Objective To evaluate the immune reconstitution of HIV-1 infected individuals after long-term highly antiretroviral therapy (HAART). Methods Twenty-five HIV-1 infected individuals receiving HAART, 17 without HAART and 15 healthy controls were included in the study. CD4 +T, CD8 +T,CD8/human leukocyte antigen DR (HLADR) + T, CD8/CD38 +T cells, and the expression of CD127 on CD3 +T cells from peripheral blood samples were measured by flow cytometry. IL-7 in peripheral blood was measured by enzyme-linked immunosorbort assay (ELISA) in HAART group. t test was performed to compare the measurement data among the groups. Results Before HAART, the count of CD4 + T cells in HIV-1 infected group was lower than that of the healthy control (t =9. 12, P ＜0. 01 ), while the counts of CD8 + T,CD8/HLADR+T, and CD8/CD38 +T cells were higher than those of the healthy control (t = 4.48, 4.89 and 3.88, P＜0. 01 ). Ater 7 years' antiviral therapy, CD4 +T cells increased, CD8 +T cells decreased, but both of them didn' t reach to the normal levels ( t = 2.66 and 2.43, P ＜ 0.05 ). While the counts of CD8/HLADR+T cells and CD8/CD38 +T cells almost reached to the normal levels (t = 0. 86 and 1.39, P ＞0.05). Before HAART, the concentration of IL-7 in HIV-1 infected group was higher than that in healthy controls (t =5.31, P ＜0.01 ). It decreased with HAART, but was still higher than the normal level (t =2. 81, P ＜ 0. 05 ). The expression of CD127 on CD3 + CD8 + T cells in non-HAART group was significantly lower than that in healthy control ( t =- 6.01, P ＜ 0.01 ), while that in HAART group was higher ( t = 2.32,P ＜0.05), but still not reached to the normal level ( t = 4.49, P ＜ 0. 05 ). CD127 expression on ( CD45RA + ) CD3 + CD8 + T cells almost increased to the normal level ( t= 0. 28, P ＞ 0. 05 ), while that on ( CD45RO + ) CD3 + CD8 + T cells was still remarkably lower than the normal ( t = 4. 86, P ＜ 0. 05 ). Conclusion Long-term HAART can partially restore the count and function of lymphocyte subsets in HIV-1 infected individuals, and the abnormal immune activation can be inhibited.

OBJECTIVETo further study the resistance of HBV to high activity antiretrovirus therapy(HAART).

METHODSHBV-DNA was quantitatively detected by real-time PCR in 36 HIV/HBV superinfection subjects, C region and P region HBV-DNA in high copies HBV-DNA subjects were detected by routine PCR, PCR products were purified and sequenced and compared with the HBV international Genbank using BLSAT softy ware.

RESULTHBV-DNA was positive in 4 of 36 patients (11.1%) and another 3 had low copies(<10(4)copies/ml), one had a high HBV-DNA copies (10(7)copies/ml). It's HBV-DNA C region sequence had mutation on 2 sites (nt 2412 T/C; nt 2413 T/C) and 1 mutation P region (nt 741 A/G, also YMDD/YVDD) compared with HBV international Genbak reference sequence.

CONCLUSIONThe HBV resistance to HAART may be related with multiple genetic mutations in the C and P regain of HBV-DNA.

Antiretroviral Therapy, Highly Active ; Base Sequence ; DNA, Viral ; chemistry ; Drug Resistance, Viral ; HIV Infections ; drug therapy ; virology ; Hepatitis B ; drug therapy ; virology ; Hepatitis B virus ; genetics ; Humans ; Mutation

OBJECTIVETo find out the mechanism of drug resistance by detecting the mutations of HIV RNA in patients who failed in the anti-HIV therapy, to direct the clinical use of anti-HIV drugs and to complement the existing drug resistant database.

