ABSTRACT
Objective:To investigate the impact of low level viremia (LLV) on the prognosis of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients received anti-retroviral therapy (ART).Methods:From January to December 2015, the HIV/AIDS patients with LLV received ART over one year were recruited in Guangzhou Eighth People′s Hospital, Guangzhou Medical University (LLV group). Patients with viral load (VL) less than 50 copies/mL were matched at ratio of 1∶1 according to gender, age and the transmission route were included in the control group (suppression group). The LLV group was divided into three subgroups according to VL (LLV-1 subgroup was 50-200 copies/mL, LLV-2 subgroup was 201-400 copies/mL, and LLV-3 subgroup was 401-1 000 copies/mL). The influence of LLV on the antiviral response during the following three years was investigated.The Wilcoxon signed rank test, Kruskal-Wallis test and chi-square test were used for statistical analysis.Results:One hundred and thirty-seven patients were enrolled in the LLV group, of whom 111 were males and 26 were females, with age of (39.5±13.5) years old. At the same time, 137 patients were included in the suppression group. There were 93 cases in LLV-1 subgroup, 25 cases in LLV-2 subgroup and 19 cases in LLV-3 subgroup. There were no significant differences in the CD4 + T lymphocyte counts and CD4 + /CD8 + T lymphocyte counts ratios between LLV group and suppression group before ART (both P>0.05). During the three-year follow-up, the cumulative number of viral failures in LLV group (7.3%(10/137)) was significantly higher than that in the suppression group (1.5%(2/137)) ( χ2=5.578, P=0.018). Virological failure occurred in eight patients (8.6%) in the LLV-1 subgroup, two patients (8.0%) in the LLV-2 subgroup, and no patients in the LLV-3 subgroup. There was no statistical significance in the incidence of virological failure among all the subgroups ( P>0.05). At one, two, three years follow-up, the CD4 + T lymphocyte counts increased in both LLV group and suppression group without statistical differences (all P>0.05), and the CD4 + /CD8 + T lymphocyte counts ratios in each LLV group were lower than that in the suppression group ( Z=-3.183, -2.094 and -2.312, respectively, all P<0.05). At one, two, three years follow-up, There were no significant differences in CD4 + /CD8 + T lymphocyte counts ratios among the LLV-1, LLV-2 and LLV-3 subgroups (all P>0.05). Conclusion:HIV/AIDS patients with LLV having received ART over one year are more likely to develop virological failure and delay the recovery of immune function, which requires early relevant interventions.
ABSTRACT
Objective:To investigate the clinical characteristics and pathogen spectrum of acquired immunodeficiency syndrome (AIDS) patients complicated with pulmonary filamentous fungal infection in Guangdong Province, so as to provide evidences for improving the diagnosis and treatment.Methods:A total of 143 AIDS patients with pulmonary filamentous fungal infection hospitalized in Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 2016 to December 2018 were included. The filamentous fungi cultured in bronchoalveolar lavage fluid of these patients were identified with morphological and molecular biological methods. And their clinical characteristics were analyzed. Nonparametric Kruskal-Wallis H test and chi-square test were used for statistical analysis. Results:Among the 143 patients, 116(81.1%) had fever, 104(72.7%) had cough, 83(58.0%) had expectoration, and 59(41.3%) had anhelation. The CD4 + T lymphocyte count was 22.0(9.3, 60.8) cells/μL and 118(82.5%) cases were below 100.0 cells/μL. The white blood cell counts decreased in 52(36.4%) cases and increased in 18(12.6%) cases, anemia was found in 109(76.2%) cases, platelet count decreased in 29(20.3%) cases. Sixty-four (44.8%) cases were positive for galactomannan test. Chest computed tomography showed diffuse infection of both lungs in 114(79.7%) cases, miliary changes in 12(8.4%) cases, pleural effusion in 44(30.8%) cases, and enlargement of pleural and (or) mediastinal lymph nodes in 45(31.5%) cases. After receiving antifungal therapy, 124 (86.7%) cases were cured or improved, and 19 (13.3%) cases were discharged automatically or died of disease deterioration. Among the 143 strains of filamentous fungi, there were 56 strains of Aspergillus species pluralis (39.2%, including 24 strains of Aspergillus fumigatus), 37 strains of Talaromyces marneffei ( T. marneffei) (25.9%), 22 strains of Penicilium species pluralis (15.4%), and 28 strains of other genera of filamentous fungi (19.6%). The median CD4 + T lymphocyte counts in patients infected with Aspergillus species pluralis, T. marneffei, Penicilium species pluralis and other genera were 24.5, 15.0, 53.5 and 22.0 cells/μL, respectively, and the difference was statistically significant ( H=11.282, P=0.010). The proportions of AIDS patients with different pulmonary filamentous fungal infection of CD4 + T lymphocyte count ≤50.0 cells/μL in descending order were T. marneffei group (89.2%(33/37)), Aspergillus species pluralis group and other genera group (67.9%(38/56), 67.9%(19/28)), and Penicillium species pluralis group (54.5%(12/22)), and the difference was statistically significant ( χ2=9.296, P=0.026). Conclusions:The clinical manifestations of pulmonary filamentous fungal infection in AIDS patients in Guangdong Province are not specific. The pathogenic spectrum contains various genera, and T. marneffei and Aspergillus fumigatus are dominant, which could be correlated with CD4 + T lymphocyte count.
