HIV-1 trans-activator of transcription (Tat) plays a critical role in HIV-1 transcription. Based on the beta-turn motif present in HIV-1 Tat, a series of novel benzodiazepine analogs were designed as beta-turn mimetics and prepared from p-chloro-nitrobenzene/2-phenylacetonitrile, p-toluidine/benzoyl chloride, or (Z)-7-nitro-5-phenyl-1H-benzo[e][1, 4]diazepin-2(3H)-one (nitrazepam) through different synthetic routes. Preliminary biological evaluation indicated that compound 30 exhibited inhibitory activity on HIV-1 tat-mediated LTR transcription with EC50 of 25.0 micromol x L(-1) and showed no obvious cytotoxic effects on TZM-BI cells under the concentration of 100 micromol x L(-1).
Benzodiazepinones ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; HIV Long Terminal Repeat ; genetics ; HIV-1 ; genetics ; Humans ; Transcription, Genetic ; drug effects ; tat Gene Products, Human Immunodeficiency Virus ; antagonists & inhibitors

Objective To study the correlation between high-resolution HLA-A * 1101,HLA-A * 0201,HLA-A * 2402,HLA-B * 4001,HLA-DRB1 * 0901 with HCMV pp65 antigenemia after bone marrow transplantation (BMT) in China.Methods 48 recipients doing BMT during 2009.2-2010.10 were selected in my hospital; HCMV pp65 was detected by ELISA or immunohistochemical methods.The frequency of HLA-A * 1101,HLA-A * 0201,HLA-A * 2402,HLA-B * 4001,HLA-DRB1 * 0901 alleles were determined by Polymerase chain reaction-sequence based typing( PCR - SBT).Results ① The BMT recipients were HCMV pp65 antigenic positive( 100％ ) ; ② The positive rate of HLA-A * 1101,HLA-A * 0201,HLA-A *2402,HLA-B * 4001 showed no obvious difference between 12 lower antigenemia group and 36 higher antigenemia group,the positive rate: HLA-A * 1101 were 33.3％ (8/24)and 20.8％ (15/72),HLA-A * 0201 were 4.2％ (1/24) and 13.9％ ( 10/72),HLA-A * 2402 were 12.5％ (3/24) and 19.4％ ( 14/72),HLA-B * 4001 were 16.7％ (4/24) and 12.5％ ( 9/72 ) ; ③ HLA-DRB1 * 0901 positive rate in higher antigenemia group was higher than the lower ( P =0.048 ),the positive rate were 4.2％ ( 1/24 ) and 19.4％ (14/72) ;④ HLA-DRB1 * 0901 recipients were higher pp65 antigenemia than HLA-A * 2402 recipients (P=0.007) and HLA-A * 1101 recipients (P =0.028),HLA-A * 0201 recipients were higher pp65 antigenemia than HLA-A * 2402 ( P =0.02),the pp65 antigenemia showed no obvious difference among the rest of high-resolution HLA groups (P ＞ 0.05).Conclusion HLA-DRB1 * 0901 alleles might be correlated with BMT recipients happened higher pp65 antigenemia,HLA-A * 2402 alleles might be correlated with BMT recipients happened lower pp65 antigenemia.

BACKGROUNDCD4 count is used to determine antiretroviral therapy (ART) eligibility. In China, flow cytometers are mostly located in urban areas with limited access by patients residing in remote areas. In an attempt to address this issue, we conducted a study to validate the performance of Alere PIMA point-of-care CD4 analyzer.

METHODSVenous and finger-prick blood specimens were collected from HIV-positive participants from two voluntary counseling and testing sites in Yunnan Province. Both venous and finger-prick blood specimens were tested with the PIMA analyzer. Venous blood specimens tested with the Becton Dickinson FACSCalibur were used as a reference.

RESULTSVenous specimens from 396 and finger-prick specimens from 387 persons were available for analysis. CD4 counts by PIMA correlated well with those from FACSCalibur with an R2 of 0.91 for venous blood and 0.81 for finger-prick blood. Compared to FACSCalibur, the PIMA analyzer yielded lower counts with a mean bias of - 47.0 cells/μl (limit of agreement, [LOA]: -204-110 cells/μl) for venous blood and -71.0 cells/μl (LOA: -295-153 cells/μl) for finger-prick blood. For a CD4 threshold of 350 cells/μl, the positive predictive value (PPV) of PIMA was 84.2% and 75.7% and the negative predictive value (NPV) was 97.6% and 95.8% for venous and finger-prick blood, respectively. For an ART threshold of 500 cells/μl, the corresponding PPV was 90.3% and 84.0% and NPV was 94.3% and 93.4%, respectively.

CONCLUSIONSCD4 counting using venous blood with PIMA analyzers is a feasible alternative to a large flow cytometer to determine ART eligibility.

Adolescent ; Adult ; Aged ; Biological Assay ; methods ; Blood Specimen Collection ; CD4 Lymphocyte Count ; methods ; Child ; China ; Female ; HIV Infections ; diagnosis ; Humans ; Male ; Middle Aged ; Sensitivity and Specificity ; Young Adult