Objective To observe secretive ability of three C-C chemokines, macrophage inflammatory protein-1?(MIP-1?),MIP-1? and regulated-upon activation.normal T-cell expressed and secretory factor(RANTES)by lympocytes and moncytes of cord blood from chinese necnates and peripheral blood from chinese adults.Method Using Ficoll density-gradient centrifugation and gelatin-coated flask,the Iympocytes and monocytes were isolated from cord blood samples of seventeen Chinese neonates and peripheral blood samples of twenty Chinese adults.Purified lymphocytes and monocytes were incubated with PMA and LPS,respectively.Supernants were tested by ELISA for concentrations of MIP-1?,MIP-1? and RANTES.Results Concentrations of MIP-1?, MIP-1? and RANTES in cord blood lymphocyte and monocyte were (3920?730)pg/ml, (4910?590)pg/ml,(1470?410)pg/ml,(3240?980)pg/ml,(1960?1300)pg/ml and (240?120)pg/ml,respectively,and in adults peripheral blood were (6560?840)pg/ml,(5810?1150)pg/ml,(2250?570)pg/ml,(3010?1350) pg/ml,(2280?870)pg/ml,(690?430)pg/ml,respectively.Cord blood lymphocyte and monocyte showed diminished ability to secrete RANTES than adult peripheral blood.Conclusions The diminished RANTES secretion of cord blood lymphocyte and monocyte may be releted to the pathogenesis of Chinese neonatal HIV infection,and indicated some immunotherapies are feasible for preventing neonate from HIV mother-to-child transmission.

Objective To obserre antiviral effect, immune rebuilding efficacy and side effects of didonosine, stavudine and nevirapine combination therapy for human immunodeficiency virus (HIV) type 1 infection. Methods Three medicines were administered for 8 HIV-1 infected cases. Plasma HIV RNA load, and the levels of CD 4 + T cell and CD 8 + T cell were detected before starting treatment and 4,12 and 24 weeks after starting treatment. Side effects and changes in laboratory's examinations were observed during the trial. Results After 12 and 24 week treatment, the plasma HIV-1 level reduced 2 28 logs and 2 63 logs, from a mean baseline of (283,125?187,217) copies/ml to (1,501?930) copies/ml and (669?477) copies/ml, the CD 4 + T cell counts increased from a mean baseline of (337?221) cells/ml to (393?301) cells/ml and (414?284) cells/ml, and CD 8 + T cell counts decreased from a mean baseline of (918?371) cells/ml to (823?315) cells/ml (812?305) cells/ml, respectively. Part of cases occurred mild or medium rash, nausea, headache, fatique, abdomina1 pain and diarrhea, and had blood transaminase increased, and leucocyte and hemoglobin decreased. Conclusions Didonosine, stavudine and nevirapine showed high anti-HIV and immune rebuilding effects in highly active antiretroviral therapy (HAART). The medicine regimen was well tolerated in a six-month clinical trial.

Objective To determine the incidence, clinical manifestation and risk factors of immune reconstitution inflammatory syndromes (IRIS) in highly active antirctroviral therapy (HAART) for HIV/AIDS patients. Methods Two hundred and twelve HIV/AIDS patients received HAART, and were followed up for 6 months. The incidence time and disease spectrum of IRIS were observed. Multiple logistic regression analysis was performed to identify the risk factors for IRIS. Results Among 212 patients, there were 59 (27.8%) experienced an IRIS event during the first 6 months of HAART, 2 of which died (2/59,3.39% ). Median time of IRIS onset was 21 days form HAART initiation. The disease spectrum included tuberculosis, herpes virus infections, pneumocystis jirovecii pneumonia, cryptococcal meningitis and penicillium marneffei infection. Risk factors of IRIS included baseline infections ( OR = 1. 655, P =0.010),fever during HAART ( OR = 2. 344, P= 0.006), and baseline CD4 + count ( OR = 1. 556, P = 0. 034).Conclusions IRIS usually occurred within the first month from HAART initiation, and tuberculosis and herpes virus infection are most common. The occurrence of IRIS is associated with the antigens burden and the decreased baseline CD4 + count.

