Soluble tumour necrosis factor receptors (sTNF-R) and HIV infection: correlation to CD8+ lymphocytes.

The objective of this study was to determine sTNF-R, type I (p55) and type II (p75) in sera of HIV-infected male homosexuals and correlate them to T lymphocyte subpopulations and course of HIV infection. Serum samples were obtained from 39 HIV-1+ asymptomatic male homosexuals, 10 symptomatic (ARC and AIDS) male homosexuals and 44 HIV- non-homosexual healthy controls. sTNF-R levels were determined by ELISA with specific MoAbs and polyclonal antibodies to the sTNF-R proteins. sTNF-RI and II levels were significantly elevated in 72% and 74% respectively of HIV+ asymptomatic male homosexuals and in all of the symptomatic male homosexuals. In sequential studies a highly significant positive correlation was found between sTNF-RI and sTNF-RII (r = 0.8, P < 0.001) and between both sTNF-R and CD8+ lymphocyte counts (r = 0.6 and 0.92, respectively, P < 0.01-0.001) during the asymptomatic stage of the infection. All these correlations were lost, however, during the symptomatic phase of the disease. These results suggest that: (i) HIV infection is associated with elevation of sTNF-R serum levels; (ii) sTNF-R levels are strongly correlated to CD8+ lymphocytes during the asymptomatic stage of HIV infection.     

Biological significance of the antibody response to HIV antigens expressed on the cell surface

Summary Human antibodies to HIV antigens expressed on the surface of infected cells may inhibit cell fusion with uninfected CD 4-positive cells and mediate killing of the infected cells by effector cells bearing the Fc receptor.Sequential sera from ten HIV-antibody seroconverted men, of which five progressed to ARC or AIDS (CDC stage IV) during the follow-up period of two years, were tested for the ability to inhibit CD 4-dependent cell fusion, (CFI) and to mediate antibody-dependent cellular cytotoxicity (ADCC).Nine patients developed HIV-specific ADCC and seven CFI-antibodies using the HIV strain HTLV-IIIB as target antigen. These antibodies appeared approximately at the same time 2–12 months after primary infection, defined as antibody seroconversion or antigenaemia. ADCC antibodies were detectable at higher titers as compared to CFI-antibodies. All sera of asymptomatic individuals (CDC stage II and III) were CFI antibody positive and had a higher mean ADCC titer as compared to sera from patients progressing to AIDS or ARC.ADCC and CFI antibodies coincided in some cases in the complete absence of core antibodies. Because the relationship between ADCC and CFI was not exclusive it is concluded that distinct domains of the HIV envelope induce natural antibodies mediating ADCC and CFI.     

Immune responses to fractionated cytomegalovirus (CMV) antigens after HIV infection. Loss of cellular and humoral reactivity to antigens recognized by HIV-, CMV+ individuals.

In order to delineate the molecular pathogenesis of the increased susceptibility to CMV disease in HIV infection, the patterns of antigen responsiveness in HIV-infected and non-infected individuals were investigated. CMV was fractionated by SDS-PAGE and electroblotted onto nitrocellulose. Lymphoproliferative responses of healthy HIV-, CMV+ individuals and HIV+, CMV+ asymptomatic patients to a whole CMV antigen preparation and to 20 fractions of nitrocellulose-bound CMV were then compared. Three fractions of approximate molecular weight of 130-165, 65-75, and 55-65 kD appeared to contain the major T cell stimulating antigens for HIV-, CMV+ individuals. A statistically significant depression of responses to fractions containing antigens in the ranges of 130-165 kD and 55-65 kD but not to whole CMV was seen in HIV+ individuals compared with controls. In healthy controls, the sum of the proliferative responses as measured by 3H-thymidine uptake to these three major fractions was approximately equal to the response to a whole CMV antigen preparation, whereas it was less than half of this response in five out of six HIV+ subjects. When antibody activities to CMV antigens were analysed by immunoblotting of sera from the two subject groups and also sera of ARC and AIDS patients, a selective loss of reactivity was revealed in 10 out of 19 HIV+ subjects to a band of 26-28 kD whereas all 15 HIV-, CMV+ controls recognized this band. Serum IgG and IgM values were both significantly higher in HIV+ individuals than in controls. These findings suggest that specific lesions in the repertoire of immune responsiveness to CMV antigens occur in HIV+ individuals.     

