Research progress in HIV non-occupational post-exposure prophylaxis among men who have sex with men in China / 中国热带医学

@#Abstract: In recent years, the HIV prevention intervention strategy has had a positive effect on reducing the HIV infection prevalence in China. HIV non-occupational post-exposure prophylaxis (nPEP) has become an effective measure to prevent HIV for men who have sex with men (MSM) exposed to possible risks. From the perspective of the "knowledge, attitude, and practice" theory, domestic and overseas scholars used outpatient data and questionnaires to investigate the awareness, attitude, usage, medication, follow-up, and drug prescription of HIV nPEP among MSM in China. This article reviewed the above-mentioned and found that the overall awareness rate of HIV nPEP among MSM in China is high with a positive attitude, but the actual utilization rate is very low. On a regional level, their follow-up after the medication is not ideal despite good medication. Drug prescription varies between different regions domestically. The prescription rate of tenofovir + emtricitabine + raltegravir is the highest, followed by the prescription rate of tenofovir + emtricitabine + dolutegravir, and tenofovir + lamivudine + dolutegravir. In the future, researchers should expand the number of study objects and the scope of the research sites in China, analyze the "knowledge, attitude, and practice" of HIV nPEP, medication follow-up, and medication prescription among MSM, and increase the research on HIV nPEP service areas to provide the reference for further formulating and refining the comprehensive HIV prevention intervention strategy among MSM in China.

Kinetic Characteristics of Neutralizing Antibody Responses Vary among Patients with COVID-19.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2. RESULTS: NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective. CONCLUSION: We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.

Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study.

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.

Assessing the association between platelets and immune recovery in HIV/HBV co-infected patients: A long-term cohort in Asia.

BACKGROUND: Previous studies have reported that platelet count is associated with the progression of liver disease caused by hepatitis B virus (HBV), but there have been no reports on whether platelet count is associated with immune recovery in HIV/HBV co-infected patients. METHODS: A retrospective analysis was conducted on 167 HIV-infected patients whose continuously highly active antiretroviral therapy (HAART) strategy was lamivudine +tenofovir+ efavirenz, of which 75 were HIV/HBV co-infected patients and 92 were HIV mono-infected patients. The biochemical examination results and demographic characteristics of all patients before HAART were collected, and routine blood test results (including platelet count) and immune cell count (including CD4 cells count) after all time points of HAART were obtained. All patients were observed until 72 months. CD4 cells count of 350 or 500 cells/µl 72 months after HAART served as the boundary for judging the immune reconstruction effect. RESULTS: The basic characteristics of HIV/HBV co-infected patients and HIV mono-infected patients were matched. All patients had a good viral response (HIV RNA <20 copies/ml, HBV DNA < 100 copies/mL) and immune response during HAART. The platelets with poor immune recovery in HIV/HBV co-infected patients were also maintained at an apparent lower level than that in patients with good immune recovery. However, this phenomenon was not found in HIV mono-infected patients. The platelet level at many time points after HAART therapy in HIV/HBV co-infected patients can predict the effect of immune recovery at 72 months after HAART. CONCLUSION: The platelet counts of HIV/HBV co-infected patients were correlated with CD4 counts during the follow-up of HAART. These results suggest that the mechanisms associated with thrombocytopenia may be involved in the regulation of immune recovery after treatment in HIV/HBV co-infected patients.

Antiretroviral Long-Term Efficacy and Resistance of Lopinavir/Ritonavir Plus Lamivudine in HIV-1-Infected Treatment-Naïve Patients (ALTERLL): 144-Week Results of a Randomized, Open-Label, Non-Inferiority Study From Guangdong, China.