To investigate the dynamics of interleukin-21 (IL-21) cytokine in the Chinese HIV patients undergoing highly active antiretroviral therapy (HAAPT).Methods A total of 25 adults with chronic HIV infections,responding to combined highly active antiretroviral therapy (HAART) guideline criteria were enrolled for a 1-year follow-up.After signing an informed consent,20 mL blood was collected from each patient at the base line,6 month and 12 month,respectively.CD4 and CD8 cell count was quantified by flux cytometry,serum HIV RNA quantified by real time PCR and IL-21 concentrations by ELISA.Results IL-21 levels increased gradually during the follow-up but did not reach the healthy levels.IL-21 correlated positively with the CD4 cells but not with CD8 T cells.HIV RNA correlated negatively with CD4 cell count but did not show any relationship with the CD8 cells.Conclusion IL-21 has potential role in the immunopathogenesis of HIV,and might be an important factor in immune construction during HAART.

Objective To compare the mutation sites in human immunodefieiency virus type 1 (HIV-1) vpr gene via of HIV-1 infected individuals from different regions in China with the previous studies, and to provide information for the further study on the relationship between HIV-1 vpr gene mutations and clinical conditions of the patients. Methods Reverse transcription-polymerasc chain reaction (RT-PCR) and nested PCR were used to amplify HIV-1 vpr gene of 398 HIV-1 infected individuals. The amino acid sequences were analyzed to determine polymorphisms, deviation rate and common mutation sites of HIV-1 vpr gene. Meanwhile, the viral load, subsets of lymphocytes and clinical course of patients infected with mutated HIV-1 were analyzed. Results One hundred and fifty three positive samples which were obtained from 398 HIV-1 infected individuals were available for further analysis. The amino acids sequence typing of HIV-1 Vpr were showed that CRF01 AE was 51.63%, subtype C 24.84%, subtype B 17.65%, CRF03_ AB 3.92% and CRF08 BC 1.31%. Eighty four point three percent of 77th amino acid of HIV Vpr sequence was glutamic acid which was significantly different from what overseas researches reported that the R77Q mutation was correlated with long-term non-progression (LTNP) of AIDS. The mutations of the, 63th, 70th, 85th, 86th, 89th and 94th amino acids of HIV Vpr were likely related to the clinical remission of HIV-1 infected individuals. Conclusions M group is the main type of HIV Vpr typing in China, and CRF01 AE is predominant. Some amino acid mutation sites of HIV-1 Vpr are possibly correlated with clinical manifestations of HIV-1 infected individuals.

Objective To observe that antiretroviral efficacy, immune reconstitution of four-year highly active antiretroviral therapy (HAART), and evaluate its side effect in Chinese HIV-1-infected patients. Methods A total of 258 HIV-1 infected patients, given HAART regimens composed of two nucleoside reverse transcriptase inhibitor (NRTI) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) for mean 51.5 months, measured HIV RNA viral load(VL) and the counts of CD4+ T cell,CD8+ T cell at the baseline and 6, 12, 24, 36 and 48 months after HAART initiation, respectively,monitoring side effect, blood routine, main biochemical parameters, and other disadvantageous accidents during the 51.5-month treatment. Results Plasma HIV-1 RNA level was determined by fluorescent quantitative polymerase chain reactions (FQ-PCR) at the baseline and 6, 12, 24, 36 and 48 months after starting HAART, and showed 5.27, 2.97, 2. 74, 2. 62, 2. 67 and 2.75 lg (copies/ml), respectively. The counts of CD4+ T cell from (127±63) cells/μl at the baseline increased to (190±115), (248±93),(269±127), (296 ± 156) and (317 ± 195) cells/μl at 6, 12, 24, 36 and 48 months after starting HAART. A total of 149 treated patients (57.8%)had gastrointestinal side effects, peripheral polyneuropathy, various rashes, central nervous system disorders, fever or baldness. Twenty-two patients changed one of three medicines to another because toxicity. Sixteen changed the regimen to the second line HAART for lactic acidosis or other serious toxicities. Conclusions A total of 258 HIV-1 infected Chinese patients treated with two NRTI and one NNRTI as first line HAART regimen during mean 51.5 months,showed a good antiretroviral efficacy and immune reconstitution, but a few site-effects at the parts of patients. It is necessary to treat adverse effect and change HAART regimen for severe toxicity in time.