Peripheral blood monocytes derived from HIV+ individuals mediate antibody-dependent cellular cytotoxicity (ADCC)

Monocytes/macrophages serve a number of immunologic functions and play a major role in the host defense against infection. Abnormal functions of monocytes have been reported in AIDS and HIV+ individuals. A recent report from our laboratory demonstrated that peripheral blood monocytes (PBM) derived from AIDS patients were de novo "activated" as assessed by direct cell-mediated cytotoxicity (CMC) and secretion of cytotoxic factors and tumor necrosis factor-alpha (TNF alpha). Thus, both the direct cytotoxicity as well as the antibody-dependent cellular cytotoxicity (ADCC) exerted by the monocytes may contribute to the destruction of HIV-infected/coated cells and the immunopathogenesis of AIDS. The present study investigated the ability of HIV+ PBM to mediate ADCC against antibody-coated target cells in an 18-hr 51Cr release assay. Initial studies examined ADCC using a macrophage resistant target Raji and rabbit anti-Raji serum. The results show that the majority of PBM from HIV+ individuals mediate ADCC activity while the majority of PBM from normal healthy controls was not cytotoxic. While activation of PBM with recombinant interferon-gamma (rIFN-gamma) enhances the ADCC activity of normal PBM, treatment of HIV+ PBM with IFN-gamma resulted in significant enhancement of ADCC. Both untreated and treated PBM from HIV+ individuals had significantly higher ADCC than PBM from normal individuals. Of interest, a significant ADCC activity was found by PBM derived from two HIV- high risk individuals whether untreated or treated with rIFN-gamma. The ADCC results with RAJI target cells prompted us to investigate whether ADCC can also be obtained using HIV-infected T4+ cells. We selected a macrophage and TNF resistant T4+ CEM cell line as target for ADCC. The target was coated with inactivated HIV and pooled human anti-HIV serum was used. Studies with a few HIV+ individuals demonstrate that significant ADCC is obtained with PBM from HIV+ individuals but little or no ADCC by normal PBM and the ADCC was specific for HIV. The ADCC was also significantly enhanced by treatment of PBM with rIFN-gamma. The results of this study clearly indicate that PBM from HIV+ individuals are endowed with the capacity to mediate ADCC against HIV-infected/coated cells and thus, we postulate that PBM may play a direct role in vivo in lysis or suppression of HIV-coated/infected cells and in the pathogenesis of AIDS.     

Immunoglobulin and complement complexes in blood following infection with human immunodeficiency virus type 1.

Freely soluble and complexed plasma immunoglobulin A (IgA), IgG, IgM, C1q, C3, and factor B in 36 human immunodeficiency virus type I (HIV-1)-seronegative controls, 69 asymptomatic HIV+ subjects, and 117 individuals with symptomatic HIV-associated disease were characterized. Levels of free and complexed IgG and IgA, and to a lesser extent free C1q and complexed IgM, increased with HIV-1 infection. In stark contrast, both HIV+ groups showed three- to sixfold declines in complexed C3, C1q, and factor B levels. The asymptomatic HIV+ population showed declines in levels of C3-bound IgA, IgG2, and IgG4 complexes. The asymptomatic group showed reductions in C3-complexed IgM, IgA, IgG2, and IgG4 levels. HIV infection is associated with complement-deficient immune complexes.     

