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1.
BMC Infect Dis ; 23(1): 144, 2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36890462

ABSTRACT

BACKGROUND: To understand the factors influencing clinical outcomes of severe hand, foot, and mouth diseases (HFMD), and to provide scientific evidence for reducing the mortality risk of severe HFMD. METHODS: From 2014 to 2018, children diagnosed with severe HFMD cases in Guangxi, China, were enrolled in this hospital-based study. The epidemiological data obtained through face-to-face interviews with the parents and guardians. Univariate and multivariate logistics regression models were used to analyze the factors influencing the clinical outcomes of severe HFMD. The impact of the EV-A71 vaccination on inpatient mortality was analyzed by a comparison approach. RESULTS: A total of 1565 severe HFMD cases were enrolled in this survey, including 1474 (94.19%) survival cases and 91 (5.81%) death cases. The multivariate logistic analysis demonstrated that HFMD history of playmates in the last three months, first visit to the village hospital, time from the first visit to admission less than two days, no correct diagnosis for HFMD at the first visit, and having no rash symptoms were the independent risk factors for severe HFMD cases (all p < 0.05). While EV-A71 vaccination was a protective factor (p < 0.05). The EV-A71 vaccination group versus the non-vaccination group showed 2.23% of death in the vaccination group and 7.24% of death in the non-vaccination group. The EV-A71 vaccination protected 70.80% of the death of severe HFMD cases, with an effective index of 4.79. CONCLUSIONS: The mortality risk of severe HFMD in Guangxi was related to playmates had HFMD history in last 3 months, hospital grade, EV-A71 vaccination, patients visit hospital previously, and rash symptom. EV-A71 vaccination can significantly reduce mortality among severe HFMD. The findings are of great significance for the effective prevention and control of HFMD in Guangxi, southern China.


Subject(s)
Enterovirus A, Human , Enterovirus , Exanthema , Hand, Foot and Mouth Disease , Mouth Diseases , Child , Humans , Infant , Hand, Foot and Mouth Disease/epidemiology , China/epidemiology , Hospitals
2.
BMC Med Genomics ; 16(1): 59, 2023 03 25.
Article in English | MEDLINE | ID: mdl-36966292

ABSTRACT

The risk of severe condition caused by Corona Virus Disease 2019 (COVID-19) increases with age. However, the underlying mechanisms have not been clearly understood. The dataset GSE157103 was used to perform weighted gene co-expression network analysis on 100 COVID-19 patients in our analysis. Through weighted gene co-expression network analysis, we identified a key module which was significantly related with age. This age-related module could predict Intensive Care Unit status and mechanical-ventilation usage, and enriched with positive regulation of T cell receptor signaling pathway biological progress. Moreover, 10 hub genes were identified as crucial gene of the age-related module. Protein-protein interaction network and transcription factors-gene interactions were established. Lastly, independent data sets and RT-qPCR were used to validate the key module and hub genes. Our conclusion revealed that key genes were associated with the age-related phenotypes in COVID-19 patients, and it would be beneficial for clinical doctors to develop reasonable therapeutic strategies in elderly COVID-19 patients.


Subject(s)
COVID-19 , Physicians , Humans , COVID-19/genetics , Cell Differentiation , Gene Expression Profiling , Phenotype , Gene Regulatory Networks
3.
China Tropical Medicine ; (12): 473-2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-979737

ABSTRACT

@#Abstract: Objective To explore the spatial epidemiological characteristics of severe cases hand, foot and mouth disease (HFMD) in Guangxi, China, from 2014 to 2018, and to provide a basis for identifying the high-risk regions as well as the prevention and control of severe cases of HFMD in Guangxi. Methods Spatial-temporal scanning analysis, global and local spatial autocorrelation analysis were used to analyze the spatial clustering of HFMD. The trend surface analysis was used to evaluate the spatial distribution trend of HFMD. Results From 2014 to 2018, the incidence and severe case fatality rates of HFMD were 3.89/100 000 and 4.23%, respectively. Monte Carlo scanning analysis showed that the first cluster region was Cenxi City, the second cluster was mainly concentrated in northwest of Guangxi, and the aggregation time was mainly concentrated in April to May and August to October. The global spatial autocorrelation analysis showed that the severe HFMD was significant clustering distribution, and the Moran's I coefficients of the sever cases, severe morbidity and severe case fatality rate were 0.088, 0.118, 0.197, respectively (P<0.05). Local spatial autocorrelation analysis showed that hotspots of severe HFMD cases were concentrated in the southern Guangxi, mainly in Lingshan County. Anselin local Moran's I clustering and outlier analysis indicated that 5 high-high (H-H) clustering regions for fatality were Lingshan, Pubei, Zhongshan, Zhaoping and Pinggui County. There were 6 high-high (H-H) clustering regions for severe incidence rate, namely Lingshan, Qinnan, Lingyun, Youjiang, Bama Yao Autonomous and Pinggui County, and 1 high-low (H-L) clustering region, Cenxi County. The trend surface analysis showed that the overall number of severe cases of death decreased from east or west to the middle, and increased from north to middle, and then decreased to south. Conclusions Severe HFMD cases in Guangxi have obvious spatial-temporal clustering, and the hop spots are mainly concentrated in southern Guangxi. The prevention and control of HFMD in areas with high incidence of severe cases should be strengthened to reduce the burden of HFMD cases.

