ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo establish the prevalence of antibodies to HIV (anti-HIV) and associated risk factors among injecting drug users (IDU) in Togliatti City, Samara Oblast, Russian Federation.DesignAn unlinked anonymous cross-sectional community recruited survey with oral fluid sample collection.MethodsBetween September and October 2001, 426 IDU were recruited by trained fieldworkers. Participants completed an interviewer administered questionnaire, and oral fluid samples were tested for anti-HIV. Univariate and multivariate analyses compared potential risk factors for anti-HIV.ResultsAnti-HIV prevalence was 56% (234/418). Three-quarters of anti-HIV-positive IDU (74%) were unaware of their positive status. In an adjusted model, the odds of HIV infection were higher among IDU who had ever injected home-produced drugs, who reported injecting with used needles and syringes in the past 4 weeks, and who were living in one particular district of the city (Komsomolksii).ConclusionThe high prevalence of HIV, and a recent increase in HIV detected through routine screening tests since 2000, suggests that an explosive epidemic has occurred among IDU in Togliatti City. In the face of currently inadequate HIV prevention coverage among IDU, this has urgent implications for maximizing the distribution of sterile injecting equipment as well as for enhancing sexual risk reduction. Recognizing that it is likely that similar explosive epidemics are taking place in other Russian cities, we recommend community-wide HIV prevention coverage supported by city and state policies oriented to harm reduction.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundHIV-specific IgA is present in HIV-exposed uninfected individuals (EU) and neutralizes primary strains of HIV-1in vitro.ObjectivesTo analyse the antigenic correlates of HIV-1 neutralization using HIV epitopes and IgA from EU and HIV-seropositive individuals.MethodsSera from six heterosexual couples discordant for HIV serostatus, six age-matched HIV-infected subjects and six healthy controls (HC; as negative controls) were analysed. IgA binding on HIV Env recombinant proteins was assayed. Serum IgA was affinity purified on specific Env peptides and tested in HIV neutralization using resting and activated peripheral blood mononuclear cells as target. Monoclonal antibody 2F5 was used as neutralizing positive control. BALB/c mice were immunized with specific gp41 peptide and anti-sera were tested in syncytia formation and in HIV viral replication.ResultsIgA of EU exclusively bound an epitope within gp41; this epitope was restricted to residues 582–588 (QARILAV) and corresponded to the leucine zip motif in the α-helical region. IgA of HIV-positive patients recognized epitopes expressed both in gp120 and gp41; these epitopes were in the N-terminal portion of the extramembrane region. Additionally, IgA of EU and antisera of QARILAV-immunized Balb/C mice blocked syncytia formation and viral replication. The dose-dependent neutralization behaviour of specific QARILAV-purified IgA was very similar to that obtained with monoclonal antibody 2F5.ConclusionThese results have important implications for the development of vaccines and therapeutical strategies against HIV infection.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundEfflux pumps situated on the plasma membrane, such as P-glycoprotein (Pgp) and the multidrug resistance related-protein 1 (MRP-1), have been shown to extrude HIV protease inhibitors from the cell. MRP-1 is present on many barrier sites throughout the body, such as the blood–brain and blood–testis interfaces and could reduce the concentration of protease inhibitors in these sanctuary sites for HIV-1 replication. Factors that modulate efflux pump functionin vivoare poorly defined.ObjectiveTo analyze the inhibitory potential of the anti-retroviral drugs indinavir, amprenavir, ritonavir, lamivudine or zidovudine to modulate MRP-1 function.MethodsEffect of anti-HIV drugs on the efflux pump activity of MRP-1 was evaluated in the presence of increasing concentrations of human plasma, using UMCC-1/VP cells which stably over-express MRP-1. MRP-1 activity was abrogated by probenecid. The potential of blocking MRP-1 function for an extended (3 day) time period, was also examined in MRP-1 over-expressing cells cultured with either probenecid or the