Complement-mediated enhancement of HIV-1 neutralisation by anti-HLA antibodies derived from polytransfused patients

We have recently shown that 'alloimmune sera' derived from polytransfused patients (PTP sera) are able to recognise and neutralise HIV in vitro. In this study we try to identify the protein(s), which are recognised by the PTP sera and elucidate mechanisms responsible for the neutralising capacity of these sera. The PTP sera allowed immunoprecipitation (IP) of HLA class II molecules on HIV-infected cells. To detect a potential cross-reactivity of alloreactive antibodies (Ab) with the HIV envelope protein gp160 or its subunits gp120/gp41 and HLA proteins, ELISA and FACS analyses were performed. The lack of reactivity of the PTP sera against rsgp160 in ELISA or FACS analysis indicated that recognition of cells was independent of HIV infection. To clarify whether interaction of the PTP sera with target cells has any effect on the infection process, virus neutralisation assays were performed. Inhibition of HIV infection was observed only when virus was pre-incubated with the PTP sera. Complement enhanced neutralisation of HIV-1 significantly. This enhancement was not due to complement-mediated lysis, because pre-incubation of the target cells with PTP sera did not inhibit HIV replication. Therefore, the neutralising effect of the Ab was due to blocking of the viral attachment/fusion process and not to negative signalling after infection. Since steric hindrance is possible only when HLA and gp120/gp41 are in close vicinity, isolation of rafts and IP assays were performed. These experiments revealed that gp120 and MHC class II molecules are indeed co-localised. The close physical association of gp120/gp41 and HLA strongly supports a mechanism for neutralisation of HIV by anti-HLA-Ab based on steric hindrance.     

Serum and effector-cell antibody-dependent cellular cytotoxicity (ADCC) activity remains high during human immunodeficiency virus (HIV) disease progression

The activity of both serum and effector cell antibody-dependent cellular cytotoxicity (ADCC) against human immunodeficiency virus (HIV-1, HIV) was assessed in HIV-infected individuals. The goal was to relate ADCC levels with the stage or progression of HIV disease. Serial serum samples, usually collected at 6-month intervals, from individuals at defined stages of HIV disease (sero-conversion, the HIV-seropositive period before AIDS, and around the time of clinical AIDS diagnosis) were tested. HIV-coated CEM tumor cells were used as targets. Effector-cell ADCC activity was evaluated using fresh peripheral blood mononuclear cells (PBMC) from HIV-infected individuals at different stages of HIV disease. Samples were obtained from male homosexual participants in the Multicenter AIDS Cohort Study (MACS). In seroconverters, ADCC-inducing HIV-specific antibodies were detected at the time that the ELISA antibody test was first positive. Within several months, serum ADCC activity stabilized in each individual. In 29 HIV-seroprevalent individuals (HIV seropositive on their first visit), serum ADCC activity remained constant regardless of whether the individual's HIV disease was stable (high stable CD4;n=9) or rapidly deteriorating (sharply declining CD4,n=10; AIDS progressors,n=10). With respect to effector-cell activity, PBMC from HIV-infected individuals with or without AIDS were capable of mediating ADCC with heterologous and usually with autologous sera. Although the level of NK cytotoxic activity and the level of antibody-armed effector cell activity have been reported to decline as disease progresses, our results support previous observations that ADCC effector-cell activity against antibody-coated targets does not decline in HIV infection. These results indicate that both serum and effector cells with ADCC activity are present in HIV-infected individuals shortly after seroconversion and are maintained throughout HIV disease. Although levels of serum and effector-cell ADCC activity do not predict whether an individual will develop AIDS, CD4 cells which express HIV antigens (either produced endogenously or adsorbed onto the surface) could serve as targets for anti-HIV-mediated ADCCin vivo. ADCC could, thereby, contribute to CD4 T-cell depletion in infected individuals. However, since serum and effector-cell ADCC levels do not seem to relate to disease stage or progression, the protective or pathogenic role that ADCC plays in HIV-disease remains unresolved.     

