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Human immunodeficiency virus (HIV) is an important challenge to human health. The patients with chronic infection have a gradually decrease of CD4+ T cells and eventually develop into acquired immunodeficiency syndrome (AIDS). Most HIV infected patients have received full virological suppression and immunological restoration due to antiretroviral therapy (ART), which improved their survival rate. After the initiation of ART, some patients get rapidly deteriorating clinical symptoms or even death, even though HIV replication is suppressed and CD4+ T lymphocytes raise, which called immune reconstruction inflammatory syndrome (IRIS). Clinical observations suggest that IRIS may be associated with a serious opportunistic infection and a very late onset of HIV/AIDS, but there are many unknowns from diagnosis to treatment and pathogenesis. This article reviews the incidence, the development of clinical features, related mechanisms and treatment strategies and other aspects of the disease.
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Objective To understand the dynamics of DC subsets in chronic HIV-infected patients during antiretroviral therapy (ART).Methods Seventeen treatment-naive chronic HIV-infected patients were enrolled in our study,and blood was collected at week 0,4,12,24,48 and 60 of ART.Additional 15 HIV-uninfected age-matched healthy adults and 15 long term non-progressors(LTNP) were recruited as controls.CD4+T cell counts and viral loads were examined routinely.The counts of DC subsets were measured by flow cytometry and IFN-α plasma levels were measured by ELISA.Data analysis was performed using SPSS version 16.0.Results ( 1 ) Before ART,mDC ( percentage and absolute count) in ⅢⅤ-infected group were significantly lower than those in healthy group and LTNP group,P＜0.001 in both groups.After 60 weeks of ART,mDC in HIV-infeeted group were significantly increased,and there were no significant differences compared with healthy controls and LTNP group.(2) pDC and IFN-α plasma levels remained relatively stable during ART,and similar to those in healthy controls and LTNP group.(3)Significant associations were found for DC subsets and CD4+ T cell counts before ART.mDC subsets at week 12,24,60 post ART were positively correlated with CD4+ T cell counts,and negntively correlated with virus load.Changes in mDC at week 8 post ART positively correlated with the changes in CD4+T cells at week 60 post ART,and negatively correlated with the changes in virus load at week 60 post ART.Conclusion The counts of mDC significantly reduced in HIV-infected patients,increased after ART,and positively correlated with CD4+ T cell counts.The findings suggest that mDC may play an important role in controlling HIV infection,mDC may serve as an early predictor for immune reconstitution in the initiation of ART.
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ObjectiveTo study HIV-1 DNA levels in different parts of HIV patients during the early stage of antiretroviral therapy.MethodsThe peripheral blood,gut associated lymphoid tissues and lymph nodes samples were collected before and 12 weeks after treatment in regular follow-up HIV-1/AIDS patients in Beijing Youan Hospital ( n =11 ).The average age was 39 years old ( 25 to 55 ).Mononuclear Cells were isolated by density gradient centrifugation and then used DNA extraction kit to extract DNA.Realtime quantitative polymerase chain reaction was used to examine HIV-1 DNA copy-number.Non-parametric test was used to analyse the differences of HIV-1 DNA copy numbers among groups.Results Before treatment,HIV-1 DNA copy-number in both gut associated lymphoid tissues ( 10 714 ± 2043 ) copies/106 cells and lymph nodes (9145 ± 1202) copies/106 cells were higher than that in the peripheral blood (66 ± 8) copies/106 cells ( U =0.00,P ＜0.05 ),There was no significant difference between lymph nodes and gut associated lymphoid tissues (U =46.00,P ＞0.05).After 12 weeks of treatment,HIV-1 DNA copy-number in both gut associated lymphoid tissues (1701 ± 790) copies/106 cells and lymph node (11 591 ± 1781 ) copies/106 cells were higher than the peripheral blood ( 18 ± 3 ) copies/106 cells ( Z =- 2.934,P ＜ 0.05 ).There was a significant reduction of DNA copy-number in gut associated lymphoid tissues and peripheral blood after treatment (Z =- 2.934,P ＜ 0.05 ).Conclusion Gut associated lymphoid tissues and lymph nodes may be important latent reservoirs for HIV-1 DNA.