ABSTRACT
Objective:To analyze the dynamic changes of total HIV-1 DNA in peripheral blood mononuclear cells (PBMC) following highly active antiretroviral therapy (HAART) in HIV-1/HCV co-infected patients.Methods:Thirty patients with HIV-1/HCV co-infection without anti-HCV treatment (co-infected group) and 42 HIV-1 infected patients with initial treatment (mono-infected group) admitted to Guangzhou Eighth People’s Hospital from May 2015 to December 2017 were retrospectively analyzed. The virological and immunological responses of the two groups at 12, 24, 48, 72 and 96 weeks after HAART, the changes of total HIV-1 DNA in PBMC and its relationship with peripheral blood HIV-1 RNA and T lymphocyte subsets were observed. SPSS 22.0 statistical software was used to analyze the data.Results:The plasma HIV-1 virus inhibition rate, CD4 + T cells and CD4 + /CD8 + ratio increased and the total HIV-1 DNA in PBMC decreased in both groups after HAART. The inhibition rate of HIV RNA at week 72 in co-infected group was significantly lower than that in the mono-infected group ( χ2=7.93, P<0.01). Compared with the mono-infected group, the CD4 + T cells at week 12, 24, 72 and 96 after HAART were lower in the co-infected group ( U=313.50, 329.00, 286.00 and 204.50, P<0.05 or <0.01). The CD4 + /CD8 + ratio at week 48 in the co-infected group was lower than that in the mono-infected group ( U=294.50, P<0.05). The total HIV-1 DNA of the co-infected group at baseline and week 12 was lower than that of the mono-infected group ( U=362.00 and 359.00, P<0.01 or <0.05). There was no significant correlation between total HIV-1 DNA in PBMC and HIV-1 RNA or CD4 + /CD8 + ratio in both groups ( P>0.05). There was no correlation between total HIV-1 DNA and CD4 + T cells in HIV-1/HCV co-infected group ( b=-0.001, P>0.05), but it had negative correlation in the mono-infected group ( b=-0.001, P<0.05). Conclusion:Total HIV-1 DNA in PBMC was significantly decreased after HAART in HIV-1/HCV co-infected patients. Co-infected with HCV may delay the decrease of total HIV-1 DNA after HAART in patients with HIV-1 infection.
ABSTRACT
Objective@#To analyze the variation characteristics of HIV-1 Gp120 sequences in men who have sex with men (MSM) in Guangzhou.@*Methods@#Plasma samples were collected from HIV-1 infected MSM before antiretroviral treatment. Viral RNA was extracted from plasma. Gp120 gene sequences were amplified by reverse transcription and nested-PCR using specific primers. Phylogenetic tree, length polymorphism, amino acid characteristics of V3 loop, co-receptors and signature amino acids were analyzed.@*Results@#The phylogenetic tree were divided into 4 clusters, and the most prevalent subtypes were CRF07_BC (34/61, 55.74%) and CRF01_AE (24/61, 39.34%). Majority of HIV-1 Gp120 sequences had 496-515 amino acids. Among five hypervariable regions, the V1 region had the highest levels of length polymorphism and V3 region had the lowest. The top four peptide of V3 loop were GPGQ (56/58, 96.55%). Most of the co-receptors HIV-1 strains used was CCR5(50/58, 86.21%)according to four methods of comprehensive prediction. There are four signature amino acids in CRF01_AE subtype strains, and the frequency of occurrence was 0.75-0.83; there are eight signature amino acids in CRF07_BC subtype strains, and the frequency was 0.74-0.94.@*Conclusions@#The length of Gp120 sequences in MSM in Guangzhou has a high polymorphism. The top four peptide of V3 loop, co-receptor and signature amino acid of V3 ring have formed unique patterns.
