Adult ; Blood Donors ; Hepacivirus ; drug effects ; genetics ; Hepatitis C, Chronic ; virology ; Humans ; Interferons ; pharmacology ; Middle Aged ; Viral Load

BACKGROUNDThe efficacy and safety evidence of bortezomib in multiple myeloma (MM) patients with hepatitis B is vacant. This study aimed to investigate the efficacy and safety of bortezomib in MM patients with hepatitis B in China.

METHODSFrom 2006 to 2011, 739 newly diagnosed MM patients were screened for serum hepatitis B virus (HBV) biomarkers. HBV-infected patients were followed for HBV reactivation by monitoring of serum alanine transaminase (ALT) and HBV DNA load. The pattern of HBV reactivation in relation to bortezomib was evaluated. Seven hundred thirty-nine MM patients were included in this study.

RESULTSThe prevalence of MM patients infected with HBV was 3.4% (n = 25), of which 17 cases were treated with bortezomib. Bortezomib had no significant influence on liver function (ALT before and after treatment: 36.69 ± 8.90 U/L vs. 11.31 ± 2.74 U/L, P = 0.19) and HBV DNA of MM patients with HBV (detectable HBV DNA percentage: 5.9% vs. 11.8%, P = 0.12).

CONCLUSIONSBortezomib can be used safely and effectively in MM patients with hepatitis B. HBV prophylaxis and surveillance are recommended during the MM treatment.

Aged ; Antiviral Agents ; therapeutic use ; Bortezomib ; therapeutic use ; DNA, Viral ; drug effects ; genetics ; Female ; Hepatitis B ; drug therapy ; virology ; Hepatitis B virus ; drug effects ; pathogenicity ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; virology ; Retrospective Studies ; Viral Load

OBJECTIVETo review the recent literatures related to the factors associated with the size of the HIV reservoir and their clinical significance.

DATA SOURCESLiteratures related to the size of HIV DNA was collected from PubMed published from 1999 to June 2016.

STUDY SELECTIONAll relevant articles on the HIV DNA and reservoir were collected and reviewed, with no limitation of study design.

RESULTSThe composition and development of the HIV-1 DNA reservoir in either treated or untreated patients is determined by integrated mechanism comprising viral characteristics, immune system, and treatment strategies. The HIV DNA reservoir is a combination of latency and activity. The residual viremia from the stochastic activation of the reservoir acts as the fuse, continuing to stimulate the immune system to maintain the activated microenvironment for the rebound of competent virus once treatment with antiretroviral therapy is discontinued.

CONCLUSIONThe size of the HIV-1 DNA pool and its composition has great significance in clinical treatment and disease progression.

Anti-HIV Agents ; therapeutic use ; DNA, Viral ; genetics ; Female ; HIV Infections ; drug therapy ; genetics ; HIV-1 ; drug effects ; genetics ; pathogenicity ; Humans ; Male ; Viral Load ; drug effects ; genetics ; Viremia ; drug therapy ; genetics

OBJECTIVETo investigate drug resistance status in patients with highly active antiretroviral therapy (HAART) in Shandong province.

METHODSA total of 758 patients were separated from the anticoagulatory whole blood during May and October in 2011. The entire protease gene and part of the reverse transcriptase gene were amplified by RT-PCR and nest-PCR in the samples with viral load larger than 1000 copies/ml, then sequenced the gene fragments. Mutation of drug resistant gene and drug susceptibility was analyzed by the online tool HIV db program developed by Stanford University.

RESULTSThe rate of virologic failure in patients was 9.1% (69/758). A total of 53 gene sequences that acquired were used for genotypic resistance analysis. A total of 23 patients were indicated drug resistance with the total of 3.1% (23/742). Drug resistance rates of nucleotide reverse transcriptase inhibitor (NRTI) and non-NRTI(NNRTI) were 2.4% (18/742) and 3.0% (22/742), respectively, and the primary mutation types of drug resistance were M184V and Y181C for NRTI and NNRTI, with no resistance to protease inhibitor (PI). In the 23 patients indicated drug resistance, 78.3% (18/23) were NRTI resistance, 95.7% (22/23) were NNRTI resistance and 73.9% (17/23) dual NRTI and NNRTI resistance.

CONCLUSIONThe presence of drug resistant gene in HIV strains among AIDS patients with HAART in Shandong province was at low level, but mutation diversity was found in drug resistant gene.