Dual therapy with lopinavir/ritonavir (LPV/r) plus lamivudine (3TC) has been demonstrated to be non-inferior to the triple drug regimen including LPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) in 48-week studies. However, little is known about the long-term efficacy and drug resistance of this simplified strategy. A randomized, controlled, open-label, non-inferiority trial (ALTERLL) was conducted to assess the efficacy, drug resistance, and safety of dual therapy with LPV/r plus 3TC (DT group), compared with the first-line triple-therapy regimen containing tenofovir (TDF), 3TC plus efavirenz (EFV) (TT group) in antiretroviral therapy (ART)-naïve HIV-1-infected adults in Guangdong, China. The primary endpoint was the proportion of patients with plasma HIV-1 RNA < 50 copies/ml at week 144. Between March 1 and December 31, 2015, a total of 196 patients (from 274 patients screened) were included and randomly assigned to either the DT group (n = 99) or the TT group (n = 97). In the primary intention-to-treat (ITT) analysis at week 144, 95 patients (96%) in the DT group and 93 patients (95.9%) in the TT group achieved virological inhibition with plasma HIV-1 RNA <50 copies/ml (difference: 0.1%; 95% CI, -4.6-4.7%), meeting the criteria for non-inferiority. The DT group did not show significant differences in the mean increase in CD4+ cell count (247.0 vs. 204.5 cells/mm3; p = 0.074) or the CD4/CD8 ratio (0.47 vs. 0.49; p = 0.947) from baseline, or the inflammatory biomarker levels through week 144 compared with the TT group. For the subgroup analysis, baseline high viremia (HIV-1 RNA > 100,000 copies/ml) and genotype BC did not affect the primary endpoint or the mean increase in CD4+ cell count or CD4/CD8 ratio from baseline at week 144. However, in patients with genotype AE, the DT group showed a higher mean increase in CD4+ cell count from baseline through 144 weeks than the TT group (308.7 vs. 209.4 cells/mm3; p = 0.038). No secondary HIV resistance was observed in either group. Moreover, no severe adverse event (SAE) or death was observed in any group. Nonetheless, more patients in the TT group (6.1%) discontinued the assigned regimen than those in the DT group (1%) due to adverse events. Dual therapy with LPV/r plus 3TC manifests long-term non-inferior therapeutic efficacy, low drug resistance, good safety, and tolerability compared with the first-line triple-therapy regimen in Guangdong, China, indicating dual therapy is a viable alternative in resource-limited areas. Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR1900024611].

The clinical significance of myeloid-derived suppressor cells in dengue fever patients.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play immunosuppressive roles in cancers and some infectious diseases; however, their role in dengue fever (DF) remains unknown. This study evaluated the clinical significance of MDSCs in DF patients. METHODS: This study comprised 178 non-severe DF patients, 20 non-dengue fever (NDF) controls, and 30 healthy donors. The DF patients were divided into the following five groups based on the fever duration from its onset to the day of sample collection: fever duration of 1-2, 3-4, 5-6, 7-8, and > 9 days. Among these DF patients, 14 were monitored for eight days, and their peripheral blood samples were collected every two days. The mononuclear cells were isolated and analyzed using flow cytometry. The correlation between the MDSCs and clinical and immunological indicators of the DF patients was evaluated using Spearman analysis. RESULTS: The count of the peripheral blood MDSCs, especially monocytic MDSCs, of the 178 DF patients were dramatically higher than those of the NDF and healthy controls, and remarkably decreased with the fever duration. Moreover, the MDSC count correlated with some indicators, including the dengue viral load (rho = 0.367, p < .001), body temperature (rho = 0.263, p = .005), prothrombin time (rho = 0.475, p < .001), CD4+ T cell number (rho = - 0.317, p < .001), CD8+ T cell number (rho = - 0.361, p < .001), "programmed cell death protein 1" (PD-1) (rho = - 0.347, p < .001), "T cell immunoglobulin domain and mucin domain-3" (Tim3) (rho = - 0.258, p = .001), interferon-α (IFN-α) (rho = 0.43, p < .001), and "regulated upon activation normal T-cell expressed and secreted" (RANTES) (rho = 0.278, p = .019). Furthermore, the level of arginase-1, but not nitric oxide, was higher in the DF patients than in the healthy controls and was closely related to the number of MDSCs (rho = 0.265, p = .024). CONCLUSIONS: Our study reveals a significant correlation between MDSCs and DF clinical indicators, posing MDSCs as potential target cells for DF treatment.

ICAM-1 controls development and function of ILC2.

Group 2 innate lymphoid cells (ILC2s) are emerging as key players in the pathogenesis of allergic airway inflammation. The mechanisms regulating ILC2, however, are not fully understood. Here, we found that ICAM-1 is required for the development and function of ILC2. ICAM-1-deficient (ICAM-1-/- ) mice displayed significantly lower levels of ILC2s in the bone marrow and peripheral tissues than wild-type controls. CLP transfer and in vitro culture assays revealed that the regulation of ILC2 by ICAM-1 is cell intrinsic. Furthermore, ILC2s from ICAM-1-/- mice were functionally impaired, as indicated by the diminished production of type-2 cytokines in response to IL-33 challenge. The reduction in lung ILC2s caused a clear remission of airway inflammation in ICAM-1-/- mice after administration of papain or Alternaria alternata. We further demonstrate that ILC2 defects caused by ICAM-1 deficiency are due to ERK signaling-dependent down-regulation of GATA3 protein. Collectively, these observations identify ICAM-1 as a novel regulator of ILC2.