anti-retroviral drugs and a cytotoxic compound (etoposide) that is transported by MRP-1.ResultsRitonavir inhibited the functional activity of MRP-1 similarly to probenecid, as demonstrated by re-sensitization of MRP-1 over-expressing cells to cytotoxic effects of etoposide. Inhibition by ritonavir was inversely related to the concentration of human plasma added to the cells (r2=0.89). Other anti-HIV drugs didn't affect the MRP-1 mediated efflux of etoposide.ConclusionsThese data may be exploitable to further improve sanctuary site concentrations of anti-HIV or anti-cancer drugs by using ritonavir as a lead compound to develop more potent MRP-1 inhibitors.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectivesTo examine the antigen specificities of HIV reservoir CD4 T cells in patients on prolonged and effective highly active antiretroviral therapy (HAART).DesignFive HIV-infected patients, who were highly adherent to antiretroviral treatment, were selected on the basis of long-term undetectable plasma viral RNA on unmodified HAART. To investigate the antigen specificities of infected memory CD4 T cells, we examined the capacity of recall antigens, including HIV antigens, to induce virus production by peripheral blood mononuclear cells (PBMC).MethodsTo quantify CD4 T cells infected by replication-competent virus, and to determine their antigen specificities, we used a limiting dilution-based culture assay. CD8 T cell-depleted PBMC at several cell densities were activated by using Tuberculin purified protein derivative, cytomegalovirus, or HIV-1 p24 with and without HIV-1 Nef.ResultsWe found that the pool of infected CD4 T cells includes HIV-specific cells with apparent frequencies between 5- and 100-fold higher than those of the common specificities for cytomegalovirus or Tuberculin.ConclusionOur findings suggest that a significant proportion of replication-competent HIV-infected CD4 T cells in these patients are memory cells directed against HIV determinants. This may provide a rationale for the therapeutic use of recombinant HIV antigens to reduce the pool of HIV-reservoir cells.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectivesAs spontaneous anti-HIV-1 antibody and IgG secretion by peripheral blood mononuclear cells (PBMC) reflect immune system activation by HIV-1 antigens, we evaluated the impact of antiretroviral therapies on HIV-1 specific and non-specific B cell responses.MethodsAnti-HIV-1 antibody and non-specific IgG were measured by ELISA in supernatants of PBMC cultured during 7 day from 30 patients initiating an antiretroviral therapy at baseline, 8, 16, 24, 36 and 48 weeks.ResultsAn early and sustained fall in plasma viral load to below the detection limit (20 copies/ml) was observed in 17 sustained responder patients (SR), whereas HIV-1 RNA remained detectable in 13 others incomplete responders. In both groups, HIV-1 specific antibody secretion decreased significantly in parallel with plasma viral load and polyclonal immunoglobulin production became similar to that of PBMC controls. However, HIV-1 specific antibody production became negative in only six SR, exhibiting a greater increase of CD4 T-cell counts and higher levels of the spontaneous HIV-1 specific IgA secretion at baseline than the other SR.ConclusionsAntiretroviral therapy induced a rapid and dramatic decrease of spontaneous HIV-1 specific and non-specific B cell responses. These results pointed out that HIV-1 specific antibody secretion persisted in 11 out of 17 SR patients, suggesting persistent immune system activation by residual HIV-1 antigens.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundThe objective was to analyse which baseline factors could predict a favourable outcome after structured therapy interruption (STI).MethodsData of three Spanish pilot studies of STI in early stage chronic HIV-1-infected patients were analysed. A set of 37 variables at baseline was used. Plasma and tonsillar tissue viral load (VL), lymphocyte immunophenotyping and proliferative responses (LPR) to mitogens and specific antigens, and HIV-1 specific cytotoxic T lymphocyte responses were assessed at baseline. Response was defined as a VL set-point after 6 months off antiretroviral therapy after the last interruption of < 5000 copies/ml and 0.5 log10below baseline PVL before any antiretroviral therapy.ResultsAfter STI, the 44 patients were