated the dynamics of viral load and antibodies against SARS-CoV-2 in a longitudinal cohort of COVID-19 patients with severe and mild/moderate diseases. METHODS: Demographic and clinical information were obtained. Serial samples of blood, nasal and pharyngeal and anal swabs were collected at different time points post-onset. SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies were measured by qRT-PCR and immunoassays, respectively. RESULTS: Respiratory SARS-CoV-2 RNA was detectable in 58.0% (58/100) COVID-19 patients upon admission and lasted for a median of 13 days post-onset. In addition, 5.9% (1/17) and 20.2% (19/94) of the blood and anal swab specimens were positive for SARS-CoV-2 RNA, respectively. Anal viral RNA was more frequently detected in the patients who were positive for viral RNA in the respiratory samples upon admission. Specific anti-SARS-CoV-2 antibody developed within two weeks after onset, reached peak approximately 17 days post-onset and then maintained at relatively high level up to 50 days we analyzed in most patients. However, the levels of antibodies were variable among the patients. High titers of antibodies appeared to be associated with the severity of the disease. Furthermore, viral proteins from different sources showed significant difference of serological sensitivity especially during the first week post-onset. CONCLUSIONS: Our results indicate rapid clearance or self-elimination of viral RNA in about half of the COVID-19 patients upon admission. Viral RNA shedding of SARS-CoV-2 occurred in multiple tissues including the respiratory system, blood, and intestine. Variable levels of specific anti-SARS-CoV-2 antibody may be associated with disease severity. These findings have shed light on viral kinetics and antibody response in COVID-19 patients and provide scientific evidence for infection control and patient management.


Assuntos
COVID-19/virologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Adulto , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , COVID-19/sangue , COVID-19/diagnóstico , Feminino , Humanos , Cinética , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , RNA Viral/análise , SARS-CoV-2/isolamento & purificação , Carga Viral , Eliminação de Partículas Virais
20.
JMIR Mhealth Uhealth ; 8(10): e20847, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-33118956

RESUMO

BACKGROUND: Associations between higher levels of patient engagement and better health outcomes have been found in face-to-face interventions; studies on such associations with mobile health (mHealth) interventions have been limited and the results are inconclusive. OBJECTIVE: The objective of this study is to investigate the relationship between patient engagement in an mHealth intervention and depressive symptoms using repeated measures of both patient engagement and patient outcomes at 4 time points. METHODS: Data were drawn from a randomized controlled trial (RCT) of an mHealth intervention aimed at reducing depressive symptoms among people living with HIV and elevated depressive symptoms. We examined the association between patient engagement and depressive symptoms in the intervention group (n=150) where participants received an adapted cognitive-behavioral stress management (CBSM) course and physical activity promotion on their WeChat social media app. Depressive symptoms were repeatedly measured using the Patient Health Questionnaire (PHQ-9) at baseline and 1 month, 2 months, and 3 months. Patient engagement was correspondingly measured by the completion rate, frequency of items completed, and time spent on the program at 1 month, 2 months, and 3 months. Latent growth curve models (LGCMs) were used to explore the relationship between patient engagement and depressive symptoms at multiple time points in the intervention. RESULTS: The mean PHQ-9 scores were 10.2 (SD 4.5), 7.7 (SD 4.8), 6.5 (SD 4.7), and 6.7 (SD 4.1) at baseline, 1 month, 2 months, and 3 months, respectively. The mean completion rates were 50.6% (SD 31.8%), 51.5% (SD 32.2%), and 50.8% (SD 33.7%) at 1, 2, and 3 months, respectively; the average frequencies of items completed were 18.0 (SD 14.6), 32.6 (SD 24.8), and 47.5 (SD 37.2) at 1, 2, and 3 months, respectively, and the mean times spent on the program were 32.7 (SD 66.7), 65.4 (SD 120.8), and 96.4 (SD 180.4) minutes at 1, 2, and 3 months, respectively. LGCMs showed good model fit and indicated that a higher completion rate (ß at 3 months=-2.184, P=.048) and a greater frequency of items completed (ß at 3 months=-0.018, P=.04) were associated with fewer depressive symptoms at 3 months. Although not significant, similar trends were found in the abovementioned relationships at 1 and 2 months. There was no significant relationship between time spent on the program and depressive symptoms. CONCLUSIONS: This study revealed a positive association between patient engagement and health outcomes at 3 months of an mHealth intervention using LGCMs and repeated measures data. The results underscore the importance of improving patient engagement in mHealth interventions to improve patient-centered health outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; https://tinyurl.com/yxb64mef. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-018-5693-1.


Assuntos
Infecções por HIV , Telemedicina , Depressão/epidemiologia , Depressão/terapia , Exercício Físico , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Humanos , Participação do Paciente
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