Epidemiological and Virological Characterizations of the 2014 Dengue Outbreak in Guangzhou, China.

Dengue used to be recognized as an imported and sporadic disease in China. Since June 2014, an unexpected large dengue outbreak has attacked Guangzhou, China, resulting in more than 40,000 cases. Among the 1,942 laboratory-confirmed hospitalized dengue cases, 121 were diagnosed as severe dengue according to the 2009 WHO guideline, and 2 patients finally died. Laboratory diagnosis and virus isolation demonstrated that the majority (96%) cases were caused by dengue virus serotype 1 (DENV-1), and the others by serotype 2 (DENV-2). 14 DENV strains were isolated from the sera of acute-phase dengue patients during this outbreak, and the complete envelope (E) gene of 12 DENV-1 strains and two DENV-2 strains were determined using RT-PCR assay. Phylogenetic analysis based on the E gene revealed the DENV-1 strains isolated during the outbreak belonged to genotype I and V, respectively. These isolates formed three clades. DENV-2 isolates were assigned to the same clade belonging to genotype cosmopolitan. These strains isolated in 2014 were closely related to the isolates obtained from the same province, Guangdong, in 2013. No amino acid mutations known to increase virulence were identified throughout the E protein of isolates in 2014. These results indicate that dengue is turning into endemic in Guangdong, China, and extensive seroepidemiological investigation and mosquito control measures are critically needed in the future.

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: This combination ART regimen is safe and effective for patients with HIV/HBV co-infection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01751555; https://clinicaltrials.gov/ct2/show/NCT01751555.

Hepatitis C therapy with interferon-α and ribavirin reduces the CD4 cell count and the total, 2LTR circular and integrated HIV-1 DNA in HIV/HCV co-infected patients.

This study investigated whether treatment with IFN-α and ribavirin (RBV) reduces 2LTR circular HIV DNA in addition to the total and integrated HIV DNA. Two groups of patients were enrolled. Group 1 comprised HIV/HCV co-infected patients who were treated with highly active antiretroviral therapy (HAART), IFN-α and RBV for 48 weeks. After the 48 weeks of treatment, IFN-α and RBV treatment was discontinued and HAART was continued. Group 2 comprised HIV-infected patients who were treated with HAART. Real-time polymerase chain reaction (RT-PCR) was used to quantify the levels of HIV-1 DNA. We found that compared with Group 2 patients, Group 1 patients exhibited an obvious decrease in the CD4 cell count and the total DNA, 2LTR circular DNA, and integrated HIV DNA after 48 weeks of treatment. After the discontinuation of IFN-α and RBV treatment in Group 1 patients, the levels of HIV DNA recovered. Therefore, we concluded that treatment with IFN-α and ribavirin (RBV) reduces 2LTR circular HIV DNA.

HIV, hepatitis B virus, and hepatitis C virus co-infection in patients in the China National Free Antiretroviral Treatment Program, 2010-12: a retrospective observational cohort study.