4.
BMC Infect Dis ; 22(1): 471, 2022 May 16.
Article in English | MEDLINE | ID: mdl-35578187

ABSTRACT

BACKGROUND: Vaccination has been proven to be an effective approach against the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to determine the acceptance rate and factors influencing acceptance of COVID-19 vaccination among people living with HIV (PLWH) in Guangxi, China. METHODS: A cross-sectional survey was carried out in five cities in Guangxi, China from May 7 to June 1, 2021. Questionnaires on the acceptance of COVID-19 vaccination and the related factors were conducted among PLWH recruited by simple random sampling. Univariate and multivariate logistic regression analyses were performed to identify factors associated with acceptance of COVID-19 vaccination. RESULTS: Of all valid respondents (n = 903), 72.9% (n = 658) were willing to receive COVID-19 vaccination. Fear of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was the main reason for being willing to receive vaccination (76.0%), while the main reasons for not willing were the concerns about vaccine safety (54.7%) and the vaccination's effect on antiretroviral therapy (ART) (50.6%). The most important factors influencing acceptance were the perception that vaccination is unsafe for HIV-infected people (aOR = 0.082, 95% CI = 0.024-0.282) and the poor efficacy in preventing SARS-CoV-2 infection in HIV-infected people (aOR = 0.093, 95% CI = 0.030-0.287). Other factors associated with acceptance included Zhuang ethnicity (aOR = 1.653, 95% CI = 1.109-2.465), highest education level of middle school, high school or above (aOR = 1.747, 95% CI = 1.170-2.608; aOR = 2.492, 95% CI = 1.326-4.682), and the vaccination having little effect on ART efficacy (aOR = 2.889, 95% CI = 1.378-6.059). CONCLUSIONS: Acceptance rate of the COVID-19 vaccination is relatively low among PLWH compared to the general population in China, although some patients refused vaccination due to concerns about vaccine safety and vaccination affecting ART efficacy. More research is needed to investigate the impact of the COVID-19 vaccines on ART efficacy and the effectiveness in preventing SARS-CoV-2 infection among PLWH.


Subject(s)
COVID-19 , HIV Infections , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , China/epidemiology , Cross-Sectional Studies , Humans , SARS-CoV-2 , Surveys and Questionnaires , Vaccination
5.
Intervirology ; 65(1): 58-66, 2022.
Article in English | MEDLINE | ID: mdl-34186534

ABSTRACT

New kinds of HIV-1 circulating recombinant forms (CRFs) and unique recombinant forms (URFs) earn a great prevalence in China nowadays. In this study, we identified 2 similar URFs (2016GXNNIDU037 and 2019QZLSIDU253) both isolated from intravenous drug users (IDUs) in Guangxi, China. Phylogenetic analysis of the near full-length genome (NFLG) revealed 2 URFs both clustered with CRF01_AE but setting up a monophyletic branch, supporting a high bootstrap value. Bootscan analysis and subregional recombinant analysis found that the NFLG of 2016GXNNIDU037 and 2019QZLSIDU253 were both composed of CRF01_AE and CRF07_BC, with 3 CRF07_BC mosaic segments inserted into CRF01_AE backbones. The CRF01_AE segments of the 2 URFs clustered with a previously reported cluster 2 lineage of CRF01_AE. The 5 recombinant breakpoints of the 2 URFs were quite similar. Distinct from CRF01_AE/CRF07_BC URFs reported before, 2016GXNNIDU037 and 2019QZLSIDU253 are new evidence of a high genetic variety of HIV-1 in Guangxi, which may pose new challenges to HIV-1 prevention and molecular epidemiological surveillance in China.


