***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Targeting canarypox (CP)-HIV vaccine to dendritic cells ( DCs ) elicits anti-HIV-1 immune responses in vitro . We conducted a phase I/II clinical trial to evaluate whether adding DC to a CP-HIV vaccine improved virologic control during analytic treatment interruption ( ATI ) in HIV-1-infected subjects . Twenty-nine subjects on suppressive antiretroviral therapy were r and omized to vaccination with autologous DCs infected with CP-HIV+keyhole limpet hemocyanin ( KLH ) ( arm A , n=14 ) or CP-HIV+KLH alone ( arm B , n=15 ) . The mean viral load ( VL ) setpoint during ATI did not differ between subjects in arms A and B. A higher percentage of subjects in the DC group had a VL setpoint < 5,000 c/mL during ATI ( 4/13 or 31 % in arm A compared with 0/13 in arm B , p=0.096 ) , but virologic control was transient . Subjects in arm A had a greater increase in KLH lymphoproliferative response than subjects in arm B ; however , summed ELISPOT responses to HIV-1 antigens did not differ by treatment arm . We conclude that a DC-CP-HIV vaccine is well-tolerated in HIV-1-infected patients , but does not lower VL setpoint during ATI compared with CP-HIV alone . New methods to enhance the immunogenicity and antiviral efficacy of DC-based vaccines for HIV-1 infection are needed BACKGROUND Immune priming before reversal of latency might be a component of a functional HIV cure . To assess this concept , we assessed if therapeutic HIV immunisation followed by latency reversal would affect measures of viral transcription , plasma viraemia , and reservoir size in patients with HIV on suppressive antiretroviral therapy . METHODS In this single-arm , phase 1B/2A trial , we recruited adults treated at the Department of Infectious Diseases , Aarhus University Hospital , Aarhus , Denmark ( aged ≥18 years ) with successfully treated HIV-1 with plasma RNA loads of less than 50 copies per mL for the previous year and CD4 counts of at least 500 cells per μL. Exclusion criteria included CD4 counts of less than 200 cells per μL within the past 2 years , active hepatitis B or C infections , and clinical ly significant cardiac disease , including QTc prolongation . Participants received six therapeutic intradermal HIV-1 immunisations with 12 mg/mL Vacc-4x and 0·6 mg/mL rhuGM-CSF over 12 weeks ( at 0 weeks , 1 week , 2 weeks , 3 weeks , 11 weeks , and 12 weeks ) before receiving 5 mg/m(2 ) intravenous romidepsin once a week for 3 weeks . This procedure was followed by analytical treatment interruption . Co primary outcomes were changes in copies of HIV-1 DNA ( total and integrated ) per million CD4 T cells and infectious units per million ( IUPM ) resting memory CD4 T cells established by viral outgrowth , assessed in all patients receiving at least one dose of active treatment with assessable data . We assessed total HIV-1 DNA at screening , before romidepsin treatment , and 6 weeks after romidepsin treatment . We assessed integrated viral DNA at baseline , before romidepsin treatment , and 8 weeks after romidepsin treatment . We assessed IUPM at screening , 2 weeks before romidepsin treatment , and 6 weeks after romidepsin treatment . This trial is registered at Clinical Trials.gov , number NCT02092116 . FINDINGS Between May 19 , 2014 , and Oct 8 , 2014 , we enrolled 20 individuals , of whom 17 completed all Vacc-4x and rhuGM-CSF administrations and romidepsin infusions . 16 of 17 had assessable total HIV-1 DNA , 15 of 17 had assessable integrated HIV-1 DNA , and six of 17 had assessable IUPM at baseline and at one or more timepoints after study treatment . Total HIV-1 DNA declined from screening to 6 weeks after romidepsin treatment ( mean reduction 39·7 % , 95 % CI -59·7 to -11·5 ; p=0·012 ) . The decrease in integrated HIV-1 DNA from baseline to 8 weeks after romidepsin treatment was not significant ( 19·2 % , -38·6 to 6·3 ; p=0·123 ) . Among the six assessable participants , the mean reduction in IUPM from screening to 6 weeks after romidepsin treatment was 38·0 % ( 95 % CI -67·0 to -8·0 ; p=0·019 ) . Of 141 adverse events , 134 ( 95 % ) were grade 1 and seven ( 5 % ) were grade 2 - 3 . INTERPRETATION