BACKGROUND: Hepatitis-related liver diseases are a leading cause of mortality and morbidity among people with HIV/AIDS taking combination antiretroviral therapy. We assessed the effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection on HIV outcomes in patients in China. METHODS: We did a nationwide retrospective observational cohort study with data from the China National Free Antiretroviral Treatment Program from 2010-11. Patients older than 18 years starting standard antiretroviral therapy for HIV who had tested positive for HBV and HCV were followed up to Dec 31, 2012. We used Kaplan-Meier analysis and Cox proportional hazard models to evaluate survival, and logistic regression models to estimate virological failure, immunological response, and retention in care. FINDINGS: 33 861 patients with HIV met eligibility criteria. 2958 (8·7%) participants had HBV co-infection, 6149 (18·2%) had HCV co-infection, and 1114 (3·3%) had triple infection. All-cause mortality was higher in participants with triple infection (adjusted hazard ratio 1·90, 95% CI 1·53-2·37) and HCV co-infection (1·46, 1·25-1·70) than in those with HIV only, but not in those with HBV co-infection (1·06, 0·89-1·26). People with triple infection were also more likely to have virological failure (adjusted odds ratio [OR] 1·26, 95% CI 1·02-1·56) than were those with HIV only, whereas the difference was not significant for those with HBV co-infection (0·93, 0·80-1·10) or HCV co-infection (1·10, 0·97-1·26). No co-infection was significantly associated with a difference in CD4 cell count after 1 year of treatment. Loss to follow-up was more common among participants with triple infection (OR 1·37, 95% CI 1·16-1·62) and HCV co-infection (1·30, 1·17-1·45), but not HBV co-infection (0·93, 0·82-1·05), than among those with HIV only. INTERPRETATION: Screening for viral hepatitis is important in individuals diagnosed as HIV positive. Effective management for viral hepatitis should be integrated into HIV treatment programmes. Long-term data are needed about the effect of hepatitis co-infection on HIV disease progression. FUNDING: The National Center for AIDS/STD Control and Prevention, China Center for Disease Control and Prevention.

[Differential response to pegylated interferon plus ribavirin combination therapy in chronic hepatitis C and HIV/HCV co-infected patients].

OBJECTIVE: To investigate the potential differences in response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) combination therapy in patients with hepatitis C virus (HCV) mono-infection and human immunodeficiency virus (HIV)/HCV co-infection. METHODS: Seventy HIV/HCV patients and sixty HCV patients, were administered a 48-week course of Peg-IFN + RBV. The HCV load was tested by the COBAS automatic viral load analysis system (lower limit of quantification = 15 IU/ml) at treatment weeks 0 (baseline), 4, 12, 24, and 48 and at week 24 after drug withdrawal. The patients were also genotyped by sequencing for the host-encoded interleukin (IL)-28B single nucleotide polymorphisms (SNPs) related to HCV Peg-IFN + RBV therapy outcome: rs8099917, rs12979860 and rs12980275. In addition, the HCV-encoded NS5B gene region was genotyped by nested-PCR and sequencing followed by BLAST searching of the Los Alamos National Laboratory HCV database. The significance of between-group differences in response to therapy and roles of SNPs were evaluated by statistical analyses. RESULTS: The ratio of sustained virological response (SVR) was significantly lower in the HIV/HCV co-infected patients than the HCV mono-infected patients (32.9% vs. 71.7%; P less than 0.001). While the HIV/HCV co-infected patients did not show a significant difference in SVR ratio achieved between individuals infected with the HCV-1 genotype and the non-HCV-1 genotype (30.8% vs. 33.3%; P = 1.000), the HCV mono-infected patients did (86.1% vs. non 50.0%, P = 0.002). Moreover, the SVR ratio was higher in the HCV-1 genotype HCV mono-infected patients than in the HIV/HCV-1 genotype co-infected patents (30.8% vs. 86.1%; P less than 0.001). The different IL-28B genotypes were not significantly correlated to the PEG-IFN+RBV therapy response of either HCV mono-infected patients or HIV/HCV co-infected patients (P more than 0.05). CONCLUSION: HCV mono-infected patients respond better to Peg-IFN + RBV therapy than HIV/HCV co-infected patients. The HCV-1 genotype may promote this therapy response in HCV mono-infected patients, but the IL-28B genotypes appear to play no significant role.

[Analysis of death causes of 345 cases with HIV/AIDS in Guangdong area].

OBJECTIVE: To analyze the death causes of 345 cases with HIV/AIDS in Guangdong area. METHODS: The situations of 345 hospitalized death cases with HIV/AIDS were conducted by retrospective analysis. RESULTS: (1)There were total 3406 hospitalized cases with HIV/AIDS in a hospital from January 2001 to December 2011 and 345 cases died, the fatality rate was 10. 13%. Since 2005 the introduction of free anti-viral treatment, the fatality rate of HIV/AIDS declined. The fatality rate of the patients whose CD4+ T lymphocyte counts <200 cells/microl was 14.61% (299/2046) and it was significantly higher than that of patients whose CD4 T lymphocyte counts >or=200 cells/microl (P <0.01). (2) 99.42% of the death cases had more than one kind of opportunistic infections (OI) and there were 924 cases of OI totally. 84. 64% of OI related to the death directly. Fungal infection was the most common in OI, followed by bacterial infection. Most OI occurred in the lungs, mouth, other systemic disseminated diseases, gastrointestine, central nerver system, septicemia, skin. The AIDS defining opportunistic infections such as several pneumonia, disseminated penicilliosis marneffei and CNS infections accounted for 29.65%. Other factors that caused HIV/AIDS death included opportunistic tumors, HIV related disease and non AIDS-related disease accounted for 15.36%. No accepted effective highly active antiretroviral therapy (HARRT) also constituted factors of death. Among cases which accepted HARRT treatment, only 6.96% had the period of treatment over three months. CONCLUSION: The fatality rate of end-stage AIDS patients was high and the opportunistic infections was the most important cause of death. Early diagnosis and treatment for opportunistic infections, timely effective HARRT were the key to improve the quality of life of AIDS patients.