Objective To determine the incidence, clinical manifestation and part of lymphokines which represent the balance of Th1 and Th2 in the role of the immunologic mechanisms for IRIS(immune restoration inflammatory syndromes)in patients initiating HAART(Highly Active Antiretroviral Therapy).Methods A prospective study of all patients initiating HAART was performed. A period of six months tracking initiating HAART was performed. The incidence of IRIS, time of occurrence and clinical disease spectrum were recorded. The main T lymphokines including IL-2, INF-γ, IL-4, IL-10 which on behalf of the balance of Th1 and Th2 were detected. To explore the immunopathologic mechanisms for IRIS, the levels of T lymphokines at pre-HAART, initiating HAART for 1 month, 3months and 6 months were compared in IRIS group and non-IRIS group, healthy group. Results A total of 212 patients were enrolled in this study. 59 patients were diagnosed as IRIS at a median of 21 days after HAART initiation (QR 19 days).The main disease spectrum included tuberculosis, herpes virus infections, pneumocystis jirovecii pneumonia. No matter in the IRIS group or non-IRIS group, the main lymphokines baseline of IL-2, INF-γ reduced and IL-4, IL-10 increased before HAART compared to healthy group (P ＜ 0. 05), which had the tendency to restore balance relations initiating HAART. The lymphokines levels had significant difference between baseline and 6 months initiating HAART (P ＜ 0. 05). The changed levels of lymphokines between IRIS group and non-IRIS group before HAART had significant difference compared to healthy group. IL-2, INF-γ increased level[(11.68 ± 2. 89) pg/ml vs (8.52 ±2.26) pg/ml; (22. 19 ± 6. 22) pg/ml vs (18.34 ±5. 35) pg/ml] and IL-10 decreased level [(19. 21 ± 4. 03) pg/ml vs (23. 19 ± 5.92) pg/ml] had significant difference between IRIS group and non-IRIS group initiating HAART I month(P ＜0. 05). Conclusions The incidence of IRIS during 6 months initiating HAART in HIV/AIDS was 27. 8%, IRIS usually occurred in 1 month initiating HAART. The most common disease spectrum was infectious disease, including tuberculosis and herpes virus infection. Lymphokine of Th1 and Th2 existed unbalance in IRIS group and non-IRIS group before HAART. The unbalance tendency in IRIS group was more obvious. All lymphokines had the trend to recover balance. IL-2, INF-γ significantly increased and IL-10 significantly decreased, which might involve the occurrence of the IRIS.

Objective To investigate the regulatory effects of IFN-γon Treg cells from HIV/AIDS patients receiving highly active antiretroviral therapy (HAART) for one year.Methods Thirty HIV/A1DS patients whose CD4+T cells were below 350/μ1 were recruited for HAART therapy.Blood samples were collected at the time points of 0,24,48 weeks after HAART.PBMCs were isolated and randomly divided into two culture groups.One group was cultured directly in medium and another group was co-cultured with IFN-γ (40 pg/ml).The supernatants and cells were separated after 5 days of culture for analysis.The concentrations of IL-12 and CD4+CD25+Foxp3 Treg cells were measured by ELISA and flow cytometry,respectively.Results The levels of IL-12 in the supernatants from the culture without IFN-γ at time points of 0,24,48 weeks after HAART were lower than those from the co-cultured group [(37.02±12.76) vs (41.79± 15.02),t=2.336,P=0.03; (41.76±17.01) vs (47.2±14.26),t=2.702,P=0.014; (48.01± 11.84) vs (53.44± 11.30),t =3.14,P =0.003].The percentages of CD4+ CD25 + Foxp3 Treg cells in CD4+ T cells from the direct-cultured group were higher than those from the co-cultured group at the three time points [(10.41±1.10)％ vs (2.40±1.11)％,t=13.89,P=0.000; (8.33±2.03)％ vs (1.99± 0.86)％,t=12.93,P=0.000; (5.65±1.55)％ vs (1.32±0.73)％,t=10.61,P=0.000].Moreover,the results within the same group at the time points of 0,24,48 weeks upon HAART were also significantly different.Conclusion With the interference of HAART,IL-12 levels were increased,while CD4+CD25+ Foxp3 Treg cells were decreased in patients with HIV/AIDS.IFN-γ plays an important role in this process.