ABSTRACT
Objective@#To analyze the characteristic mutations of epitopes in HBV Pre-S/S region in HIV/HBV co-infected patients’ peripheral blood to provide basic data for studying the pathogenesis of HIV/HBV co-infection.@*Methods@#The chronic hepatitis B infected patients admitted to the Infectious Disease Center of the Eighth People′s Hospital of Guangzhou from January 2009 to December 2011 were enrolled into HIV/HBV co-infected group and HBV mono-infected group according to the result of HIV antibody detection respectively before treatment. HBV DNA in serum was extracted and Pre-S/S region of HBV DNA was amplified by nested-PCR. After sequencing of the obtained PCR products (direct sequencing), ContigExpress software was used for sequence splicing and BioEdit software was used for sequence alignment. With reference to the standard sequence of the matched genotype HBV, mutants of HBV Pre-S/S region in HIV/HBV co-infected group and HBV mono-infected group were analyzed respectively. Statistical analysis was performed by chi-square test with SPSS19.0 statistical analysis software.@*Results@#HBV Pre-S/S fragments were successfully amplified from 150 patients, including 90 cases of HIV/HBV co-infected group and 60 cases of HBV mono-infected group, with matched gender, age, genotype, HBeAg status, alanine aminotransferase (ALT), aspartate aminotransferase (AST). The result of analyzing mutants of HBV Pre-S/S region indicated that the incidence of mutation in all epitopes for cytotoxic T cells (CTL cells) was higher in the HIV/HBV co-infected group, and Pre-S2 aa1-15 epitope was significantly higher (χ2=6.964, P=0.008). The incidence of deletions in PreS2 aa1-15 epitope in HIV/HBV co-infected group (11.1%) was higher than HBV mono-infected group (3.3%) (χ2=2.959, P=0.085). In the B cell epitopes, the incidence of mutations in Pre-S2 aa1-26 in the HIV/HBV co-infected group was significantly higher than HBV mono-infected group (χ2=6.924, P=0.010), and there was no statistical significance between two groups in other B cell epitopes. No differences in helper T cell (Th cell) epitopes were found between the two groups.@*Conclusions@#Co-infection with HIV increased the CTL cell epitopes’ mutations in the HBV Pre-S/S region, especially the 5′ end epitope mutations in Pre-S2 region, which indicated that HBV mutation is related to the host immune status, and showed guiding information for further study on the pathogenesis of HIV/HBV co-infection
ABSTRACT
Objective To investigate the genetic variations of gag-pol gene in human immunodeficiency virus-1(HIV-1) CRF07_BC strain in Guangdong Province.Methods From February to September in 2015,plasma samples of 78 cases with HIV 1 CRF07_BC infection in Guangdong were collected before antiretroviral treatment.Viral RNA was extracted from plasma.Gene (gag and pol) sequences were amplified by reverse transcriptase and nested-PCR using specific primers.Phylogenetic tree,genic dispersion rate,nucleotide polymorphism,selection pressure and variation characteristics were analyzed.Results The main transmission route of the enrolled patients was homosexual transmission (80.77％,63/78).The gag pol gene phylogenetic tree was divided into two sub-clusters.The strains from different transmission routes were not in cluster.The average genetic dispersion rate and average entropy of gag gene were both higher than those of pol gene.The average genetic dispersion and average entropy of p17 and p6 regions of gag gene were both higher than those of p24.The average genetic dispersion and average entropy of pol gene were higher than those of rt region.The average ds/dn values of gag and pol genes were greater than one.Compared with the common HIV-related antigenic epitopes (A2,A11,B39,B60,Cw1,Cw3,Cw8),the cytotoxic lymphocyte (CTL) epitope mutations in the P17 region were more in the consensus of GAG region than those in the P24 region.The epitope conserved rates were 26.92％,0,1.28％,0,96.15％,82.05％,84.62％ and 98.72％,respectively.The drug resistance rate of pol gene was 2.56％ (2/78).Conclusions The gag and pol genes of CRF07_BC strain in Guangdong are all mutated.Diversity of gag gene is greater than that of pol gene,and gag gene variation is mainly in p17 and p6 regions.gag and pol genes are both affected by negative selection pressure.P17 protein CTL epitope variability is greater than P24 protein epitope.The prevalence of drug resistance mutation is lower than the threshold.It's important to monitor the spread of drug-resistant strains.
ABSTRACT
Objective@#To investigate the combined effects of hepatitis B virus and hepatitis C virus (HBV/HCV) infection on the cause of death in patients with acquired immunodeficiency syndrome (AIDS).@*Methods@#The causes of death of 111 cases of AIDS with HBV/HCV (combined infection group) and 210 AIDS patients (single infection group) admitted to our hospital from 2012 to 2016 data were compared using chi-square test.@*Results@#There was no statistically significant difference in gender composition and age in the combined infection groups (P > 0.05). The main causes of death in the combined infection group were severe pneumonia (44.1%), end-stage liver disease (18.9%), and central nervous system infection (14.4%). The main causes of death in the single infection group were severe pneumonia (47.6%) and central nervous system infection (14.3%) and tumor (13.3%). There was no case of end-stage liver disease. The ratio of end-stage liver disease in the former group was significantly higher than that in the latter group (χ2 = 42.511, P < 0.001). The main cause of death in 12 HIV/HBV/HCV triple-infected patients was end-stage liver disease, accounting for 41.7%, which was significantly higher than 18.9% of end-stage liver disease in HIV/HBV or HIV/HCV dual infection (99 cases). And the difference was statistically significant (χ2 = 4.539, P = 0.033); however, the ratio of end-stage liver disease in 50 HIV/HBV co-infected patients and 49 HIV/HCV co-infected patients was 16.0% vs. 16.3%, respectively, and the difference was not statistically significant (χ2 = 0.002, P = 0.965). In the co-infected group, 36 patients had CD4+ cell counts >100/μl, the primary cause of death was end-stage liver disease, accounting for 38.2%. 75 patients with CD4+ ≤ 100/μl died due to end-stage liver disease, accounting for 9.3% and the difference was statistically significant (χ2 = 13.852, P < 0.05).@*Conclusion@#End-stage liver disease is the main cause of death in patients with AIDS combined with HBV or HCV, especially triplet infection and CD4+ cell count > 100/μl. An early diagnosis and treatment of HBV or HCV infection should commence as soon as possible.