Genotyping of Pneumocystis jirovecii isolates from Chinese HIV-infected patients based on nucleotide sequence variations in the internal transcribed spacer regions of rRNA genes.

Genetic diversity of Pneumocystis jirovecii isolates based on internal transcribed spacer (ITS) of the nuclear rRNA locus has previously been reported. The information about ITS genotype and epidemiology of this organism in Chinese human immunodeficiency virus-infected patients has not been available. In this study, 12 bronchoalveolar lavage fluid specimens obtained from HIV-infected patients were analyzed by PCR followed by cloning, sequencing and typing. Three ITS1 genotypes (E, B and 'H') and four ITS2 genotypes (b, g, i and r) as previously reported were identified, the most common of which were E, b and i. Five ITS haplotypes (Eg, Eb, Bi, Er and 'H'r) and 19 new combination types were also identified with the most common types being Eg (four of 12 patients, 10 of 60 clones), Eb (three of 12 patients, 11 of 60 clones) and Bi (three of 12 patients, 10 of 60 clones). Nine patients were found to be co-infected with more than one ITS genotype of P. jirovecii. The prevalence of ITS genotypes in HIV patients from one Chinese hospital did not seem to be significantly different when compared to reports from other countries.

Genetic diversity analysis of Penicillium marneffei isolated from AIDS patients in Guangdong, China using randomly amplified polymorphic DNA.

BACKGROUND: Penicillium marneffei (P. marneffei) is an emerging pathogenic fungus that can cause invasive mycosis in patients with AIDS. The epidemiological features of P. marneffei infection in AIDS patients in Guangdong province remain unclear so far. This study aimed to investigate the genetic diversity within a population of 163 P. marneffei isolates obtained from AIDS patients and search for the dominant clinical strains in Guangdong province. METHODS: One hundred and sixty-three P. marneffei isolates obtained from AIDS patients in Guangdong province during January 2004 and December 2009 were studied by randomly amplified polymorphic DNA (RAPD) using two random primers (H2 and H22). The degree of similarity between samples was calculated through similarity coefficients from RAPD fragment data and the dendrogram was assessed using the unweighted pair group method with arithmetic mean (UPGMA). RESULTS: Two primers showed a high degree of discrimination and good stability. Primer H2 yielded eight different patterns (H2-1 to H2-8) among 163 isolates with the discriminatory power being 0.413. Primer H22 identified seven types (H22-1 to H22-7) among 163 isolates with the discriminatory power being 0.467. Genetic similarity coefficients based on RAPD data among 163 P. marneffei isolates ranged from 0.681 to 0.957, 61.96% of which were no less than 0.83. The discriminatory power of the two primers was 0.524. One hundred and sixty-three P. marneffei isolates were clustered into nine distinct groups (groups I to IX) at the similarity coefficient value of 0.83 and group I was the most common, including 101 strains (61.96%). CONCLUSION: The RAPD analyses could provide important information as to the degree of genetic diversity and the relationship among clinical P. marneffei isolates, revealing genetic polymorphism and dominant strains.

[Epidemiologic and therapeutic status study of patients with hepatitis C].