Although highly active antiretroviral therapy (HAART) can effectively reduce the HIV replication,complete recovery of CD4+ T cells does not always occur,even among patients with high virological control.Current researches on γ-chain cytokines have understood the biology and their crucial roles in initiating,maintaining,and regulating the immunologic homeostasis and the inflammatory processes.Due to the multiple functions such as the regulatory and effector cellular function in healthy and disease state,these molecules,their receptors,and their signal transduction pathways are promising candidates for therapeutic interference.The common γ-chain cytokines IL-2,IL-7,IL-15,and IL-21 are primary regulators of T cell homeostasis and thus have been considered prime immunotherapeutic candidates,both for increasing T cell levels/function and augmenting vaccine-elicited viral-specific T cell responses in immunocompromised AIDS patients.The objective of this review is to update the role of the common γ-chain cytokines IL-2,IL-7,IL-15,and IL-21 in HIV AIDS pathogenesis.

Objective To explore ability of the vpr gene of human immunodeficiency virus type 1 ( HIV-1 vpr) to induce cell G_2 arrest and apoptosis, and the influence when it mutated, the relationship between Vpr-induced G_2 arrest and apoptosis inductions. Methods Fourteen mutant vpr fragments selected from Chinese patients with HIV. Both eukaryotic expression vector pcDNA3.1( + ) and PCR products purified, double-cut by Hind Ⅲ and BamH Ⅰ and the cut products legated and transformed into competent cells JM109. The 14 reconstructed plasmids electronically transfected into Jurkat-cells, and established cells with pcDNA3. 1-vpr , pcDNA3. 1-vpr-Fs and pcDNA3. 1 blank cells, and without pcDNA3. 1 cell. Cells were harvested after 24 h. mRNA expression was detected by RT-PCR, the DNA content and percentage of apoptosis were monitored by flow cytometry. Results Transfected with 14 mutant HIV-1 Vpr protein, cells display different G_2 percentage and apoptosis ratio. HIV-1 vpr induce cell cycle G_2 arrest and apoptosis, wherase Vpr Fs with a C-terminal end truncation, vector pcDNA3.1( + ) and the blank cells can not. The G_2 percentage and apoptosis ratio reduced when transfected with vpr expressing mutating of 70V, 85P, 86G, 94G compared to the wild type. Subtype AE has a weaker potential to induce cell cycle G_2 arrest and apoptosis. Preliminary, we find that the higher G_2 percentage followed the higher ratio of apoptosis. Conclusion HIV-1 vpr can induce cell cycle G_2 arrest and apoptosis, wherase Vpr Fs with a C-terminal end truncation can not. We firstly found that mutated sites of 70V, 85P, 86G, 94G may reduce the ability of Vpr to induce cell cycle G_2 arrest and apoptosis, subtype AE of vpr in Chinese HIV-1 patients has a weaker potential to induce cell cycle G_2 arrest and apoptosis. Analysis of various mutations in the vpr gene revealed that the extent of Vpr-induced G_2 arrest correlated with the levels of apoptosis. And investigate the pathegenesis of HIV vpr. This can also make a good foundation for further study on gene therapy.