CD80 expression is decreased in hyperplastic lymph nodes of HIV+ patients

A centrofollicular hyperplasia is present within secondary lymphoid organs during all the asymptomatic phase of the HIV disease. Although this hyperplasia has been well characterized by histological studies, the nature of the phenotypic alterations in B cell populations occurring within HIV+ lymphoid organs remains to be established. By immunohistochemistry, we thus investigated whether a particular germinal center (GC) B cell population was increased during HIV-induced hyperplasia and whether any phenotypic change was specific to HIV-1 infection. As compared to normal tonsils (three cases) and HIV- hyperplastic lymph nodes (eight patients), we observed a loss of GC polarization in all HIV+ sections (11 patients), with no more delineation between dark and light zones, as shown by Ki67, CD10, CD77, CD95 and CD86 staining. In contrast to CD86 expression which remained as intensive in HIV+ as in HIV- lymph nodes, CD80 staining was strongly decreased in GC of HIV+ lymph nodes but not in their extrafollicular zones. The loss of CD80 expression from CD19+ B cells was also observed by cytometric analysis of cell suspensions of three HIV+ patients. Although we found no evidence of an increase in a particular GC B cell subset in HIV-1-induced hyperplasia, the strong GC disorganization observed may induce impaired cell-cell interactions and thus participate in the loss of CD80 antigen. In contrast to HIV- situations where CD80 and CD86 was similarly expressed on B cells, the lower level of CD80 expression in HIV+ GC may favor Th2 T cell responses through CD86-CD28 interactions.      

Comparison of human immunodeficiency virus (HIV)-specific infection-enhancing and -inhibiting antibodies in AIDS patients

The humoral immune response of the human host against the human immunodeficiency virus (HIV) type 1 (HIV-1) envelope glycoproteins comprises virus-neutralizing antibodies (NAs), antibody-dependent cellular cytotoxicity-mediating (ADCC) antibodies, and infection-enhancing antibodies (IEAs). Because of their potential significance for the outcome of infection with this virus, we have studied the relative prevalence of NAs, ADCC antibodies, and IEAs in the sera of patients infected with HIV. Our results demonstrate that while >or=60% of serum samples are positive for NAs or ADCC antibodies, 72% of these serum samples mediate the enhancement of infection in the presence of complement. In patients with low CD4 counts, NA and ADCC antibody levels tend to decrease, while IEA levels increase. A significant positive correlation was found only between the presence of ADCC antibodies and the presence of antibodies that neutralized HIV-1 in the presence of complement. These results show that the anti-HIV-1 humoral immune response consists of a mixture of antibodies that may inhibit or enhance HIV infection and whose ratios may vary in different stages of the infection.     

Autoantibodies in male homosexuals and HIV infection

We have used ELISA to study the frequency of autoantibodies to several antigens in the serum of 17 male homosexuals (MHS) negative for HIV (HIV-), 11 asymptomatic HIV seropositive MHS (HIV+) and patients with ARC (N = 15) or AIDS (N = 13), and compared them to 20 matched healthy heterosexual controls. Serum antibody binding to histones, cardiolipin, ss-A, ss-B and Sm was found to be significantly higher in each of the MHS groups studied as compared to controls (P less than 0.001), and was also increased in the HIV+ patients vs. the HIV- group (P less than 0.05). In contrast, no increase in autoantibodies to ss-DNA, ds-DNA, poly(I), poly(G) or RNP were found in any of the groups tested. These results enlarge the spectrum of autoimmunity previously reported in HIV infection and identify a similar pattern to a lesser degree, already present in HIV- MHS, suggesting a role for HIV or concomitant virus infections in its pathogenesis.     

