Efficacy and Safety of Tenofovir and Lamivudine in Combination with Efavirenz in Patients Co-infected with Human Immunodeficiency Virus and Hepatitis B Virus in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China. Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV.</p><p><b>METHODS</b>One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen of TDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed.</p><p><b>RESULTS</b>Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%). Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml·min-1·1.73 m-2) to week 12 (104 ml·min-1·1.73 m-2) but was almost back to baseline at week 48 (111 ml·min-1·1.73 m-2).</p><p><b>CONCLUSION</b>This combination ART regimen is safe and effective for patients with HIV/HBV co-infection.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov, NCT01751555; https://clinicaltrials.gov/ct2/show/NCT01751555.</p>

Comparison of fluorescence quantitative PCR and direct PCR sequencing in the detection of HBV polymerase RT region / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the feasibility of Direct PCR sequencing in clinic and the significance of Direct PCR sequencing for retrieval treatment plan.</p><p><b>METHODS</b>To address this issue, a cross-sectional study on the drug resistance in the HBV polymerase RT region was performed using Fluorescence quantitative PCR and Direct PCR sequencing in 60 chronic hepatitis B patients, who responded failure to long-term LAM and/or ADV therapy.</p><p><b>RESULT</b>Compared with Fluorescence quantitative PCR, Direct PCR sequencing expressed a higher positive rate (43.2% vs 38.6%; 66.7% vs 54.2%, respectively) and a lower missing rate (9.5% vs 19.0%; 5.9% vs 23.5%, respectively) in the detection of drug resistance in the patients treated with LAM or combination therapy of LAM with ADV. The sensitivity of experiment using Direct PCR sequencing seemed better than Fluorescence quantitative PCR, although the difference was not significant. Further analysis on sensitivity and specificity of detection between high and low viral loads groups indicated that the consensus of two experiments in high viral load group is better than that in low viral load group (Chi-square test = 5.18, probability value = 0.023). In low viral load group, Direct PCR sequencing expressed higher sensitivity and higher specificity than Fluorescence quantitative PCR, although the difference did not approach significant.</p><p><b>CONCLUSION</b>Direct PCR sequencing is better than Fluorescence quantitative PCR in the detection of drug resistance in clinic, not only with higher sensitivity and specificity, but also with comprehensive information of HBV polymerase RT region.</p>

Expression and purification of TAT-HBX-EGFP fusion protein and its transmembrane distribution in mouse / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To highly express TAT-HBX-EGFP fusion protein and study its distribution in mouse liver.</p><p><b>METHODS</b>TAT-HBX-EGFP recombinant vector was constructed and fusion protein was induced by IPTG and expression in BL21; fusion protein was purified by Ni-NTA argarose, then injected into the peritoneal cavity of the mice. Distribution of fusion protein was observed by immunofluorescence.</p><p><b>RESULTS</b>TAT-HBX-EGFP was highly expression in E. coli; HBX could be induced into mouse liver by TAT.</p><p><b>CONCLUSION</b>HBX protein could be induced into mouse liver by TAT induced peptide.</p>

Virological and immunological outcomes in HIV-1-infected Chinese patients treated with a combination of Efavirenz and Indinavir for 48 weeks / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The incidence of HIV-1-related infection diseases and the mortality of AIDS have dramatically decreased since highly active antiretroviral therapy began to be used clinically in China in 1999. And we initiated a second clinical trial using a combination of Efavirenz and Indinavir to observe the effects of the immunoreaction.</p><p><b>METHODS</b>Twenty patients with laboratory-confirmed chronic HIV-1 infection were recruited. Blood samples were collected initially and during the weeks after initiation of treatment. Within 48 hours of blood sampling, peripheral blood plasma and mononuclear cells were separated using routine methods. HIV-1 viral load was measured in thawed plasma samples. Within 48 hours of peripheral blood sampling, CD4(+) and CD8(+) T cell subsets were enumerated.</p><p><b>RESULTS</b>The drug regimen was efficient in reducing HIV-1 plasma viral load and increasing total CD4(+) T cell counts. The percentage of CD4(+) and CD8(+) T cell subsets expressing CD38 and HLA-DR activation markers was positively correlated with plasma viral load and tended to normalize.</p><p><b>CONCLUSIONS</b>The combination of Efavirenz and Indinavir was generally well tolerated and efficient at reducing HIV-1 RNA. Furthermore, the treatment improved the immunological function.</p>