ABSTRACT
Objective@#To investigate the optimal duration of pegylated-alpha interferon (Peg-INFα) combined with ribavirin (RBV) in treating chronic hepatitis C infection in human immunodeficiency virus (HIV)-infected patients.@*Methods@#A multicenter prospective study was conducted. The study subjects were divided into two groups; HIV/HCV co-infections (Group A, n = 158) and control with HCV-monoinfections (Group B, n = 60). All recruited patients received standard Peg-INFα plus RBV therapy. Group A was divided into 3 subgroups according to CD4+ cell counts: A1 subgroup, 79 cases, CD4+ counts > 350 cells /μl, who received anti-HCV before combination antiretroviral therapy(cART); A2 subgroup, 45 cases, CD4+ counts between 200 and 350 cells/μl, who did not start anti-HCV until they could tolerate cART well; A3 subgroup, 34 cases, CD4+ counts < 200 cells /μl, cART was administered first, and anti-HCV therapy was started when CD4+ counts > 200 cells/μl. The anti-HCV efficacy of two groups and 3 subgroups were compared. Statistical analysis for normal distribution and homogeneity of variance data was calculated by t-test and the counting data was analyzed by χ 2 test. The Mann-Whitney U test was used for non-normal data. A one-way analysis of variance (ANOVA) was used for the comparison of multiple groups, followed by SNK method. Multiple independent samples were used for non-parametric tests.@*Results@#There was no significant difference in age and baseline HCV RNA levels between groups and subgroups (P > 0.05). By an intent-to-treat (ITT) analysis, in Group A, the ratio of complete early virological response (cEVR) rate was 75.3% (119/158), the ratio of end of treatment virological response (eTVR) rate was 68.4% (108/158), and the ratio of sustained virological response (SVR) rate was 48.7% (77/158); in Group B, the ratio of cEVR rate was 93.3% (56/60), the ratio of eTVR rate was 90.0% (54/60), and the ratio of SVR rate was 71.7% (43/60); The therapeutic index of Group A were lower than those of Group B (P≤0.05). By per-protocol (PP) analysis, the ratio of cEVR rate in Group A [75.2% (88/112)] was still lower than that in Group B [93.3% (56/60)], but no significant differences were found in the ratio of eTVR rate and SVR rate between 2 groups (P > 0.05). Comparing the efficacy of subgroups (A1, A2 and A3) by ITT analysis, the ratios of cEVR rate were respectively 78.5% (62/79), 75.6% (34/45) and 67.6% (23/34); the ratios of eTVR rate were respectively 68.4%(54/79), 80.0%(36/45)and 52.9%(18/34); and the ratios of SVR rate were respectively 41.8%(33/79), 64.4%(29/45)and 44.1%(15/34). The ratio of eTVR in subgroup A2 was obviously higher than that in subgroup A3 and the ratio of SVR in subgroup A2 was statistically higher than that of subgroup A1(P≤0.05). However, by PP analysis, no significant differences of the therapeutic indexes were found among the respective subgroups (P > 0.05).@*Conclusion@#HIV-HCV co-infected patients would have better anti-HCV efficacy with Peg-INFα-2a plus RBV than HCV- monoinfected patients. The best time for initiating anti-HCV therapy in HIV-HCV co-infected patients is when CD4+ counts 200 cells/ μl.