Subject(s)
Drug Users , HIV Infections , HIV-1 , Substance Abuse, Intravenous , China/epidemiology , Genome, Viral , Genotype , HIV Infections/epidemiology , HIV-1/genetics , Humans , Phylogeny , Recombination, Genetic , Sequence Analysis, DNA , Substance Abuse, Intravenous/complications
6.
Front Immunol ; 13: 1020822, 2022.
Article in English | MEDLINE | ID: mdl-36685491

ABSTRACT

Background: The immune activation caused by microbial translocation has been considered to be a major driver of HIV infection progression. The dysbiosis of gut microbiota has been demonstrated in HIV infection, but the interplay between gut microbiota and its metabolites in the pathogenesis of HIV is seldom reported. Methods: We conducted a case-controlled study including 41 AIDS patients, 39 pre-AIDS patients and 34 healthy controls. Both AIDS group and pre-AIDS group were divided according to clinical manifestations and CD4 + T cell count. We collected stool samples for 16S rDNA sequencing and untargeted metabolomics analysis, and examined immune activation and microbial translocation for blood samples. Results: The pre-AIDS and AIDS groups had higher levels of microbial translocation and immune activation. There were significant differences in gut microbiota and metabolites at different stages of HIV infection. Higher abundances of pathogenic bacteria or opportunistic pathogen, as well as lower abundances of butyrate-producing bacteria and bacteria with anti-inflammatory potential were associated with HIV severity. The metabolism of tryptophan was disordered after HIV infection. Lower level of anti-inflammatory metabolites and phosphonoacetate, and higher level of phenylethylamine and polyamines were observed in HIV infection. And microbial metabolic pathways related to altered metabolites differed. Moreover, disrupted metabolites contributed by altered microbiota were found to be correlated to microbial translocation and immune activation. Conclusions: Metabolites caused by dysbiosis of gut microbiota and related metabolic function are correlated to immune activation and microbial translocation, suggesting that the effect of microbiota on metabolites is related to intestinal barrier disruption in HIV infection.


Subject(s)
Acquired Immunodeficiency Syndrome , Gastrointestinal Microbiome , HIV Infections , Humans , Gastrointestinal Microbiome/genetics , Acquired Immunodeficiency Syndrome/complications , Dysbiosis/microbiology , Anti-Inflammatory Agents/therapeutic use
7.
Front Immunol ; 12: 756288, 2021.
Article in English | MEDLINE | ID: mdl-34777369

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has caused many deaths worldwide. To date, the mechanism of viral immune escape remains unclear, which is a great obstacle to developing effective clinical treatment. RNA processing mechanisms, including alternative polyadenylation (APA) and alternative splicing (AS), are crucial in the regulation of most human genes in many types of infectious diseases. Because the role of APA and AS in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown, we performed de novo identification of dynamic APA sites using a public dataset of human peripheral blood mononuclear cell (PBMC) RNA-Seq data in COVID-19 patients. We found that genes with APA were enriched in innate immunity -related gene ontology categories such as neutrophil activation, regulation of the MAPK cascade and cytokine production, response to interferon-gamma and the innate immune response. We also reported genome-wide AS events and enriched viral transcription-related categories upon SARS-CoV-2 infection. Interestingly, we found that APA events may give better predictions than AS in COVID-19 patients, suggesting that APA could act as a potential therapeutic target and novel biomarker in those patients. Our study is the first to annotate genes with APA and AS in COVID-19 patients and highlights the roles of APA variation in SARS-CoV-2 infection.


Subject(s)
COVID-19/genetics , Polyadenylation , SARS-CoV-2 , Alternative Splicing , COVID-19/immunology , Female , Genome, Human , Humans , Immunity, Innate , Leukocytes, Mononuclear , Male , RNA, Messenger , Transcriptome
8.
Biomed Res Int ; 2020: 7857231, 2020.
Article in English | MEDLINE | ID: mdl-32626763