Acquired Immunodeficiency Syndrome ; drug therapy ; virology ; Adolescent ; Adult ; Aged ; Antiretroviral Therapy, Highly Active ; Drug Resistance, Viral ; genetics ; Female ; Genes, Viral ; Genotype ; HIV-1 ; drug effects ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Sequence Analysis ; Viral Load ; Young Adult

OBJECTIVETo investigate the impact of heroin for antiviral treatment, drug resistance, mutation types and frequency in HIV/AIDS patients in Guangxi Zhuang Autonomous Region.

METHODSHIV/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.

RESULTSFor 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).

CONCLUSIONUsing 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.

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

OBJECTIVETo investigate the relationship between lamivudine-resistant mutants of hepatitis B virus (HBV) and serum HBV DNA loading before antiviral therapy.

METHODSThis study involved 106 patients with hepatitis B receiving lamivudine treatment for an average of 32 months (rang 12-48 months). Serum HBV DNA loadings were measured with PCR before and every 4 to 6 months during lamivudine therapy. HBV YMDD mutants were detected using mismatched PCR-restriction fragment length polymorphism (PCR-RFLP) during lamivudine treatment.

RESULTSHBV DNA loading was significantly higher in patients infected with HBV YMDD mutants during lamivudine therapy than those infected with HBV without YMDD mutation.

CONCLUSIONHigh viral loading in hepatitis B patients before treatment is associated with high likeliness of HBV YMDD mutation during lamivudine treatment. HBV DNA loading may be indicative for the occurrence of YMDD mutation during lamivudine therapy.

Antiviral Agents ; pharmacology ; DNA, Viral ; blood ; Drug Resistance, Viral ; genetics ; Female ; Hepatitis B ; blood ; Hepatitis B virus ; drug effects ; genetics ; physiology ; Humans ; Lamivudine ; pharmacology ; Male ; Middle Aged ; Mutation ; Viral Load ; genetics

BACKGROUND: Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. METHODS: A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA)-mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. RESULTS: The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ± 0.02] × 10vs. 1.00 ± 0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ± 0.12, vs.1.00 ± 0.37, t = 2.42, P < 0.05) and viral replication ([6.18 ± 0.95] × 10vs. 1.00 ± 0.43, t = 3.98, P < 0.05). CONCLUSIONS Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.
Betacoronavirus ; drug effects ; genetics ; Cell Line ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; drug therapy ; Drug Approval ; Humans ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; RNA, Small Interfering ; genetics ; Real-Time Polymerase Chain Reaction ; Viral Load

OBJECTIVETo investigate the effect of long-term highly active antiretroviral therapy (HAART) on the abnormal activation state and immune reconstitution in HIV-1 infected individuals.

METHODSCD4(+)T, CD8(+)T, CD8(+) CD38(+)T, CD8(+)HLADR(+)T and NK cell counts in the peripheral blood of 55 cases of HIV-1 infected individuals were measured by flow cytometry before and after HAART, and 30 healthy individuals served as controls.

RESULTCompared to healthy individuals, the CD4(+)T and NK cells decreased (P < 0.05) and CD8(+)T and CD8(+)HLADR(+)T cells increased significantly (P < 0.05) in HIV-1 infected individuals before HAART. After HAART, CD4(+)T and NK cells were recovered (P < 0.05), but still lower than normal (P < 0.05); CD4(+)T cell count in HIV-1 infected individuals remained stable at 1, 3 and 5 years after treatment, there were no significant differences among each groups; NK cell count had a downward trend with HAART (P < 0.05), there were statistical differences between 1-year and 5-year-HAART groups(P < 0.05). CD8(+)HLADR(+)T cells decreased promptly (P < 0.05), there were statistical differences between before and after HAART groups, 1-year and 5-year, 3-year and 5-year HAART groups (P < 0.05). CD8(+)CD38(+)T cells declined slowly, with no statistical differences amont each groups.

CONCLUSIONHAART can effectively reduce abnormal immune activation in HIV-1 infected individuals and achieve immune reconstitution to a certain degree.