METHODSHIV RNA and DNA were extracted from the plasma of 10 HIV-infected patients who developed drug resistance in the Clinic of AIDS, Ruhr University, Bochum, Germany. Then HIV-RNA was amplified in the reverse transcriptase (RT) and protease regions by polymerase chain reaction (PCR). After purified, the PCR products was sequenced. The acquired sequences were compared with the international standard strain HXB2CG and the resistant database of Stanford University.

RESULTSSome mutations were found to cause the corresponding resistance to certain drugs and were consistent with the clinical results. Some mutations existed in some patients, such as V179I in RT and K20T, K20I in protease, which hadn't been reported in the resistant database of Stanford University yet.

CONCLUSIONPatients who fail in HAART have different mutations in RT and protease regions. Mutations such as V179I in RT and K20T, K20I etc in protease may be related to drug resistance.

Adult ; Antiretroviral Therapy, Highly Active ; Drug Resistance, Viral ; HIV Infections ; drug therapy ; virology ; Humans ; RNA, Viral ; blood ; Treatment Failure

OBJECTIVETo study the pathogenesis role of immune system activation in AIDS related Kaposi's sarcoma(AIDS-KS).

METHODSThe serum levels of sFas, beta 2-microglobin, IL-10, IL-16, IL-18, IL-6 and sIL-4R were detected by ELISA in 8 AIDS-KS patients, 28 patients with HIV infection but without Kaposi's sarcoma(HIV-NKS) and 16 normal controls. The lymphocyte and their subsets, CD38(+) CD8, HLA-DR(+)CD8 in the peripheral blood mononuclear cell (PBMCs) in 12 AIDS-KS and 32 HIV-NKS were detected by flow cytometer.

RESULTSBeta 2-MG and sIL-4R in HIV-NKS were significantly higher than those in normal controls(P<0.05), IL-16 in HIV-NKS was significantly lower than that in controls(P<0.05). IL-18 was higher in both AIDS-KS and HIV-NKS compared with normal controls. In AIDS-KS, CD3, CD4, CD8, NK and HLA-DR(+)CD8 were lower than those in HIV-NKS whereas CD19 and CD38(+)CD8 were higher than those in HIV-NKS. But the difference was not statistically(P<0.05).

CONCLUSIONAlthough both AIDS-KS and HIV-NKS demonstrate some activation of immune system, there appears to be no significant difference between immune responses in KS and NKS patients. These data suggest that the activation of the immune system is unlikely to contribute significantly to the pathogenesis of AIDS-KS.

Acquired Immunodeficiency Syndrome ; complications ; immunology ; Cytokines ; blood ; HLA-DR Antigens ; blood ; Humans ; Interleukin-16 ; blood ; Sarcoma, Kaposi ; etiology ; immunology

OBJECTIVETo measure CCR5 and CXCR4 chemokine receptor expression on CD4 and CD8 T cells in HIV-1 infection and to relate levels to the distribution of CD45RO memory and CD45RA-naive subsets after effective HAART.

METHODSFour-color cytofluorometry with appropriate conjugated monoclonal antibodies (mAbs) was performed to define CD45RA and CD45RO subsets of CD4 and CD8 T cells and measure the expression of CCR5, CXCR4 in blood from 43 received HAART patients and 5 non-treated HIV and 13 healthy controls.

RESULTSThe levels of CCR5 and CXCR4 on CD4 and CD8 T cells and their CD45RO/CD45RA subsets in HIV-1-infected patients had not any statistical significance than that on control subjects and effective HAART could adjust the expression on T cells.

CONCLUSIONCXCR4/CCR5 plays an important role in the progress of HIV-1 infection. The most favorable condition for treatment should be initiated before stage B.

Acquired Immunodeficiency Syndrome ; drug therapy ; immunology ; Antiretroviral Therapy, Highly Active ; CD4-Positive T-Lymphocytes ; chemistry ; CD8-Positive T-Lymphocytes ; chemistry ; HIV-1 ; Humans ; Receptors, CCR5 ; blood ; drug effects ; Receptors, CXCR4 ; blood ; drug effects

OBJECTIVETo study the significance of cytokines in patients with HIV and hepatitis viruses co-infection.