ABSTRACT
Objective To explore the pathogen spectrum, drug resistance rate and clinical characteristics of pneumonia caused by non-tuberculous mycobacteria (NTM) in acquined immuno-deficiency syndrome (AIDS) patients.Methods The clinical data of 31 hospitalized AIDS patients with bronchoalceolar lavage flind (BALF) culture confirmed NTM pulmonary disease in Guangzhou No.8 People′s Hospital from January,2008 to February,2015 were retrospectively analyzed, including pathogen spectrum, drug resistance rate and clinical characteristics.The clinical characteristics and drug resistance were compared between Mycobacterium avmm-intracellulare complex (MAC) pneumonia and the non-MAC pneumonia, and t test and chi-square test were used.Results Of the 31 AIDS patients,28 were male and 3 were female, with the mean age of 40.9 years old.The 31 NTM strains were consisted of 14 MAC strains and 17 non-MAC strains (including 4 M.kansasii strains,3 M.lentiflavumstrains, 2 M.szulgai strains, 2 M.yongonense strains etc).There was no significant difference between two groups in sex ratio, mean age, clinical manifestations, laboratory tests and treatment outcome (all P>0.05).The major clinical manifestations included fever, productive cough, weight loss, anemia and low CD4+ count (<50/μL).Most patients showed thoracic lymphadenectasis and patchy shadows in lungs, and few patients had millet shadows and pericardial effusion.Compared with non-MAC strains, MAC strains had higher drug resistant rate of moxifloxacin (10/14 vs 4/17), levofloxacin (14/14 vs 8/17), and clarithromycin (11/14 vs 7/17).More extensively drug resistance strains were seen in non-MAC strains compared with MAC strains (11/14 vs 7/17).Conclusions MAC is the most common pathogen of NTM pulmonary disease in AIDS patients.The clinical features of pneumonia caused by MAC and non-MAC are similar, but drug resistance of MAC strains are more severe.
ABSTRACT
Objective To explore the diagnostic value of Talaromyces marneffei (T.marneffei)-specific mannose glycoprotein Mp1p antigen for T.marneffei infection in acquired immune deficiency syndrome (AIDS) patients.Methods All cases were recruited in this study from January 2012 to June 2015 in Guangzhou No.8 People′s Hospital, including 184 AIDS patients with T.marneffei infection confirmatively diagnosed by culture, and 205 controls including 176 AIDS patients without T.marneffei infection and 29 health controls.Double antibody sandwich enzyme linked immunosorbent assay and fluoroimmunoassay combined with double-antibody sandwich were both utilized to detect serum Mp1p antigen levels, and their sensitivity and specificity for diagnosing T.marneffei infection in patients with AIDS were analyzed.x2 test and t test were used for statistical analysis.Results The ratio of males to females and age of the study group were both comparable to those of the control group (x2=0.019, P=0.889;t=1.810,P=0.07, respecitvley).The sensitivities of double antibody sandwich enzyme linked immunosorbent assay and fluoroimmunoassay combined with double-antibody sandwich were 82.07%(151/184) and 83.15%(153/184), respectively (x2=0.076, P=0.783).The specificities were 93.17%(191/205) and 92.68%(190/205), respectively (x2=0.037, P=0.847).The accuracy values were 87.92%(342/389) and 88.17%(343/389), respectively (x2=0.012, P=0.912).The false positive rates were 6.83%(14/205) and 7.32%(15/205), respectively.The false negative rates were 17.93%(33/184) and 16.85%(31/184), respectively (x2=0.049, P=0.829).The positive predictive values were 91.52%(151/165) and 91.07%(153/168), respectively (x2=0.021, P=0.886).The negative predictive values were 85.27%(191/224) and 85.97%(190/221), respectively (x2=0.045, P=0.832).The Kappa values were 0.83 and 0.80, respectively.Conclusion Detection of serum Mp1p antigen of T.marneffei possesses high specificity and sensitivity, which may be utilized for rapid and early diagnosis of T.marneffei infection in patients with AIDS.
ABSTRACT
Objective To investigate the prevalence and characteristics of non-nucleoside reverse transcriptase inhibitors (NNRTIs)resistance-related gene mutations among the AIDS patients with virological suppression failure in Guangdong Province 2015.Methods Plasma samples from AIDS patients receiving highly active antiretroviral therapy for more than one year with viral loads > 1000 copies/mL from Guangdong province (except Shenzhen)were collected from January to December 2015.Total 612 HIV-1 gene fragments were amplified from plasma samples using self-developed lab method.Sub-genotypes were determined by phylogenetic tree according to the sequences,NNRTIs resistance-related mutations were determined in Stanford University HIV-1 Drug Resistance Database. The NNRTIs-resistance, the relationships of NNRTIs resistance-related mutations with baseline CD4 +T lymphocyte counts,transmission routes,antiviral regimens and HIV-1 genotypes were analyzed.SPSS 17.0 software was used to analyze the data.Results In 612 patients with virological suppression failure,the main NNRTIs resistance-related mutations were K103 (26.80%),Y181 (14.71 %),V179 (13.73%),G190 (11 .44%) and V106 (10.62%).The susceptibility rate of 310 patients (50.65%)to NNRTIs had changed,the highly resistant rate to nevirapine was 49.51 %,which was higher than that of efavirenz (43.14%),etravirine (5.56%) and rilpivirine (12.25%),respectively,and the differences were statistically significant (χ2 =5.00,296.3 and 198.0,all P 200 cells/μL was lower than that in those with baseline CD4 +T lymphocyte counts <200 cells/μL (χ2 =17.93,P <0.01 );the incidence rate of drug resistance was lower in intravenous drug abusers than that of sexually transmitted patients (χ2 =44.21 ,P <0.01 );while the incidence of drug resistance in patients receiving NVP-containing regimens was higher than that in those receiving EFV-containing regimens (χ2 =8.93,P <0.01 ),and the incidence rate was higher in patients with CRF01 _AE than that in those with CRF07_BC and CRF08 _BC (χ2 =8.46 and 8.47,P <0.01 ).Conclusions The results suggest that compliance education and follow-up should be strengthened in patients with high baseline CD4 +T lymphocyte counts and intravenous drug users,and patients with liver diseases should avoid using drugs containing NVP regimens.