classified as follows: 18 (41%) as responders, 26 (59%) as non-responders. In the univariate analysis patients who responded had a significantly lower baseline level of CD4CD38 (P= 0.0068) and naive CD4 T cells (P= 0.03), and a higher level of memory CD4 T cells (P= 0.03) and proliferative response to tetanus toxoid (TT) (P= 0.01) and HIV-1 p24 (P= 0.03) than non-responders. A model incorporating five qualitative variables transformed according to the median value (CD4CD38, CD4 naive and memory T cells and stimulation index to TT and HIV-1 p24) at baseline could classify 97% of patients correctly (P= 0.0001).ConclusionsA level of memory CD4 T cells and proliferative response to recall antigens above the median may predict a good response to STI, suggesting that preserved memory response in CD4 T cells is important factor.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundControl of HIV replication can be observed in highly active antiretroviral therapy (HAART)-treated and, occasionally, in HAART-naive patients. The immunological correlates of these situations were examined in a longitudinal study.DesignA prospective study. Immunovirological analyses in 16 chronically HIV-infected, HAART-naive patients (time 0) who started HAART. Fifteen patients (short-term HAART) were re-evaluated after 24 months (time 1). Results were compared with those of 30 patients who received HAART for more than 12 months before the study period (long-term HAART) and were analysed at the same timepoints. Fifteen patients who were antiviral therapy naive (naive) at both timepoints were also studied.ResultsOver a 24-month period CD4 and CD8 cell counts and viraemia remained unchanged in naive and long-term HAART patients; CD4 cell counts increased and viraemia diminished in short-term HAART individuals. Antigen-stimulated proliferation was unmodified in naive and short-term HAART patients, but improved in long-term HAART individuals. Gp160-stimulated IL-2 and IFN-γ production was augmented in long-term HAART patients and marginally modified in other patients. IL-7 production was unmodified in naive individuals, augmented in short-term HAART patients, and diminished in long-term HAART patients. Chemokine production was similar in all patients. Naive patients showed the highest CD8 cell counts at both timepoints.ConclusionHAART has a major impact on the outcome of HIV infection, even if functional immune modulation in HAART-treated patients is evident only after long periods of therapy. Low but detectable HIV replication in HAART-naive patients with preserved immune functions might not be associated with CD4 cell reduction, functional immune defects, or changes in viraemia.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo assess and compare the mortality rates of patients with HIV-1, HIV-2 or both infections (HIV-D) in the same population.DesignClinic-based cohort study.MethodsHIV-seropositive patients aged 15 years and older who attended the Medical Research Council clinics in Fajara between May 1986 and September 1997 were recruited. Clinical assessment using the Karnofsky score, CDC cell staging, WHO staging, and CD4 cell counts was performed at baseline. Patients attended clinic every 3 months; if they did not attend, they were visited at home by field workers to ascertain survival status. No patient was on antiretroviral therapy during the study period.ResultsData from 1519 HIV-positive adult patients were analysed. A total of 746 patients had HIV-1, 666 HIV-2, and 107 patients had HIV-D. A total of 828 patients (55%) died, and 161 (11%) were lost to follow-up. The median follow-up was 12 months (range 0–128). CD4 cell counts were available for 894 patients. Compared with HIV-1, the adjusted hazards ratio for mortality in the CD4 cell count category 500 cells/μl or greater was 0.50 for HIV-2 (95% CI 0.28–0.88) and 1.27 (95% CI 0.51–3.7) for HIV-D. Among those with CD4 cell counts less than 500 cells/μl the mortality rates in HIV-2 and HIV-D were similar to those in HIV-1.DiscussionHIV-2-infected patients with CD4 cell counts of 500 cells/μl and greater had a significantly lower mortality rate than HIV-1-infected patients. HIV-2-infected patients with advanced disease had the same poor prognosis as patients with HIV-1. Dually infected patients had mortality rates similar to HIV-1.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID