Features of Ebola Virus Disease at the Late Outbreak Stage in Sierra Leone: Clinical, Virological, Immunological, and Evolutionary Analyses.

We performed Ebola virus disease diagnosis and viral load estimation for Ebola cases in Sierra Leone during the late stage of the 2014-2015 outbreak (January-March 2015) and analyzed antibody and cytokine levels and the viral genome sequences. Ebola virus disease was confirmed in 86 of 1001 (9.7%) patients, with an overall case fatality rate of 46.

Design, synthesis, and biological evaluation of novel trifluoromethyl indoles as potent HIV-1 NNRTIs with an improved drug resistance profile.

A novel series of trifluoromethyl indole derivatives have been designed, synthesized and evaluated for anti-HIV-1 activities in MT-2 cells. The hydrophobic constant, acute toxicity, carcinogenicity and mutagenicity were predicted. Trifluoromethyl indoles 10i and 10k showed extremely promising activities against WT HIV-1 with IC50 values at the low nanomolar level, similar to efavirenz, better than nevirapine, and also possessed higher potency towards the drug-resistant mutant strain Y181C than nevirapine.

Diverse reactivity in microwave-promoted catalyst-free coupling of substituted anilines with ethyl trifluoropyruvate and biological evaluation.

Diverse reactivity by coupling of substituted anilines with ethyl trifluoropyruvate was developed under microwave irradiation without catalysts to generate 3-trifluoromethyl-3-hydroxy oxindoles, aromatic hydroxy trifluoromethyl esters, and 1,2-dicarbonyl compounds in a fast and efficient manner. The plausible mechanism for obtaining different products was proposed. Furthermore, the anti-HIV activity of aromatic hydroxy trifluoromethyl esters was first reported.

Similar neutralizing activity in the HIV-1 infected long term non-progressors(LTNPs) and typical progressors(TPs).

Neutralizing antibodies are considered to be an important protective parameter used in HIV-1 vaccine evaluation. However, the exact role that neutralizing antibodies plays in controlling the disease progression of HIV-1 infected peoples is still undetermined. In this paper, we compared the protective function of the neutralizing antibody response in the plasma from LTNP and TP against clade B and clade C pseudoviruses.

[Prevalence status and mutation pattern of H221Y in subtype B' of HIV-1].

Objective: To explore the prevalence and mutation pattern of H221Y at reverse transcriptase (RT) among the subtype B' of human immunodeficiency virus1 (HIV-1) in antiviral therapy-failure patients.

Methods: A total of 1363 sequences, comprising of 1205 therapy-failure individuals and 158 therapy-naive individuals, were submitted to the Stanford HIV drug resistance database (SHDB) to analyze the frequency and mutation pattern of H221Y.

Results: The prevalence of mutation H221Y in the therapy-failure population was significantly higher than that of the therapy-naive (6.

[Studying on the prevalence and mutation pattern of N348I which related to the resistance of HIV-1].

Objective: To elucidate the prevalence and the mutation pattern of N348I that related to the resistance seen in the AIDS patients, in China.

Methods: Partial pol gene of HIV-1 comprising of full protease (PR) and reverse transcriptase (RT) was obtained from plasma samples of therapy-failure individuals (n = 614) and therapy-naive individuals (n = 619) by using reverse transcription polymerase chain reaction (RT-PCR). 1233 sequences were then submitted to the HIV-1 drug resistance database of the Stanford University to analyze the prevalence and the emergence pattern of N348I.

Allele-specific real-time PCR testing for minor HIV-1 drug resistance mutations: assay preparation and application to reveal dynamic of mutations in vivo.

Background: It is very important for the clinical management to test for minor HIV-1 resistance mutations accurately and sensitively. The conventional genotypic assays of HIV drug resistance detection based on sequencing can only discriminate the mutations which present in more than 20% - 30%. The aim of this study was to evaluate allele-specific real-time PCR (ASPCR) to detect the resistance-related mutations located at positions 103, 184 and 215.

[Antiviral effect of lamivudine on HIV-1 targeting MT2 cells influenced by morphine].

Objective: To determine whether morphine having the ability to influence the antiviral effect of lamivudine (3TC) in vitro study.

Methods: MT2 cells were randomly assigned into morphine + 3TC treatment group, morphine + naloxone + 3TC treatment group, naloxone + 3TC treatment group. Both 3TC and virus control groups were set up.

[Occurrence of human immunodeficiency virus-1 resistance through a six-year surveillance in rural areas of Henan].

Objective: To analyze the occurring rules of human immunodeficiency virus (HIV) drug resistance under an unique therapy model among HIV-1 infected individuals on antiretroviral therapy (ART) in rural areas of Henan, China.

Methods: A cohort of 75 individuals on an ART regimen of zidovudine (ZDV), dideoxyinosine (ddI) and nevirapine (NVP) was established in March 2003. A total of 12 surveillance were conducted and 788 person-times were studied until 2010.

[Screening program on novel drug resistance mutations of subtype B' in human immunodeficiency virus type 1 in China].

Objective: To screen the level of novel drug resistance mutations in subtype B' in China.

Methods: 451 pol sequences collected from the previous study, which including 354 AIDS patients who had received antiretroviral treatment (ART) and 97 the untreated patients. Entire protease gene (codons 1 - 99) and full-length reverse transcriptase gene (codons 1 - 560) were included.

[In vitro selection and identification of HIV strain which is resistance to two new HIV-1 nonnucleoside reverse transcriptase inhibitors].

JB25 and JB26 are new HIV-1 nonnucleoside reverse transcriptase inhibitors, and show potent anti-HIV activities. Sequential passage experiments with wild-type virus were performed to select and identify mutations induced by these two compounds in vitro. For the initial passage, compounds were present at approximately 2-fold IC50 in MT-2 cells.

A few specialized issues that should be focused on anti-HIV drug evaluation in vitro.

Since the introduction of antiretroviral therapy (ART), the lifespan and quality of life of patients infected with HIV have been significantly improved. But treatment efficacy was compromised eventually by the development of resistance to antiretroviral drugs, and more new anti-HIV drugs with lower toxicity and higher activity were needed. Based on the experience and lessons learned from the treatment in the developed countries, US FDA suggested that more pharmacodynamical researches should be considered ahead of the clinical trials.

Indinavir resistance evolution in one human immunodeficiency virus type 1 infected patient revealed by single-genome amplification.

Unlabelled: Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundamental to analyze the mechanism of drug resistance and develop a strategy to minimize resistance.

Immunogenicities of Env glycoproteins from circulating HIV-1 isolates in China focusing on the strategy of "DNA prime plus protein boost".

Background: The adenovirus-based HIV-1 vaccine developed by Merck Company suffered from an unexpected failure in September 2007. This generated a big shift in the strategy of HIV vaccine development with renewed focus on the induction of neutralizing antibodies. A major challenge in developing an HIV-1 vaccine is to identify immunogens and adopt delivery methods that can elicit broadly neutralizing antibodies against primary isolates of different genetic subtypes.

Competitive capacity of HIV-1 strains carrying M184I or Y181I drug-resistant mutations.

Background: Virus with nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs) resistant mutations show different evolution tendencies when the anti-viral therapies are interrupted. Understanding the replication fitness of drug-resistant virus is important for the study of the prevalence of drug-resistance. For this purpose, we characterized the replication capacity of HIV-1 virus carrying lamivudine (3TC) or nevirapine (NVP) resistant mutations.

[Research on the selective kinetics of HIV-1 nucleoside reverse transcriptase inhibitor drug resistance-associated mutations among 4 AIDS patients receiving highly active antiretroviral therapy].

Objective: To elucidate the molecular evolutional characteristics of HIV-1 nucleoside reverse transcriptase inhibitor (NRTI) drug resistance-associated mutations in patients with AIDS receiving highly active antiretroviral therapy.

Methods: We selected 4 AIDS patients receiving highly active antiretroviral therapy (HAART) with good adherence under a HIV-1 drug resistance cohort from a rural region in central China. Those people carried susceptible virus at the beginning of treatment and gradually came to produce virus resistant to NRTIs during the process of antiretroviral therapy (ART).

[Study on the difference of the APOBEC3G mRNA levels among HIV long-term nonprogressors, slow progressors, people at high risks and normal people].

Objective: To examine the APOBEC3G (hA3G) mRNA levels of four different groups in the human immunodeficiency virus (HIV) prevalent areas in central China and to analyze the relationship between hA3G mRNA levels and HIV disease progression.

Methods: We collected peripheral blood and isolated the peripheral boold monouuclear cells (PBMCs), and then cryo-preserved the PBMCs in liquid nitrogen. Prior to the total extraction of RNA, PBMCs were resuscitated and mRNA were reverse Transcripted to cDNA in vitro.

[Study on the antiviral therapy program among people with human immunodeficiency virus in Guangxi Zhuang Authority].

Objective: To explore the reconstitution of immune function and viral suppression condition and to analyze the occurrence of drug resistance HIV-1 variants and its prevalence after using HAART in Guangxi Autonomy Region.

Methods: From July 2004 to October 2005, 133 HIV infected individuals who had received HAART for more than three months were recruited, and 58 infected persons with no antiviral therapy were selected as controls. Questionnaire was used to collect information about the adherence of HAART therapy.

Phenotypic resistance of resistant strains of HIV type-1 subtype B in China.

Background: This study was aim to explore the characteristics of phenotypic resistance of resistant strains of HIV type-1 (HIV-1) subtype B and to compare the concordance between the phenotypic resistance and genotypic resistance.

Methods: The genotypic resistance assay for the HIV-1 clinical isolates was performed. One isolate without resistance mutation was chosen as a drug-sensitive reference strain and seven subtype B isolates with resistance mutations were phenotypically tested.

[Cohort study on human immunodeficiency virus discordant couples in the countryside of central China].

Objective: To establish a cohort of human immunodeficiency virus (HIV) discordant couples for follow-up studies and to collect data on frequency of HIV heterosexual transmission and related factors.

Methods: A total of 52 HIV discordant couples were identified by face to face interview and serological testing, in which the HIV negative individuals had no HIV infection behaviors including injecting drug use, blood transfusion or having sexual partners other than his/her own wife/husband. Three times of follows-up studies were carried out in 0.

Prevalence and evolution of drug resistance HIV-1 variants in Henan, China.

To understand the prevalence and evolution of drug resistant HIV strains in Henan China after the implementation of free antiretroviral therapy for AIDS patients. 45 drug naïve AIDS patients, 118 AIDS patients who received three months antiretroviral therapy and 124 AIDS patients who received six months antiretroviral treatment were recruited in the southern part of Henan province. Information on general condition, antiretroviral medicines, adherence and clinical syndromes were collected by face to face interview.

[Genotypic antiretroviral resistance testing and phylogenetic analysis of protease and reverse transcriptase in antiretroviral drug-naïve AIDS patients in Henan province].

Objective: Frequency, type and clinical implications on protease and reverse transcriptase drug resistance mutations were investigated and phylogenetic analysis in antiretroviral drug-naïve AIDS patients was carried out in Henan province.

Methods: 45 plasma samples were separated from the anticoagulatory whole blood, from which reverse transcription-polymerase chain reaction technique was used to amplify the partial pol gene. The sequences were analysed for genotypic antiretroviral resistance and phylogenetic relation through landing the websites http://hivdb.

[Cloning and characterization of a full-length HIV-1 genome of a prevalent subtype B-Thai strain in Henan Province].

Objective: To clone, identify and phylogenetically characterize a clade B-Thai HIV isolate representing the most prevalent virus in Henan province.

Methods: Peripheral blood mononuclear cells (PBMCs) from an HIV-1 infected patient in Henan Province were separated, and co-cultivated with phytohemagglutinin-stimulated healthy donor PBMCs. Proviral DNA was extracted from productively infected PBMCs.

[Study on factors associated with heterosexual-transmission of human immunodeficiency virus in central China].

Objective: To investigate the factors of the human immunodeficiency virus (HIV) associated with sexual-transmission in central China.

Methods: (1) Cross-sectional study: couples that one was HIV positive were selected in Henan and Hebei province of China. The couples must be 20 - 50 years old with normal function on sexual intercourse.