ABSTRACT
Objective To detect the change of hepatitis C virus (HCV)RNA in the peripheral blood mononuclear cells (PBMC)and serum of patients with chronic hepatitis C (CHC)during treatment with peg-interferon α-2a (Peg IFNα-2a)plus ribavirin (RBV),and to analyze the clinical significance of HCV RNA detection in PBMC.Methods The peripheral blood samples of 20 CHC patients who visited Department of Infectious Diseases in Guangzhou No.8 People′s Hospital from June 2013 to December 2014,were collected during treatment with Peg IFNα-2a+RBV at different time points (week 0,2,4, 12,24,36 and 48).Serum and PBMC were separated.Accurate fluorescence quantification assay (Cobas TaqMan real time polymerase chain reaction[PCR])was used to detect HCV RNA level in serum,while real-time PCR and nest-PCR were applied to detect HCV RNA in PBMC.Categorical data were analyzed byχ2 test.Results Accurate fluorescence quantification of serum HCV RNA showed that HCV RNA level decline rapidly after treatment (F = 148.06,P < 0.01 ),and 18 patients achieved HCV RNA undetectable at week 12 of treatment.The positive rate of nest-PCR was higher than real-time PCR (all P <0.01).Comparison of HCV RNA levels in serum and PBMC from 20 cases found that,the clearance rate of HCV RNA in PBMC was postponed.Two patients whose HCV RNA in PBMC kept detectable relapsed at week 24 after end of treatment.Conclusions HCV RNA can be detected in PBMC of CHC patients and the positive rate of nest-PCR is higher than real-time PCR.Antiviral therapy is effective on HCV both inside and outside PBMC,but the clearance rate of HCV RNA in PBMC is postponed compared with that in serum.Slow clearance of HCV in PBMC may be a risk factor for relapse after end of treatment.
ABSTRACT
Objective To investigate the epidemiologic and clinical features of human immunodeficiency virus (HIV)/hepatitis B virus (HBV)co-infected patients.Methods Patients who confirmed with HIV infection and received highly active anti-retroviral therapy (HAART)at Guangzhou Eighth People′s Hospital were enrolled.HIV/HBV co-infected patients and HIV mono-infected patients were screened and their epidemiological and clinical features were analyzed before HAART.Comparison of the levels of alanine transaminase (ALT),aspartate transaminase (AST),CD4 + T lymphocyte and HIV RNA between the two groups were conducted.The data were statistically analyzed by chi-square test and nonparametric test.Results One hundred and sixty-five out of 1 218 (13.5 %)patients were hepatitis B surface antigen positive.The median ALT and AST levels of HIV mono-infected patients were 29 U/L and 34 U/L respectively,which were both higher than HIV/HBV co-infected patients (22 U/L and 25 U/L, respectively)(Z = - 4.270 and Z = - 5 .780,respectively,both P = 0.000 ).The median CD4 + T lymphocyte count of HIV/HBV co-infected patients was significantly lower than that of HIV mono-infected patients (Z = -2.980,P =0.003 ).The CD4 + T lymphocyte count was lower in hepatitis B e antigen (HBeAg)positive patients than HBeAg negative patients (Z =-2.660,P =0.008).The median CD4 + T lymphocyte count in patients with HBV DNA≥5 lg copy/mL was significantly lower than those with HBV DNA<5 lg copy/mL (Z = -2.311 ,P =0.021 ).The proportions of positive HBV DNA, HBV DNA≥5 lg copy/mL,abnormal ALT and AST in 54 patiens with CD4 + T lymphocyte counts <50/μL were 81 .5 %,66.7%,44.4% and 53.7%,respectively.All were significantly higher than patients with CD4 + T lymphocyte count≥50/μL(χ2 =6.159,P =0.046 ;χ2 =6.618,P =0.037 ;χ2 =7.144,P =0.028 andχ2 =9.586,P =0.008,respectively).Conclusions The prevalence of HBV/HIV co-infection is high in this study.The CD4 + T lymphocyte counts in HIV/HBV co-infected patients are lower,especially in patients with HBeAg positive and high HBV DNA level.The CD4 + T lymphocyte counts are associated with HBV DNA replication levels.