METHODSSerum levels of IL-18 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). HIV-RNA levels were measured in EDTA plasma by quantitative reverse polymerase chain reaction (PCR). CD4(+) lymphocyte counts were determined by four-color Flow cytometry (FCM).

RESULTSThe levels of IL-18 were significantly higher in HIV-infected persons compared with those in controls (P<0.05). With HIV disease progression, IL-18 levels increased while Il-10 levels decreased. HCV patients showed lower levels of IL-18 and IL-10 than those of the co-infection group.

CONCLUSIONUnivariate analyses shows significant co-variables IL-10 in co-infection. Up-regulating IL-18 activity and/or down-regulating IL-10 may be a potential therapy to patients with HIV and hepatitis viruses co-infection.

Acquired Immunodeficiency Syndrome ; complications ; immunology ; Adult ; Female ; HIV-1 ; Hepatitis B ; complications ; immunology ; Hepatitis C ; complications ; immunology ; Humans ; Interleukin-10 ; blood ; Interleukin-18 ; blood ; Male ; Middle Aged ; T-Lymphocytes, Cytotoxic ; immunology ; Th1 Cells ; immunology ; Th2 Cells ; immunology

OBJECTIVETo study the pathogenic role of Fas/CD95 in HIV-1 infection subjects, and to investigate the effects of HIV on plasma levels of sFas and the expression of CD95 on different CD4(+) T lymphocyte subpopulations.

METHODSFour-color flow cytometry was used to determine the expression of CD95, CD45RO, CD45RA on CD4(+ )T lymphocyte in peripheral blood from HIV-1 infection subjects and serum Fas levels were quantified by enzyme-linked immunosorbent assay (ELISA).

RESULTCompared with healthy controls, serum Fas levels were significantly increased (P<0.05) in HIV group and positively correlated with the disease progress. The expression of CD95 on naive T-lymphocyte subsets was increased whereas that on memory T-lymphocyte subsets was decreased.

CONCLUSIONFas plays an important role in the deletion of CD4(+) T-lymphocyte during HIV-1 infection. Further understanding of the relationship between Fas/CD95 and CD45RO/CD45RA may help to predict the progression of the disease and the clinical outcome.

Acquired Immunodeficiency Syndrome ; immunology ; Adult ; Apoptosis ; CD4-Positive T-Lymphocytes ; pathology ; Female ; HIV-1 ; Humans ; Leukocyte Common Antigens ; blood ; Male ; Middle Aged ; fas Receptor ; blood ; physiology

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 study the effect of highly active antiretroviral therapy (HAART) on plasma levels of MSP and MCP-1 in AIDS patients.

METHODSForty Chinese AIDS patients were treated with HAART for 3 months and 84 German AIDS patients with HAART for 3 to 6 years. The pre-treatment and post-treatment plasma levels of MSP and MCP-1 were measured by enzyme-linked immunosorbent assay (ELISA), and their correlations with CD4+ cell counts and viral loads were analyzed.

RESULTThe mean levels of MCP-1 were significantly higher and MSP were significantly lower in HIV-infected patients compared with the HIV-negative controls (P <0.01). After HAART for three months, there were no significant changes in the levels of these cytokines. But after long-term HAART (for 3 to 6 y), the level of MCP-1 was increased and that of MSP decreased significantly (P<0.01). There was a negative correlation between MSP and MCP-1 levels, and the same for MSP level and CD4+ cell counts; while there was a positive correlation between MCP-1 levels and CD4+ cell counts.

CONCLUSIONThe changed plasma levels of MSP and MCP-1 are associated with HIV-1 infection and HAART may reverse the levels of these two cytokines.

Acquired Immunodeficiency Syndrome ; blood ; drug therapy ; Adult ; Anti-HIV Agents ; therapeutic use ; Antiretroviral Therapy, Highly Active ; CD4 Lymphocyte Count ; Chemokine CCL2 ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Macrophage-Activating Factors ; blood ; Male ; Middle Aged ; Time Factors ; Treatment Outcome