This in-vivo combinatorial approach provides the first evidence for the feasibility of a combined shock and kill strategy , but also emphasises that further optimisation of this strategy is needed to achieve a sizeable effect on the latent reservoir that will translate into clinical ly measurable benefits for people living with HIV-1 . FUNDING Bionor Pharma , the Research Council of Norway , and SkatteFUNN Background : The genomic heterogeneity of HIV-1 impedes the ability of consensus sequences in vaccines to elicit effective antiviral immune responses . AGS-004 amplifies translation-competent RNA molecules encoding for Gag , Rev , Vpr , and Nef from the patient 's autologous virus and loads them into dendritic cells . Methods : This phase IIB , multicenter , 2:1 r and omized , double-blind , placebo-controlled study enrolled 54 HIV-1–infected patients on antiretroviral therapy with viral loads ( VLs ) < 50 copies per milliliter , current CD4 T-cell counts > 450 cells per cubic millimeter , and nadir counts > 200 cells per cubic millimeter , to receive intradermal injections of study product into the axillary lymph node region every 4 weeks . At week 16 , a 12-week analytical treatment interruption ( ATI ) was undertaken . Results : There was no difference in the end-of-ATI VL ( average of values from weeks 11 and 12 ) between the 2 arms of the study [ 4.39 ( 4.17 , 4.69 ) vs. 4.47 ( 3.76 , 4.64 ) log10 HIV-1 RNA ; P = 0.73 ] . Between arms , no change between pre – antiretroviral therapy VL and the end-of-ATI VL [ −0.06 ( 0.24 , −0.32 ) vs. −0.17 ( 0.17 , −0.32 ) log10 HIV-1 RNA ; P = 0.43 ] was observed . When interferon-&ggr ; , interleukin-2 , tumor necrosis factor & agr ; , CD107a , and granzyme b expressions were measured by multicolor flow cytometry , a greater percentage of AGS-004 than of placebo recipients had multifunctional cytotoxic T-lymphocyte responses induced in the CD28+/CD45RA-CD8 effector/memory T-cell population to dendritic cells electroporated with autologous antigens . Adverse events consisted of transient , mild ( grade 1 ) local injection site reactions . Conclusions : Despite the induction of HIV-specific effector/memory CD8 T-cell responses , no antiviral effect was seen after the administration of AGS-004 when compared with placebo OBJECTIVE This study aim ed to evaluate the effect of dendritic cell ( DC ) vaccination against HIV-1  on host gene expression profiles . DESIGN Longitudinal P BMC sample s were collected from participants of the DC-TRN trial for immunotherapy against HIV . Microarray-assisted gene expression profiling was performed to evaluate the effects of vaccination and subsequent interruption of antiretroviral therapy on host genome expression . Data from the DC-TRN trial were compared with results from other vaccination trials . METHODS We used Affymetrix GeneChips for microarray gene expression analysis . Data were analyzed by principal component analysis and differential gene expression was assessed using linear modeling . Gene ontology enrichment and gene set analysis were used to characterize differentially expressed genes . Transcriptome analysis included comparison with P BMC s obtained from  DC-vaccinated melanoma patients and of healthy individuals who received seasonal influenza vaccination .  RESULTS DC-TRN immunotherapy in HIV-infected individuals result ed in a major shift in the transcriptome . Longitudinal analysis demonstrated that changes in the transcriptome sustained also during interruption of antiretroviral therapy . After DC-vaccination , the transcriptome was enriched for cellular immunity associated genes that were also induced in healthy adults who received live attenuated influenza virus vaccination . These beneficial responses were accompanied by detrimental signals of general immune activation . CONCLUSIONS The DC-TRN induced changes in the transcriptome were profound , lasting , and consisted of both protective signals and signatures of inflammation and immune exhaustion , with a net result of decreased viral load , without clinical benefit . Thus transcriptome analysis provides useful information , dissecting both positive and negative effects , for the evaluation of safety and efficacy of immunotherapeutic strategies BACKGROUND We report the results of a phase I/II , open-label , single-arm clinical trial to evaluate the safety and anti-human immunodeficiency virus type 1 ( HIV-1 ) efficacy of an autologous dendritic cell (DC)-based HIV-1 vaccine loaded with autologous HIV-1-infected apoptotic cells . METHODS Antiretroviral therapy (ART)-naive individuals were enrolled , and viremia was suppressed by ART prior to delivery of 4 doses of DC-based vaccine . Participants underwent treatment interruption 6 weeks after the third vaccine dose . The plasma HIV-1 RNA level 12 weeks after treatment interruption was compared to the pre-ART ( ie , baseline ) level . RESULTS The vaccine was safe and well tolerated but did not prevent viral rebound during treatment interruption . Vaccination result ed in a modest but significant decrease in plasma viremia from the baseline level ( from 4.53 log10 copies/mL to 4.27 log10 copies/mL;P= .05 ) . Four of 10 participants had a > 0.70 log10 increase in the HIV-1 RNA load in plasma following vaccination , despite continuous ART . Single-molecule sequencing of HIV-1 RNA in plasma before and after vaccination revealed increases in G > A hypermutants in gag and pol after vaccination , which suggests cytolysis of infected cells . CONCLUSIONS A therapeutic HIV-1 vaccine based on DCs loaded with apoptotic bodies was safe and induced T-cell activation and cytolysis , including HIV-1-infected cells , in a subset of study participants . CLINICAL TRIALS REGISTRATION NCT00510497 A pilot study was carried out to assess the safety and antigen-presenting properties of allogeneic or autologous dendritic cells ( DCs ) in six HLA-A2 + , HIV-infected patients .  Allogeneic DCs obtained from the peripheral blood of HLA-identical , HIV-seronegative siblings were pulsed with recombinant HIV-1 MN gp160 or synthetic peptides corresponding to HLA-A2-restricted cytotoxic epitopes of envelope , Gag , and Pol proteins . The antigen-pulsed cells were infused intravenously six to nine times at monthly intervals and HIV-specific immune responses were monitored . One allogeneic DC recipient with a CD4 + T cell count of 460/mm3 showed increases in envelope-specific CTL- and lymphocyte-proliferative responses , as well as in IFN-gamma and IL-2 production . Another allogeneic DC recipient with a CD4 + T cell count of 434/mm3 also showed an increase in HIV envelope-specific lymphocyte-proliferative responses . A recipient of autologous DCs with a CD4 + T cell count of 730/mm3 showed an increase in peptide-specific lymphocyte-proliferative responses after three infusions . Three other allogeneic DC recipients with CD4 + T cell counts < 410/mm3 did not show increases in their HIV-specific immune responses . No clinical ly significant adverse effects were noted in this study and CD4 + T cell numbers and plasma HIV-1 RNA detected by RT-PCR of all six patients were stable during the study period . Thus , both allogeneic and autologous DC infusions were well tolerated and in patients with normal or near normal CD4 + T cell counts administration of these antigen-pulsed cells enhanced the immune response to HIV . However , since no effect on viral load was observed there was no evidence that this approach provided clinical benefit Efforts aim ed at restoring robust immune responses limiting human immunodeficiency virus (HIV)-1 replication therapeutically are warranted . We report that vaccination with dendritic cells generated ex vivo and loaded with HIV lipopeptides in patients ( n = 19 ) on antiretroviral therapy was well tolerated and immunogenic . Vaccination increased : ( i ) the 
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Protocol s differed according to antigen choice , DC culture method , and doses , although multivariate analysis did not show an influence of any of them on overall success rate .
The DC-based vaccines elicited at least some immunogenicity , that was sometimes associated with plasmatic viral load transient control .
Although the vaccines did not work as expected , they are proof of concept that immune responses can be boosted against HIV-1 .