ABSTRACT
Objective To investigate the characteristics of mycobacteria species distribution in human immunodeficiency virus (HIV)-positive patients co-infected with mycobacteria in Guangzhou. Methods A total of 133 mycobacteria strains isolated from HIV-positive patients and 150 strains isolated from HIV-negative patients were included in this study. After DNA extraction of mycobacteria, mycobacteria species identification was performed by sequencing of multiple genes.Differences in the identified species were compared between patients with and without HIV infection and the correlation between CD4 + T cells level and the mycobacterial species distribution was analyzed.Chi-square test was used for statistical analysis.Results Of the 133 mycobacteria strains isolated from HIV-positive patients, 82 were identified as Mycobacterium tuberculosis complex (MTC ). Fifty-one were identified as nontuberculous mycobacteria (NTM),of which the main species was Mycobacterium avium complex (MAC,31/51).Of the 150 mycobacteria strains isolated from HIV-negative patients,126 were identified as MTC and 24 as NTM,of which the main species was Mycobacterium abscessus (9/24).In patients with CD4 + T cell counts ≤100/μL,the positive rate of mycobacteria was 75 .94%(101/133),93.55 %(29/31) of MAC and 85 .00%(17/20)of other NTM.When the CD4 + T cell counts >100/μL,the positive rate for mycobacteria were all obviously decreased.Conclusions The proportion of NTM infection is higher in HIV-positive patients than HIV-negative patients in Guangzhou. Among HIV-positive patients > the most prevalent NTM species is MAC, while Mycobacterium abscessus is the most common species in HIVnegative patients. Mycobacterial infection in acquired immunodeficiency syndrome patients is closely associated with low CD4+ cells level.
ABSTRACT
Objective To study the impact of HIV and hepatitis C virus ( HCV ) infection on peripheral expression of antiviral protein A3G and plasma IFN-αlevels.Methods Untreated patients with chronic hepatitis C(HCV infection group, n=43), AIDS(HIV infection group, CD4 +T0.05).There was no significant correlation between plasma IFN-αlevel and A3G mRNA expression (rs =0.04, P>0.05), and the levels of A3G mRNA and IFN-αshowed no correlation with HIV RNA and HCV RNA (all P>0.05).Conclusions A3G is highly expressed in PBMCs from HIV infected patients, and it may not be affected by the infection of HCV.A3G mRNA is not closely correlated with IFN-α, and it has not significant influence on HIV RNA and HCV RNA replication.
ABSTRACT
Objective To explore whether the mitochondrial toxicity markers of peripheral blood mononuclear cells (PBMC)are of significance in monitoring mitochondrial toxicity during highly active antiretroviral therapy (HAART)in patients with acquired immune deficiency syndrome (AIDS).Methods Mitochondrial DNA (mtDNA),mitochondrial thymidine kinase (TK2 )and p53-inducible ribonucleotide reductase small subunit 2 (p53R2 )were selected as mitochondrial toxicity markers.The expression changes of theses markers of PBMC in 22 AIDS patients were detected by real time quantitative polymerase chain reaction (q-PCR)at baseline,48 weeks and 96 weeks after initiation of the treatment. All the patients received stavudine/zidovudine and lamivudine as the mainstay of the HAART regimen. Independent-samples t test was used.Results The relative expression level of mtDNA in patients before HAART was 3.27 ± 0.94,and decreased to 2.16±0.85 at week 48 and 1 .66±0.66 at week 96, respectively.The differences were both significant compared with the level prior to the treatment (t =-3.90,P <0.01 and t =-6.29,P <0.01 ,respectively).The relative expression level of TK2 before HAART was 0.37 ±0.13,and increased to 1 .01 ±0.25 at week 48 and 2.13 ±0.61 at week 96 of the treatment.After pairwise comparisons of the three pairs of data (pre-HAART vs week 48 of the treatment,pre-HAART vs week 96 of the treatment and week 48 vs week 96 of the treatment),the differences were all significant (t = 10.77,8.00 and 3.56,respectively;all P < 0.01 ).The relative expression level of p53R2 was 0.86±0.39 before HAART,but gradually increased to 2.36 ±1 .14 and 7.73±0.65 ,respectively,at week 48 and week 96 of the treatment.The differences in p53R2 levels among three groups after pairwise comparison were all significant (t=3.27,12.26 and 13.25,respectively;all P < 0.01 ).Conclusions The expression levels of mtDNA,TK2 and p53R2 in PBMC could change significantly during HAART in AIDS patients,which might be used as indexes for monitoring mitochondrial toxicity.