ABSTRACT

In recent years, the prevalence of human immunodeficiency virus (HIV) infection among Chinese university students has increased significantly, and HIV transmission among men who have sex with men (MSM) comprises more than half of the new cases. There is still a lack of research investigating the incidence of male-to-male sex, the attitudes towards MSM, and the awareness of HIV/AIDS among university students in Guangxi, one of the HIV high-risk areas in China. Therefore, we performed a cross-sectional investigation among 578 male students, recruited by stratified sampling, in universities in Nanning, Guangxi, between January 2016 and March 2017. Researcher-administered anonymous questionnaires were completed. Self-recognition as MSM was found in 8.48% of the subjects. Compared with non-MSM, university student MSM included more people over the age of 20 (OR = 4.95), had less migration from other districts of Guangxi (OR = 0.26), and the majority were nonmedical students (OR = 8.99). In total, 63.25% of the male student participants reported a lack of acceptance of MSM, while 35.47% acknowledged barriers between themselves and acquaintances who were MSM. Overall, 67.30% of the subjects correctly answered questions related to AIDS knowledge. The proportion of MSM subjects who answered the AIDS-related questions completely correctly was significantly lower than that of non-MSM subjects (42.86% vs. 69. 57%, respectively, OR: 0.33), but the self-recognition risk of MSM was significantly higher than that of non-MSM (OR = 2.59). Risky behaviors associated with HIV infections, including smoking, alcohol consumption, drug abuse, and inconsistent condom use, were significantly higher among the MSM participants. The percentages of student's willingness to accept MC and PrEP were 70.93% and 77.51%, respectively. These results raise the alarm that university student MSM in Guangxi, China, require urgent public attention and more effective health education, including the education on MC and PrEP.


Subject(s)
HIV Infections , Health Knowledge, Attitudes, Practice , Heterosexuality/statistics & numerical data , Homosexuality, Male/statistics & numerical data , Students , Adolescent , Adult , China/epidemiology , Cross-Sectional Studies , HIV Infections/psychology , HIV Infections/transmission , Health Risk Behaviors , Humans , Male , Students/psychology , Students/statistics & numerical data , Universities , Young Adult
9.
Front Immunol ; 11: 1050, 2020.
Article in English | MEDLINE | ID: mdl-32547554

ABSTRACT

Innate immunity is the first line of defense against invading pathogens and may mediate HIV-1 resistance in HIV-1-exposed seronegative (HESN) individuals. This study aims to identify components of innate immunity that confer natural HIV-1 resistance in Chinese HESN individuals. Specifically, we compared the expression levels of Toll-like receptors (TLRs) and associated pathway molecules in peripheral blood mononuclear cells (PBMCs), monocytes/macrophages, and plasma obtained from HESN and control individuals. HESN individuals had higher expression of TLR9, IRF7, IFN-α/ß, RANTES, and MIP-1α/1ß in PBMCs and plasma than control subjects. Upon TLR9 stimulation, significantly higher expression of TLR9 and IRF7, as well as higher production of IFN-α/ß, RANTES, and MIP-1α/1ß, was observed in PBMCs and monocytes/macrophages from HESN individuals than in the corresponding cells from control individuals. More importantly, both with and without TLR9 stimulation, the levels of HIV-1 replication in monocyte-derived macrophages (MDMs) from HESN individuals were significantly lower than those in MDMs from control individuals. These data suggest that increased TLR9 activity and subsequent release of antiviral factors contribute to protection against HIV-1 in HESN individuals.


Subject(s)
HIV Infections/metabolism , HIV-1/physiology , Toll-Like Receptor 9/metabolism , Adult , Cells, Cultured , China , Disease Resistance , Female , Gene Expression Regulation , HIV Seronegativity , Humans , Immunity, Innate , Interferon Regulatory Factor-7/metabolism , Male , Middle Aged , Signal Transduction , Young Adult
10.
AIDS Res Ther ; 17(1): 4, 2020 02 07.
Article in English | MEDLINE | ID: mdl-32033564

ABSTRACT

OBJECTIVES: For migrant female sex workers (FSWs) at the Sino-Vietnamese border, the impact of work time in their current location on the spread of HIV/AIDS is not clear. METHODS: Data were collected from the Sino-Vietnamese border cities of Guangxi, China. Migrant FSWs working in these cities were studied. FSWs who worked less than 6 months in their current location were assigned to the short-term work group (ST FSWs), and FSWs who worked equal to or longer than 6 months in their current location were assigned to the long-term work group (LT FSWs). Logistic regression was performed to examine the impact of work time in the current location and factors associated with HIV infection. RESULTS: Among the 1667 migrant FSWs, 586 (35.2%) and 1081 (64.9%) were assigned to the ST FSW and LT FSW groups, respectively. Compared to LT FSWs, ST FSWs were more likely to be of Vietnamese nationality, be less than 18 years old when they first engaged in commercial sex work, and have a low-level of HIV-related knowledge and had higher odds of using condoms inconsistently, having more male clients, having no regular male clients, and having a history of male clients who used aphrodisiacs but lower odds of receiving free condoms distribution and education/HIV counselling and testing programme. The analysis of factors associated with HIV infection revealed that Vietnamese FSWs, less than 18 years old when they first engaged in commercial sex work, having no regular male clients, and having lower average charge per sex transaction were correlated with HIV infection. CONCLUSION: FSWs with short-term work at the Sino-Vietnamese border had a higher risk of risky sex and were correlated with HIV risk factors. Vietnamese FSWs were at higher risk of HIV infection, and they were more likely to have short-term work. More targeted HIV prevention should be designed for new FSWs who recently began working in a locality to further control the spread of HIV, particularly cross-border FSWs.