OBJECTIVE: To investigate the different infective mode, the time from be infectived to be diagnosed and the time from be diagnosed to be treated of patients with hepatitis C. METHODS: The different infective mode, the time from be infectived to be diagnosed and the time from be diagnosed to be treated of 216 patients with hepatitis C from march 2004 to march 2009 were retrospectively analyzed. RESULTS: 72.22 percents patients suffered from post transfusion hepatitis C (PTHC) and 27.78 percents patients suffered from sporadic hepatitisC (SHC). 32.61 percents patients were diagnosed after be infectived 15-20 years later. 3.26 percents patients were diagnosed after be infectived more than 20 years later. 33.80 percents patients were treated after be diagnosed more than 5 years later. 17.13 percents patients were treated after be diagnosed 10-15 years later. CONCLUSION: Most patients were infectived with hepatitis C by transfusing blood or blood products. Most patients were diagnosed after be infectived more than 15 years later. Almost half of patients were treated after be diagnosed more than 5 years later, and a significant portion of percents patients were treated after be diagnosed more than 10 years later.

[The therapeutic effects of highly active anti-retroviral therapy in 74 treatment-naive patients with AIDS in China].

OBJECTIVE: To evaluate the therapeutic effect of highly active anti-retroviral therapy (HAART) in treatment-naïve Chinese patients with AIDS, to provide evidences for standardizing HAART. METHODS: Seventy-four treatment-naive AIDS patients were initiated with HAART and followed up regularly for 3 years. The clinical and laboratory data, side effects and drug resistance were observed and analyzed during the follow-up period. RESULTS: Of the 74 patients, 46 were males and 28 were females, with the average age being 42 years. The mean HIV viral load was (2.2 ± 2.0) × 10(5) copies/ml and the baseline mean CD(4)(+)T lymphocyte count was (62 ± 71) cells/µl before treatment. After treatment for 3, 6, 12, 18, 24, 30 and 36 months, the percentage of undetectable HIV viral road (less than 50 copies/ml) was 71.6%, 83.8%, 75.7%, 77.0%, 82.4%, 81.1% and 79.7% respectively, and CD(4)(+)T lymphocyte count ascended to (167 ± 105), (177 ± 129), (238 ± 137), (290 ± 158), (304 ± 191), (331 ± 175) and (352 ± 202) cells/µl. The increase in amplitude of CD(4)(+)T lymphocyte count in different periods examined was different, with the period of 0-3 months post-treatment demonstrating the most obvious augmentation (P < 0.01). The most common adverse reactions were liver function injury (52/74, 70.3%), hyperlipemia (52/74, 70.3%), hematopoietic inhibition of the bone marrow (33/74, 44.6%), peripheral neuritis (32/74, 43.2%) and lipoatrophy (26/74, 35.1%). Clinical drug resistance were found in nine patients and HIV gene mutations were detected in these patients. CONCLUSIONS: Chinese treatment-naive AIDS patients have achieved good virological and immunological response to generic-drug-predominant HAART regimes with low drug resistance, but relatively more side effects.

[Analysis of hepatitis C virus (HCV) subtypes in HIV/HCV co-infected and HCV mono-infected individuals in Guangdong province].

OBJECTIVE: To explore the transmission routes, genotypes/subtypes distribution and genetic character of HCV in HIV/HCV co-infected and HCV mono-infected individuals in Guangdong Province. METHODS: Reverse transcription (RT) nested PCR was performed to amplify the HCV NS5B gene region from 95 HIV/HCV co-infected and 99 HCV mono-infected individuals lived in Guangdong province. The PCR products were then sequenced for HCV subtyping. Genetic analysis was done by MEGA4 software. RESULTS: (1) HIV/HCV co-infected individuals infected HCV mostly through injection drug use (IDU, 78.9%), the HCV subtypes were identified as 6a (53.7%), 3a (17.9%), 1b (15.8%), 3b (11.6%) and 1a (1.0%) respectively, the genetic distance within subtype 1b was longer than those within other subtypes, the predominant HCV subtype in HIV/HCV co-infected individuals infected through IDU was 6a (60.0%). (2) HCV mono-infected individuals infected HCV mostly through blood or blood products transfusions (80.8%), the HCV subtypes were identified as 1b (67.7%), 6a (17.2%), 3a (6.1%), 2a (5.0%), 3b (2.0%), 4a (1.0%) and 5a (1.0%) respectively, the genetic distance within subtype 1b was also longer than those within other subtypes, the predominant HCV subtype in HCV mono-infected individuals infected through blood or blood products transfusions was 1b (76.2%). CONCLUSION: The diversity of HCV subtypes in HIV/HCV co-infected and HCV mono-infected individuals in Guangdong Province was high, both the major transmission route and HCV subtype between HIV/HCV co-infected individuals and HCV mono-infected individuals were different.