Study on the distribution of human immunodeficiency virus-1 subtypes in different regions of China and mother-to-child transmission / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the distribution of human immunodeficiency virus (HIV)-1 genotypes in major prevalent regions of China and to illustrate the relationship between HIV-1 subtypes and mother-to-child transmission in a retrospective cohort.</p><p><b>METHODS</b>HIV-1 gag p17 and env C2-V4 region were amplified by nested-polymerase chain reaction (nPCR) and the sequences were obtained by sequencing gag nPCR products or clones of env gene.</p><p><b>RESULTS</b>60 HIV-1 positive individuals were subject to typing for gag p17 and 69 for env C2-V4 region. Single clade was only found in Henan (subtype B') and Xinjiang (subtype C), and subtypes C and E were demonstrated in Yunnan. These regions represented most of the HIV-1 infections in China. Multiple subtypes (A, B, C, E, etc.) were found in Beijing and Shanghai, where HIV infections were still in low level. The sequences of subtype C were less diversive in Xinjiang (p17: 0.0192 +/- 0.0078, C2-V4: 0.0455 +/- 0.0145) than in Yunnan (p17: 0.0279 +/- 0.0102, C2-V4: 0.0482 +/- 0.0171), but all of them clustered in "C" branch in phylogenetic trees. Trafficking of subtype C from Yunnan to Xinjiang was found but had already been reported by others. Compared to subtype C, subtype E was quite divergent (p17: 0.0473 +/- 0.0105, C2-V4: 0.1114 +/- 0.0112) in Yunnan, but no recombination was found in the C2-V4 region of env gene. Highe divergence of subtype B' was found in Henan and the peripheral provinces (p17: 0.0381 +/- 0.0101, C2-V4: 0.0691 +/- 0.0166), which might be attributed to the early epidemics of HIV-1 in these areas (early 1990's). In maternal-child cohort, subtypes B (7/21), C (11/21), E (1/21) and undefined types (2/21) were identified in non-transmitting HIV-1 positive mothers, while only subtype B (7/11) and C (4/11) appeared in transmitting HIV-1 positive mothers. The rate of transmission was 53.8% (7/13) in mothers infected with subtype B and 30.8% (4/13) in those infected with subtype C, but with no significant difference (P = 0.196). The imbalancing distribution of subtypes might be explained by the fact that transfusion or illegal blood would increased mother-to-child transmission on HIV-1 and most of mothers with clade B were infected by illegal blood transfusion in this cohort. In addition, most of the maternal-child pair's sequences clustered in gag or env phylogenetic trees but only a few did disperse among the unrelated patients because children were older (>/= 4 years).</p><p><b>CONCLUSION</b>The characteristics of HIV-1 clade's distribution differed over most parts of China but no difference was demonstrated between subtype B and C in mother-to-child transmission on HIV-1.</p>

Study on the epidemiology and distribution of human immunodeficiency virus-1 and hepatitis C virus infection among intravenous drug users and illegal blood donors in China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To determine the epidemiologic features and distribution of human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) infection among intravenous drug users and illegal blood donors in China.</p><p><b>METHODS</b>Polymerase chain reaction (PCR) amplification and DNA sequencing were used to evaluate the HIV-1 gag p17 and env C2-V3 regions, as well as the HCV 5'NCR and E1/E2 regions.</p><p><b>RESULTS</b>Among 239 subjects with reported HIV-1 infection, 56.9% (136/239) were seropositive for anti-HCV. Of those, 96.3% (131/136) were co-infected with HCV through intravenous drug use and illegal blood donation. Intravenous drug users in Yunnan, Guangxi and Xinjiang provinces were infected with HIV-1 subtype C and HCV genotypes 1b, 3a, 3b and 4, whereas illegal blood donors in Henan province harbored HIV-1 subtype B' and HCV genotypes 1b and 2a. Five different HIV-1 subtypes were identified among 17 HIV-1-infected individuals from Beijing.</p><p><b>CONCLUSIONS</b>Multiple HIV-1 subtypes and HCV genotypes were identified in China which were associated with several different modes of transmission. Homogeneity within the sequences of the two viruses suggested the recent, but separate, outbreaks of HIV-1 and HCV infection. The distinct distribution patterns of HIV-1 and HCV genotypes in two high-risk groups seemed to be more closely linked to the mode of transmission than to geographic proximity.</p>