Subject(s)
HIV Infections/transmission , Sex Workers/statistics & numerical data , Sexual Behavior/statistics & numerical data , Transients and Migrants/statistics & numerical data , Adult , China/epidemiology , Condoms , Cross-Sectional Studies , Female , HIV Infections/epidemiology , Humans , Male , Middle Aged , Prevalence , Risk Factors , Surveys and Questionnaires , Time Factors , Vietnam/epidemiology , Young Adult
11.
AIDS Res Ther ; 16(1): 6, 2019 03 16.
Article in English | MEDLINE | ID: mdl-30876476

ABSTRACT

OBJECTIVE: This study aimed to investigate the prevalence of HIV late presentation and advanced HIV disease and to identify the factors associated with HIV late presentation and advanced HIV disease among patients with newly diagnosed HIV/AIDS in the Guangxi Zhuang Autonomous Region, in Southwestern China. METHODS: Patients with newly diagnosed HIV registered in the HIV surveillance system of Guangxi Centers for Disease Control between January 2012 and December 2016 were included in this study. RESULTS: Of 45,118 newly diagnosed patients, 70.2% had late presentation, and 45.1% had advanced HIV disease. A higher prevalence of late presentation and advanced HIV disease was found in male heterosexuals and female people who use drugs (PWID). Heterosexuals (OR 2.11 [95% CI 1.90-2.34]) and PWID (OR 1.55 [95% CI 1.30-1.84]) had a higher risk of late presentation than men who have sex with men (MSM). Blood testing of the blood receivers (OR 1.75 [95% CI 1.36-2.26]) and diagnosed in hospital (OR 1.74 [95% CI 1.65-1.84]) had an increased risk of late presentation compared to those who diagnosis in voluntary counseling and testing (VCT). Heterosexuals (OR 2.86 [95% CI 2.51-3.27]), PWID (OR 2.23 [95% CI 1.83-2.71]), blood testing of the blood receivers (OR 1.58 [95% CI 1.29-1.94]) and diagnosed in hospital (OR 1.85 [95% CI 1.76-1.94]) were also independent risk factors associated with advanced HIV disease. Older age, lower level of education and being divorced or widowed were also associated with late presentation and advanced HIV disease. CONCLUSIONS: Late presentation and advanced HIV disease were very common among patients with newly diagnosed HIV in Guangxi, China during 2012-2016. Targeted programs are urgently required to reduce HIV late diagnosis in Guangxi, especially for male heterosexuals, PWID, and patients with characteristics such as older age, lower level of education, divorced or widowed.


Subject(s)
Delayed Diagnosis , Epidemiological Monitoring , HIV Infections/diagnosis , HIV Infections/epidemiology , Adolescent , Adult , Age Factors , China/epidemiology , Counseling , Cross-Sectional Studies , Drug Users , Female , Heterosexuality , Homosexuality, Male , Humans , Male , Middle Aged , Prevalence , Risk Factors , Sexual and Gender Minorities , Young Adult
12.
Sci Rep ; 7(1): 13071, 2017 10 12.
Article in English | MEDLINE | ID: mdl-29026137

ABSTRACT

The molecular mechanism of opiate use promoting HIV-1 infection is not fully understood. TLR9 is expressed in many immune cells, including monocytes, macrophages, which can recognize viruses and viral products and consequently induce the production of antiviral factors and initiate immune responses. Previous studies have shown that chronic viral infections can overcome and impair TLR9 pathway. We aimed to explore whether opiate use enhances HIV infection through inhibition of TLR9 pathway via a population-based study. A total of 200 subjects were enrolled and divided into four groups as follows: Opiate+ HIV+ (50), Opiate- HIV+ (50), Opiate+ HIV- (50), and healthy control (Opiate- HIV-, 50). All HIV-infected subjects did not receive antiretroviral therapy while they were enrolled in the study. The results showed that opiate use was associated with higher viral load and lower CD4+ T cell count. Opiate use alone led to lower expression of TLR9, IRF7, and IFN-α at the protein level in PBMCs. Combined with HIV-1 infection, opiate use resulted in lower expression of MyD88, ISG56, and MxA. In addition, morphine treatment promoted HIV-1 replication in macrophages via inhibition of TLR9 pathway. Our data reveal that opiate use plays a cofactor role in pathogenesis of HIV-1 infection through inhibition of TLR9 pathway.