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Objective To establish a mini-pool nucleic acid testing (NAT) assay using multiplex RT-nested PCR for the detection of HIV RNA, and apply it in screening for acute HIV infection among MSM. Methods Frozen EDTA plasma samples collected between Oct. 2008 and Mar. 2009 from 3 HIV infectors during window-period, a total of 30 HIV chronically infected individuals and 97 healthy subjects were used to develop the NAT assay. Plasma samples from 10 cases were pooled into one tube and centrifuged at high speed for the collection of viruses. HIV RNA was extracted. Two pairs of primers were designed according to two conserved regions of HIV RNA ( HXB2 nt 5783-nt 6228 and nt 1235-nt 2012).Multiplex RT-PCR and nested PCR were performed. Individual NAT-reactive samples were confirmed by commercially available NAT assays. The sensitivity and performance efficacy were also evaluated. The assay was then applied to 1 005 plasma specimens from MSM with negative or uncertain HIV antibody test results.These were collected in the same period as the other samples. Results ( 1 ) Two fragments of HIV were amplified successfully with the low detection limit of 162 copies/ml plasma; (2) Results of the mini-pool HIV NAT validation with samples from 3 HIV infectors during window-period were consistent with the expected values; (3) All 30 plasma samples from MSM with positive HIV antibody, which were tested by multiplex RT nested PCR, were found to be HIV RNA positive; (4) One out of 1 005 plasma samples was found to be HIV RNA positive, for this case acute infection was followed-up and sero-conversion was found. Conclusion Mini-pool NAT has good sensitivity, and may be applied to screening HIV RNA among MSM during window-period.
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Objective To investigate the expression of CD127 (interleukin-7 receptor α, IL-7Rα)and its association with apoptosis of CD8 + T lymphocytes in patients with chronic HIV-1 infection. Methods The expression of CD127 on T lymphocytes and spontaneous apoptosis of CD8+ T lymphocytes were measured by flow cytometry in peripheral blood from 24 patients with chronic HIV-1 infections and 12 healthy subjects. The associations of CD127 expression with CD4 +T lymphocytes counts, HIV RNA loads and cell apoptosis were analyzed. Mann-Whitney U test was performed to compare between the groups, and Spearman test was used for correlation analysis. Results The expression of CD127 on CD8 + T lymphocytes was significantly down-regulated in HIV-1 infected subjects (Z = -4.796, P ＜ 0. 01 ), which was positively correlated with CD4 + T lymphocytes (r = 0.817, P ＜ 0.01 ) and negatively correlated with HIV RNA load and CD8+T lymphocytes apoptosis (r= -0.442 and -0.688,P＜0.05 and ＜0.01). Conclusion CD127 down-regulation may play an important role in the descended ability of receiving survival signals and ascended apoptosis of CD8 + T lymphocytes during chronic HIV-1 infection, which indicates that IL-7 might be a novel strategy in treatment of HIV infection.
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CD4+CD25+ Regulatory T cells (Treg) have been found to down-regulate immune activation in HIV-1 infection. However, whether the depletion of Treg benefits to the disease status of HIV infection remains undefined. To address this issue, we enumerated the Treg absolute counts and frequency in 75 antiviral-na(i)ve HIV-1-infected individuals in this study. It was found that HIV-infected patients displayed a significant decline in Treg absolute counts but a significant increase in Treg frequency. In addition, with disease progression indicated by CD4 T-cell absolute counts, circulating Treg frequency gradually increased; while Treg absolute counts were gradually decreased, suggesting that the alteration of Treg number closely correlated with disease progression in HIV infection.Functional analysis further showed that Treg efficiently inhibit both CD4 and CD8 T cell proliferation in vitro. Thus, our findings indicates that Treg actively participate in pathogenesis of chronic HIV infection,influencing the disease progression.
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A variety of opportunistic infections can occur in the late-stage of HIV-1 infection,Mycobacterium avium complex (MAC) infection is a common cause of disseminated bacterial infection. Since the advent of highly active antiretroviral therapy (HAART),the rate of MAC infection has declined substantially,but there is risk in individuals with low CD4 cell counts. This article describes the epidemiological,clinical,therapeutic and preventive aspects of MAC infection in HIV-sero-positive individuals.