ABSTRACT
Objective To investigate the prevalence and risk factors of highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (LD) in patients with acquired immunodeficiency syndrome (AIDS) treated with HAART in China.Methods A total of 137 AIDS patients treated with HAART for more than 2 years were analyzed.Sixteen clinical parameters (including gender,age,baseline body mass index,baseline human immunodeficiency virus [HIV] viral load,stage of disease,routes of HIV transmission,baseline CD4+ T lymphocyte count,white blood cell count,fasting plasma glucose level,serum triglycerides level,serum cholesterol level and other laboratory results,and HAART regimens) that might be associated with HAART-LD occurrence were evaluated using Cox proportional hazards models.Results HAART regimens were significantly correlated with HAART-LD (P=0.031),while the remaining 15 factors were not associated with the risk of HAART-LD (all P＞0.05).Patients who received stavudine d4T)-containing regimen was 2.684 times more likely to develop HAART-LD than patients who received zidovudine (AZT)-containing regimen (95 ％ CI:1.302-5.531,P=0.007) ; HAART-LD prevalence rates were gradually increased with treatment duration in both groups.First HAART-LD was seen at 24 weeks in both d4T group and AZT group,and the prevalence rates were 2.7％,1.6％ at 24 weeks,27.0％,7.9％ at 48 weeks and 37.8％,15.9％ at 96 weeks respectively.The prevalence of HAART-LD in d4T group was much higher than that in AZT group and the difference was statistically significant (x2 =8.285,P=0.004).Conclusions HAART regimen is an independent predictor of HAART-LD.HAART-LD tend to occur more frequently in patients treated with d4T or AZT,especially d4T.Our study recommends to avoid the use of d4T-contained HAART regimen.
ABSTRACT
Objective To study the mRNA expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) in the peripheral blood mononuclear cells (PBMC) in patients with chronic hepatitis C (CHC) and its regulation by exogenous interferon-α (IFN-α).Methods Twenty-eight CHC patients were recruited as case group and 14 healthy subjects were recruited as control group.APOBEC3G mRNA level (the ratio of APOBEC3G mRNA to housekeep geue 18s rRNA) in PBMC was determined by TaqMan real-time polymerase chain reaction (RTPCR).APOBEC3G mRNA levels were also dynamically measured in CHC patients treated with pegylated interferon (IFN)-α 2a at week 0,2,4,12,24,36 and 48 of treatment,and the plasma levels of IFN-α were simultaneously detected by enzyme-linked immunosorbent assay (ELISA).The data were analyzed by t test and analysis of variance using SPSS 11.0 software.Results The level of APOBEC3G mRNA in PBMC of CHC patients before treatment was 1.60× 10-4 ± 1.35 × 10-4,which was significantly lower than healthy controls 6.20 × 10-4 ±1.30 × 10-4 (t=3.147,P=0.003).The expressions of APOBEC3G mRNA were upregulated at week 12,24,36 and 48 of IFN treatment,which were 5.69×10-3±1.61×10-2,1.01×10-2±2.15×10-2,2.01×10-2±3.75×10-2 and 2.45× 10-2 ±4.08× 10-2,respectively,and all higher than that of pretreatment (F=3.46,5.67,10.27 and 25.65,respectively; P=0.042,0.030,0.010 and 0,respectively).IFN-α level in plasma were increased with treatment and reached the plateau at week 2 of the treatment until the end of observation.Conclusion Hepatitis C virus infection may be one of the reasons of APOBEC3G downregulation.
ABSTRACT
Objective To study the relationship between APOBEC3G mRNA level in peripheral blood mononuclear cells (PBMC) and serum hepatitis C viral RNA level in patients with chronic hepatitis C infection. Methods TaqMan real-time fluorescence relative quantitative polymerase chain reaction (RT-PCR) was used to quantify APOBEC3G mRNA levels in PBMC from 49 patients with chronic hepatitis C (CHC) and 31 healthy subjects. The relationship between APOBEC3G mRNA level and hepatitis C virus (HCV) viral load was analyzed. SPSS11. 0 statistics software was used for t test and regression analysis. Results APOBEC3G mRNA level in CHC patients [(1.5×10-5±1.9×10-5 ) copy/mL] was significantly lower than that [( 5. 2 × 10-5 ± 5. 5 × 10-5 ) copy/mL] in the healthy control subjects (t=-3.005, P＜0.01). While APOBEC3G mRNA level was not related with HCV viral loads (r=-0.082, P＞0.05). Conclusion HCV has an inhibitive effect on APOBEC3G expression, whereas APOBEC3G doesn't affect HCV replication directly in vivo.
ABSTRACT
Objective To compare the plasma hepatitis C virus(HCV)RNA levels detected by the fully automated viral load detection system(COBAS TaqMan)and the national real-time quantitative polymerase chain reaction(PCR)kit,and to investigate the clinical application value of these two methods in clinical practice.Methods A total of 168 serial plasma samples collected from 26 patients with chronic hepatitis C(CHC)before and at week 2,4,12,24,36 and 48 of antiviral treatment were detected by both COBAS Taqman 48 analyzing system and the national real-time quantitative PCR kit.The results of two methods were compared by chi square test and t test.Resnlts Both COBAS and national kit showed great positive detecting results when HCV RNA≥1×104IU/mL(at week O),and the virus load value detected by national kit was significantly higher than that detected by COBAS(t=2.05,P0.05).Conclusions The national TaqMan real-time quantitative PCR kits could be used to screen the suspected cases of HCV infecrion and to diagnose CHC cases with high HCV virus load.COBAS detection is more sensitive in cases with low HCV virus load and in on-treatment monitor during anti-HCV therapy.