Evaluation of the performance of a new automated HIV combination assay

BackgroundMore and more countries test for HIV infection using combination assays that simultaneously detect p24 antigen and HIV antibodies.ObjectiveTo assess the performance of a new HIV combo assay: LIAISON^® XL murex HIV Ab/Ag HT.Study designThe assays were examined with a total of 3090 samples that included 769 selected HIV antibody-negative samples, 1849 unselected HIV samples, 15 HIV-1 p24 Ag reference samples, 90 primary HIV-1 infection (PHI) samples, 167 HIV-1 antibody-positive samples (well characterized of groups M and O), 95 HIV-1 antibody-positive samples and 105 HIV-2 antibody-positive samples.ResultsThe specificity of the LIAISON^® XL murex HIV Ab/Ag HT was 99.7%. The analytical sensitivity of Ag p24 of the LIAISON^® XL murex HIV Ab/Ag HT was 0.58 IU/mL and 9.93 pg/mL when using WHO and French national standards, respectively. All screened HIV subtypes was identified by this assay. Also, 90 PHI specimens were detected by this screening assay.ConclusionThe sensitivity and specificity of the LIAISON^® XL murex HIV Ab/Ag HT assay are high. Hence the assay offers automated high-throughput screening with ability to detect primary infection.     

HIV antigen detection in circulating immune complexes

Various methods were evaluated for their effectiveness in releasing HIV antigen (Ag) from artificial immune complexes (IC) and from IC present in serum from HIV antibody (Ab) positive subjects. The most effective methods for recovering HIV Ag from IC were those which included a denaturation step to prevent reassociation of Ag with Ab. IC precipitation in 2.5% polyethylene glycol followed by acid treatment with 1 M glycine.HCl (pH 2) for 10 min at 70 degrees C in the presence of 0.05% SDS gave very satisfactory results. With this method, IC were detected in sera from HIV antibody positive Caucasian subjects at all stages of infection. After HIV IC dissociation, HIV Ag was detected in a significant number (8/17 or 47%) of asymptomatic subjects. IC were most prevalent during the late stages of infection. A substantial increase in HIV Ag positivity was also observed in 20 Senegalese HIV Ab positive sera. After HIV IC dissociation HIV antigen detection increased from 2/20 to 12/20. The relevance of IC detection is discussed.     

Antibody-dependent cellular cytotoxicity mediated by CD16+ lymphocytes from HIV-seropositive homosexual men

We investigated the ability of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-seropositive asymptomatic and mildly symptomatic homosexual men with known time of seroconversion to mediate antibody-dependent cellular cytotoxicity (ADCC) specific for HIV. PBMC from HIV-seronegative and -sero-positive subjects lysed T (CEM) cells persistently infected with HIV to a significantly greater degree than uninfected CEM cells in the presence of HIV antibody-positive serum in a 4-hr 51Cr release assay. The response was mediated by CD16+ cells. ADCC responses were lower in PBMC of 13 men tested 9 to 25 months (average, 16.1 months) after seroconversion to HIV as compared with seronegative subjects, and were further decreased in 11 men tested 26 to 38 months (average, 31.6 months) after seroconversion. Decreases in numbers of circulating CD16+ cells appeared to contribute to depression in ADCC activity. The suppressive effect of HIV infection on ADCC effector cell activity may be important in the immunopathogenesis of acquired immune deficiency syndrome.     

Virological exploration of individuals with discordant HIV screening tests.

Screening for HIV infection can use many algorithms. When two different HIV antibody assays are used, discordant results may occur. To discriminate between HIV seroconversion, HIV variant infection and false positive reactivity, 30 consecutive subjects with two discordant HIV antibody-screening assays were extensively investigated for HIV infection. No subject had HIV seroconversion or reached HIV seropositivity criteria after a follow-up of 3 months. By contrast 36% became HIV negative by the use of both HIV screening assays. p24 Antigen, HIV-1 RNA, HIV-1 DNA, HIV-2 DNA assays and HIV isolation by sensitive culture were unable to identify HIV infection in the 30 subjects with discordant HIV screening assays. The data suggest that the use of two HIV screening assays increase false-positive HIV results without increasing clinical sensitivity. To compliment follow-up of HIV screening, early testing for HIV RNA could be useful to identify or eliminate a recent infection.     