Subject(s)
Antiviral Agents/pharmacology , HIV Infections/metabolism , HIV-1/drug effects , HIV-1/pathogenicity , Signal Transduction/drug effects , Toll-Like Receptor 9/metabolism , Virus Replication/drug effects , Analgesics, Opioid/pharmacology , Blotting, Western , CD4-Positive T-Lymphocytes/metabolism , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Humans , Methadone/pharmacology , Real-Time Polymerase Chain Reaction , Viral Load/drug effects
13.
Microb Drug Resist ; 23(3): 285-293, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27420739

ABSTRACT

Epidemiological studies have demonstrated that the human immunodeficiency virus (HIV)-1 drug-resistant rate among injecting drug users is higher than that in other HIV-1-positive populations, which is generally believed to be largely due to clinical nonadherence. Little is known, however, about whether heroin abuse has a direct impact on the generation of HIV-1 drug-resistant mutations. In this study, we investigated the impacts of morphine, the active metabolite of heroin, on HIV-1 infection/replication and HIV-1 drug-resistant mutations through an in vitro HIV-1-CD4+ T cell system under selective pressure from two typical antiviral drugs, Lamivudine and Nevirapine. We found that morphine treatment of MT4 cells (a CD4+ T cell line) significantly increased HIV-1 III B (a T-tropic viral strain) infection and replication in MT4 cells, and the effect of morphine on HIV-1 was mediated through an opioid receptor. More importantly, our results showed that morphine treatment not only induced more drug-resistant mutations under selective pressure from antiretroviral drugs but also shortened the mutations' generation time, compared with the control groups that were treated with antiretroviral drugs alone. Although the in vivo relevance remains to be determined, these findings provide direct in vitro evidence to support the possibility that heroin abuse itself can act as an independent factor contributing to the generation of HIV-1 drug resistance during clinical antiretroviral therapy. Therapeutic guidelines should consider this issue for heroin users with HIV infection.


Subject(s)
Drug Resistance, Viral/drug effects , HIV-1/drug effects , HIV-1/genetics , Lamivudine/pharmacology , Morphine/pharmacology , Mutation/drug effects , Nevirapine/pharmacology , Anti-HIV Agents/pharmacology , Cell Line , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , Humans , Mutation/genetics , Virus Replication/drug effects , Virus Replication/genetics
14.
Drug Alcohol Depend ; 159: 246-54, 2016 Feb 01.
Article in English | MEDLINE | ID: mdl-26790825

ABSTRACT

BACKGROUND: Although a number of in vitro studies have shown that methamphetamine (METH) can increase HIV-1 replication in human immune cells, a direct link between METH use and HIV-1 pathogenesis remains to be determined among HIV-1 patients. METHODS: According to the status of METH use and HIV-1 infection, we enrolled participants and divided them into four groups: METH+HIV+, METH-HIV+, METH+HIV-, and METH-HIV-. HIV viral loads and HIV-1-related cellular factors were measured and compared among different groups. RESULTS: A total of 60 participants were enrolled into this study, 15 within each group. HIV viral loads in METH+HIV+ group were significantly higher than those in METH-HIV+ group, while CD4+ T cell counts had an inverse trend between the two groups (p<0.05). METH users or HIV-1 infected patients had lower CCR5+, CXCR4+ percentages in CD4+ T cells than METH-HIV- subjects (p<0.01). However, METH use had little effect on CD3 expression in PBMCs and the levels of MIP-1α, MIP-1ß and IL-6 in PBMCs or plasma, which were increased by HIV-1 infection with or without METH. TLR-9 and IFN-α levels in PBMCs of METH users with or without HIV infection were higher than non-METH users (p<0.05). CONCLUSIONS: METH use is associated with higher viral loads and lower CD4+ T cell counts in HIV-infected individuals. This finding may be mediated by activation of innate immunity (TLR-9, IFN-α) by METH use.


Subject(s)
HIV Infections/virology , HIV-1/drug effects , HIV-1/growth & development , Methamphetamine/pharmacology , Viral Load/drug effects , Adult , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Chemokine CCL3/blood , Chemokine CCL3/metabolism , Chemokine CCL4/blood , Chemokine CCL4/metabolism , Down-Regulation , Female , HIV Infections/immunology , Humans , Immunity, Innate/drug effects , Interferon-alpha/biosynthesis , Interleukin-6/blood , Interleukin-6/metabolism , Male , Methamphetamine/urine , Middle Aged , Receptors, CCR5/biosynthesis , Receptors, CXCR4/biosynthesis , Toll-Like Receptor 9/biosynthesis
15.
Bing Du Xue Bao ; 31(2): 132-8, 2015 Mar.
Article in Chinese | MEDLINE | ID: mdl-26164937

ABSTRACT

The aim of this study was to investigate the influence of opiate abuse on the expression of Toll-like receptor 9 (TLR9) in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected patients and to elucidate possible mechanisms involved in the enhancement of HIV-1 replication by opiate abuse. A total of 200 participants were enrolled in the study by random selection from methadone treatment centers and voluntary HIV counseling and testing centers in the cities of Nanning, Liuzhou, and Qinzhou. These participants included 50 HIV-positive opiate abusers (Opiates HIV(+) group), 50 HIV-negative opiate abusers (Opiates HIV(-) group), 50 HIV-positive subjects who were not opiate abusers (Non-opiates HIV (+) group), and 50 HIV-negative subjects who were not opiate abusers (Control group). PBMCs were isolated from the peripheral blood samples from the subjects and the expression levels of TLR9 mRNA and protein were determined by q-PCR and western blot respectively. There was no significant difference among the four groups in age, gender, nationality, domicile, marital status, educational background or duration of drug abuse (P > 0.05). The median viral loads of the Opiates HIV(+) were significantly higher than those of the Non-Opiates HIV(+) groups (4.450 x 10(3) and 3.977 x 10(3) copies/mL respectively, P < 0.05). The relative expression levels of TLR9 mRNA in the Opiates HIV(+), Non-Opiates HIV(+), Opiates HIV(-) and Control groups were (2.13 +/- 1.59) x 10(-3), (3.66 +/- 2.22) x 10(-3), (1.96 +/- 1.42) x 10(-3) and (7.66 +/- 4.87) x 10(-3), respectively. The expression of TLR9 mRNA was significantly lower in both HIV-1-infected and -uninfected groups of opiate abusers compared with groups of non-abusers (P < 0.05). There was no significant difference in TLR9 mRNA expression levels between the Opiates HIV(+) group and the Opiates HIV(-) group (P > 0.05). However, in the non-opiate groups, the expression levels of TLR9 mRNA in the HIV(+) group were significantly lower than that of the control group (P< 0.05). Western blot results confirmed that the expression of TLR9 protein was lower in the Opiates HIV(+), Non-Opiates HIV(+), and Opiates HIV(-) groups compared to the control group. These results suggest that opiate abuse can decrease the expression of TLR9 in PBMCs, which may result in the enhancement of HIV-1 infection and replication due to a decline in immune response mediated by the TLR9 pathway.


Subject(s)
HIV Infections/genetics , Leukocytes, Mononuclear/metabolism , Opioid-Related Disorders/genetics , Toll-Like Receptor 9/genetics , Adolescent , Adult , Female , HIV Infections/metabolism , HIV Infections/virology , HIV-1/physiology , Humans , Male , Middle Aged , Opioid-Related Disorders/metabolism , Toll-Like Receptor 9/metabolism , Young Adult
16.
AIDS Res Hum Retroviruses ; 31(4): 439-47, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25420616

ABSTRACT

The purpose of this article is to describe mortality trends in different highly active antiretroviral therapy (HAART) periods and associated factors among AIDS patients in Guangxi, China. We prospectively analyzed AIDS patients in Guangxi between 2001 and 2011; demographic characteristics were compared among AIDS patients diagnosed in three treatment periods (pre-HAART: 2001-2004, early-HAART: 2005-2008, and late-HAART: 2009-2011). AIDS mortality was calculated by person-years, and treatment coverage was defined as the proportion of time that patients who were eligible for treatment received treatment. Factors of AIDS mortality were determined by a Cox proportional hazard regression. Of 19,020 AIDS patients, overall mortality declined from 41.1 per 100 person-years in 2001 to 13.3 per 100 person-years in 2011 with treatment coverage increasing from zero to 72.1%. The overall median survival figure was 5.6 years (95% CI: 4.4-6.8) with 60.3% for 5-year survival rate. After AIDS diagnosis, the mortality rate peaked in the first year, and 37.4% patients were still active in the ninth year. Protective factors for mortality were AIDS patients diagnosed from 2009 to 2011 (AHR=0.75, 95% CI: 0.58-0.89), having received HAART (AHR=0.71, 95% CI: 0.50-0.87), and having a CD4 count of higher than 350 cells/µl at AIDS diagnosis (AHR=0.79, 95% CI: 0.60-0.92). Risk factors for mortality included being male (AHR=1.28, 95% CI: 1.07-1.43), living in a rural area (AHR=1.40, 95% CI: 1.18-1.94), and being aged ≥60 years at AIDS diagnosis (AHR=1.36, 95% CI: 1.18-1.73). A decline in AIDS mortality was observed in Guangxi with a concomitant increase in treatment coverage. Some subpopulations of AIDS patients, such as males, rural residents, and the old, require more medical care.


Subject(s)
Acquired Immunodeficiency Syndrome/mortality , Acquired Immunodeficiency Syndrome/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , China/epidemiology , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Analysis , Young Adult
17.
Zhonghua Yu Fang Yi Xue Za Zhi ; 48(10): 851-6, 2014 Oct.
Article in Chinese | MEDLINE | ID: mdl-25573121

ABSTRACT

OBJECTIVE: To investigate the impact of heroin for antiviral treatment, drug resistance, mutation types and frequency in HIV/AIDS patients in Guangxi Zhuang Autonomous Region. METHODS: HIV/AIDS patients were recruited in Methadone Maintenance Treatment Clinics, HIV/AIDS Clinic and HIV Voluntary Counseling and Testing Center Liuzhou and Baise city from April 2008 to October 2009. The patients were grouped by the situation of antiviral treatment and use of heroin. A total of 435 HIV/AIDS patients were recruited, among which 108 cases in antiviral treatment and heroin group, 93 cases in antiviral treatment and never using drug group, 105 cases in no antiviral treatment and using heroin group, 129 cases in no antiviral treatment and never using drug group. The effect of antiviral treatment was evaluated by questionnaire survey, viral load measurement and CD4(+) T lymphocyte count. HIV-1 RNA from plasma was extracted, and then the pol genes were amplified and sequenced. The sequences were analyzed for HIV-1 genotype drug-resistance. RESULTS: For the patients who received antiviral treatment, the viral load in heroin group was higher than that in never using drug group (lg (2.61 ± 1.24) vs lg (2.08 ± 0.80), t = 3.54, P < 0.05) , and the percentage of viral load lower than 1 000 copies/ml in heroin group was significantly less than that in never using drug group (63.9% vs 86.0%,χ(2) = 12.76, P < 0.05). For the patients who received antiviral treatment, the difference has no significance in CD4(+) T lymphocyte count between heroin group and never using drug group ((337.92 ± 181.66) vs (326.14 ± 254.98), t = 0.38, P = 0.703). For the patients who didn't receive antiviral treatment, the difference also has no significance in CD4(+) T lymphocyte count between heroin group and never using drug group ((373.73 ± 155.97) vs (337.53 ± 209.26), t = 1.47, P = 0.143). For the patients who received antiviral treatment, there was no difference in the percentage of the CD4(+) T lymphocyte count more than 350/ml between heroin group and never using drug group (48.1% vs 43.0%, χ(2) = 0.53, P = 0.466). 319 HIV-1 pol gene sequences were obtained. Among the patients who received antiviral treatment, the mutation frequency of M184V/I, T215Y/F, L210W and T69N/S in heroin abuser group were significantly higher than that in never using drug group (14.9% (11/74) vs 4.4% (3/68), 12.2% (9/74) vs 1.5% (1/68), 12.2% (9/74) vs 1.5% (1/68) and 10.8% (8/74) vs 1.5% (1/68) respectively) (P < 0.05). CONCLUSION: Using heroin may promote HIV replication, reducing the virological response to antiviral treatment and increasing the frequencies of drug resistance loci among HIV/AIDS patients.Heroin rehabilitation may benefit from the antiviral treatment and obtain better antiviral effect.


Subject(s)
Acquired Immunodeficiency Syndrome , Anti-HIV Agents , Antiviral Agents , Drug Resistance, Viral , HIV Infections , Heroin/adverse effects , Mutation Rate , Mutation/drug effects , CD4 Lymphocyte Count , China , Drug Resistance , Genes, pol , HIV-1 , Heroin Dependence , Humans , Viral Load
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