Adult ; Antiretroviral Therapy, Highly Active ; Case-Control Studies ; Female ; Follow-Up Studies ; HIV Infections ; drug therapy ; immunology ; HIV-1 ; Humans ; Lymphocyte Activation ; drug effects ; Male ; Middle Aged ; T-Lymphocytes ; drug effects ; immunology ; Viral Load ; drug effects ; Young Adult

OBJECTIVETo investigate the progression and drug resistance of long-term non-progressors during three follow-up in Henan province.

METHODSIn May 2009, 26 cases of long-term non-progressors were recruited who infected HIV more than 10 years with blood collection and supply routes, did not receive anti-retroviral therapy, CD4(+)T lymphocyte count ≥350/μl and did not show typical symptoms of AIDS from Weishi, Shangcai, and Linying of Henan Province. Continuous follow-up were conducted three times since 2009 every two years with cohort analysis, the epidemiological information of infection routes, infection time and blood were collected, and 78 parts of 10 ml EDTA anticoagulated whole blood were collected. The changes of CD4 (+) T lymphocytes, viral load, and virus gene variety were characterized from 2009 to 2014. In-house methods were used to explore primary drug resistance of long-term non-progressors. Nonparametric Kruskal-Wallis test were used to compare CD4(+) T lymphocyte count and viral load changes during different follow-up times.

RESULTSThe average age and infection time of 26 cases were (48.51 ± 6.75) years, (13.42 ± 4.26) years, respectively. Three follow-up times, CD4(+) T lymphocyte count P50 (P25-P75) was 573.5 (487.4-789.8), 499.8 (403.5-635.7), and 418.8 (297.6-537.8)/μl (H=63.99,P<0.001), respectively. And natural logarithm of viral load P50 (P25-P75) were 3.93 (3.43-4.55), 4.29 (3.78-4.75), 4.50 (4.01-4.81) (H=3.19,P=0.355), respectively. Subtype and phylogenetic analysis of HIV showed that prevalent cases were B subtype, accounting for 88.5% (23/26), and three cases showed restructuring changes. Two cases appeared highly resistant of 18 infected patients whose viral load >1 000 copies/ml.

CONCLUSIONThe CD4(+)T lymphocyte had a declining trend, virus subtype recombinant changes in a few cases, and primary drug resistance was found of long-term non-progressors in Henan province.

Adult ; CD4 Lymphocyte Count ; China ; Cohort Studies ; Disease Progression ; HIV ; classification ; drug effects ; HIV Infections ; epidemiology ; HIV Long-Term Survivors ; Humans ; Middle Aged ; Phylogeny ; Viral Load

OBJECTIVETo understand the effect of highly active antiretroviral therapy (HAART) on AIDS patients, and to explore the prevalence and the impact of HIV-1 drug resistance in Shandong province.

METHODS2 cross-sectional studies were carried on in 2004 and 2005, to collect data on clinical symptoms and compliance of the AIDS patients with HAART through questionnaire. Informed-consent principle was followed to test on immunological, viral and laboratory index of them. HIV-1 drug genotype resistance by sequencing the gene of HIV-POL after RT-PCR was performed and analyzed.

RESULTS31 AIDS cases with and. 27 AIDS cases without HAART, were studied. 83.3% and 64.5% of the AIDS patients with HAART showed that the CD4+ T cell count was rising to over 350/microl, in the first study (2004) and in the second (2005) study respectively but still 45.8% and 45.2% of AIDS patients under HAART in the 2 years showed a decreasing HIV load under the detected limit. However, these findings were showing remarkable difference when compared with the AIDS without HAART. 7 drug resistance gene sites were found in AIDS patients with HAART and in AIDS patients without HAART. The rate on high degree drug resistance mutation and total drug resistance rate of mutation of the former were higher remarkably than those of the latter.

CONCLUSIONMost of the AIDS patients with HAART met the purpose of rebuilding immunity and control of HIV,as well as alleviation of symptoms. Although the drug resistance stain appeared in Shandong,but had little effect on HAART. AIDS; Drug resistance; Highly active antiretroviral therapy

Acquired Immunodeficiency Syndrome ; drug therapy ; Adult ; Antiretroviral Therapy, Highly Active ; CD4 Lymphocyte Count ; China ; Cross-Sectional Studies ; Drug Resistance, Viral ; genetics ; Genotype ; HIV-1 ; drug effects ; genetics ; Humans ; Middle Aged ; Patient Compliance ; Prevalence ; Surveys and Questionnaires ; Viral Load