Field evaluation of the Abbott ARCHITECT HIV Ag/Ab Combo immunoassay

BackgroundFourth generation assays for HIV diagnosis are progressively being introduced into routine services, due to their improvement of diagnosis. In spite of this, HIV diagnosis remains a challenge in sub-Saharan Africa, due to false positive reactivity. There is a continuous need for field evaluations and routine validations of fourth generation HIV tests in African populations.ObjectivesEvaluate the performances of the ARCHITECT HIV Ag/Ab kit (Abbott) in a population living in an African setting-Cameroon compared to a population living in a European setting-France.Study design645 HIV samples from both France and Cameroon were evaluated. The positive panel (378 samples) included a diverse series of HIV-1 variants (groups M, N, O, and P) as well as HIV-2 samples. Results were compared to original diagnosis done with other 4th generation assays (AxSYM HIV Ag/Ab (Abbott) and Vidas HIV DUO QUICK) (bioMérieux).ResultsSensitivity of the ARCHITECT was 100% in both sites. It diagnosed all variants of the panel with different reactivity profiles following strain diversity. A wider range of reactivity was observed for group O. Specificity was slightly lower (97.6%) in Cameroon than in France (98.6%), probably due to a higher rate of false positive reactivity. ARCHITECT HIV Ag/Ab assay had high performances in clinical sensitivity and specificity and is adapted to the wide genetic diversity of viruses circulating in West Central Africa.ConclusionOur results further highlight the need to evaluate HIV diagnostic tests before introduction into routine diagnostic services both in the North and in the South.     

Relation between HIV-2 proviral load and CD4+ lymphocyte count differs in monotypic and dual HIV infections

OBJECTIVE: To explore and compare the relations between proviral DNA load and CD4+ lymphocyte counts in both HIV-2 monotypic and HIV dual infection. STUDY DESIGN/METHODS: In Dakar, Senegal, where the HIV-1 and HIV-2 epidemics overlap, serum and peripheral blood mononuclear cell (PBMC) DNA samples were collected from registered female sex workers and hospitalized patients. Sera were evaluated for reactivity to antigens of HIV-1 and HIV-2 by immunoblot; dual reactivity was confirmed with recombinant envelope peptides for HIV-1 and HIV-2. These samples were then subjected to HIV-1 and HIV-2 proviral DNA polymerase chain reaction (PCR). To evaluate the HIV-2 cellular proviral DNA loads, a quantitative competitive PCR (QC-PCR) was developed using nested primers to amplify the gag region of HIV-2. This assay used an internal competitor generated by inserting 25 bp in the first-round PCR target sequence. T-lymphocyte subset counts were estimated by flow cytometry for both HIV-2 monotypic and dually infected persons. RESULTS: 35 HIV-2-infected and 33 dually seroreactive samples were evaluated in this study. The CD4+ lymphocyte counts were similar in both groups, with mean values of 449 +/- 390 cells/mm3 for the HIV-2 monotypic infected persons and 476 +/- 308 cells/mm3 among the dually infected persons. However, the median proviral loads differed significantly, with those in the HIV-2 group ranging from 63.2 to 669.8 copies/10(5) CD4+ cells and demonstrating an inverse correlation with CD4+ lymphocyte count. The HIV dually infected persons showed less variation in viral load, ranging from 9.9 to 43.3 copies/10(5) CD4+ cells. Among the HIV dually infected persons, low HIV-2 proviral load was correlated with low CD4+ lymphocyte counts. CONCLUSIONS: The HIV-2 proviral loads in HIV dually infected persons were significantly lower than those in HIV-2 monotypically infected individuals (P < .0001), despite comparable CD4+ lymphocyte counts. These results suggest that different HIV-2 proviral dynamics prevail in HIV dual infection.     

Markers in HIV associated tuberculosis in Kenya

Tuberculosis is one of the most frequent opportunistic infections in HIV-infected patients in developing countries. In some instances, manifestations of pulmonary tuberculosis precede all other HIV related signs and symptoms because of the high virulence of M. tuberculosis. In order to characterise the interaction between these two pathogens, clinical and immunological parameters in pulmonary tuberculosis patients with and without HIV infection were compared. Amongst newly diagnosed pulmonary tuberculosis patients the association of some of these changes with the clinical outcome were evaluated. Of these, 44% were co-infected with HIV. Pulmonary tuberculosis patients with HIV-1 presented more frequently with lymphadenopathy and diarrhoea than those without HIV-1. Peripheral blood CD4+ counts were significantly lower in patients with pulmonary tuberculosis with HIV-1 than those with pulmonary tuberculosis alone, P= 0.0292. Low CD4+ lymphocyte counts, lymphadenopathy and BCG scar absence could serve as indicators of HIV-1 infection in pulmonary tuberculosis (PTB) patients.     

Impaired natural killer cell‐induced antibody‐dependent cell‐mediated cytotoxicity is associated with human immunodeficiency virus‐1 disease progression

This study evaluates the correlation between natural killer (NK) cell function and human immunodeficiency virus (HIV)-1 disease progression in 133 untreated HIV-1 positive Chinese subjects, including 41 former plasma donors (FPDs) and 92 men who have sex with men, and 35 HIV-negative controls. Flow cytometry was used to determine the abundance of NK cell subsets, the expression levels of receptor species, human leucocyte antigen (HLA) genotyping and the antibody-dependent cell-mediated cytotoxicity (ADCC) responses of NK cells. We observed a decreased expression of CD56^dimCD16⁺ NK cell subsets and an increased expression of CD56⁻CD16⁺ with HIV-1 infection. As well, the expression of activating and inhibitory receptors increased significantly in NK cells, but CD16 receptor levels and the NKG2A/NKG2C ratio were down-regulated with HIV-1 infection. ADCC responses were higher in elite controllers than in all other groups, and were correlated inversely with HIV-1 viral load but correlated positively with CD4 count only in FPDs. Furthermore, individuals infected for < 1 year have lower ADCC responses than those infected for > 1 year. We also observed a negative association between ADCC responses and viral load in those who carry the HLA-A*30/B*13/Cw*06 haplotype. The positive correlation between CD16 expression and ADCC responses and a negative correlation trend between CD158a and ADCC responses were also observed (P = 0·058). Our results showed that the ADCC response is associated with patients'' disease status, receptor expression levels, infection time and specific HLA alleles, which indicates that ADCC may offer protective effects against HIV-1 infection.     

Comparison of the clinical performance of the ECLusys HIV combi assay with the Lumipulse f and HISCL 2000-i HIV-1/2 ab screening assays

We compared the ECLusys HIV combi assay (ECL HIV Ag/Ab) to the Lumipulse Forte (LPf HIV 1/2 Ab) and HISCL (HIS HIV 1/2 Ab) assays. In a dilution sensitivity test using dilution panels of WHO HIV antibody international reference panel (HIV-1 Subtype A, B, C, E, HIV-1 Group O, HIV-2) and HIV-1/2 Ab CE marked material(HIV-1, HIV-2) parent specimens, the ECL assay enabled detection at a higher level of sensitivity than either the LPf assay or the HIS assay for all dilution panels. In an early detection test in the early phase of infection in which a BBI HIV seroconversion panel was used, the ECL assay enabled detection 7 days after initial blood sample collection, whereas the LPf and HIS assays enabled detection after 27 days. In a specificity test using high RF positive specimens (n=33), pregnancy specimens (n=35), cytomegalovirus antibody positive specimens (n=36), and high M protein positive specimens (n=21) that were confirmed negative for HIV-1/2 antibodies by the LPf assay, negative results were obtained for all specimens on both the ECL assay and the HIS assay. In a correlation test using routinely collected clinical specimens (n=121), including positive stock specimens, the ECL and HIS assays demonstrated the highest agreement rate 98.3%. The above results confirmed that the fourth-generation reagent ECL assay, which simultaneously detects both HIV-1/2 antibodies and p24 antigens, is both highly sensitive and specific, and is a suitable assay for use in routine testing.