Cristina Cellerai

Swiss Institute of Bioinformatics, Lausanne, Vaud, Switzerland

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Publications (26)150.83 Total impact

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    ABSTRACT: Routine screening of patients at risk of hepatitis C virus (HCV) infection has become a priority given recent improvements in therapeutic options and the asymptomatic nature of most chronic infections. The aim of this study was to evaluate the performance of the Elecsys® Anti-HCV II assay, a new qualitative antibody immunoassay, compared with currently available assays, and assess its suitability for routine diagnostic testing. The sensitivity of the Elecsys® Anti-HCV II, ARCHITECT® Anti-HCV, AxSYM® HCV 3.0, PRISM® HCV, Vitros® ECi Anti-HCV, Elecsys® Anti-HCV, and ADVIA Centaur® HCV assays was compared using commercially available seroconversion panels and samples from patients known to be HCV positive and infected with HCV genotypes 1-6. Specificity was investigated using samples from blood donors, unselected hospitalized patients, and patients with potential cross-reacting factors or from high-risk groups. The Elecsys® Anti-HCV II assay detected more positive bleeds than the comparator assays, was more sensitive in recognizing early HCV infection, and correctly identified all 765 samples known to be HCV positive, regardless of genotype. The overall specificity of the Elecsys(®) Anti-HCV II assay was 99.84% (n = 6,850) using blood donor samples, 99.66% (n = 3,922) using samples from unselected hospitalized patients, and 99.66% (n = 2,397) using samples from patients with potentially cross-reacting factors or from high-risk groups. The specificity of the Elecsys® Anti-HCV II assay was superior or equal to the comparator assays. In conclusion, the Elecsys® Anti-HCV II assay is a sensitive and specific assay suitable for routine use in the reliable detection of anti-HCV antibodies. J. Med. Virol. 85:1362-1368, 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 08/2013; 85(8):1362-8. · 2.37 Impact Factor
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    ABSTRACT: The success of combination antiretroviral therapy is limited by the evolutionary escape dynamics of HIV-1. We used Isotonic Conjunctive Bayesian Networks (I-CBNs), a class of probabilistic graphical models, to describe this process. We employed partial order constraints among viral resistance mutations, which give rise to a limited set of mutational pathways, and we modeled phenotypic drug resistance as monotonically increasing along any escape pathway. Using this model, the individualized genetic barrier (IGB) to each drug is derived as the probability of the virus not acquiring additional mutations that confer resistance. Drug-specific IGBs were combined to obtain the IGB to an entire regimen, which quantifies the virus' genetic potential for developing drug resistance under combination therapy. The IGB was tested as a predictor of therapeutic outcome using between 2,185 and 2,631 treatment change episodes of subtype B infected patients from the Swiss HIV Cohort Study Database, a large observational cohort. Using logistic regression, significant univariate predictors included most of the 18 drugs and single-drug IGBs, the IGB to the entire regimen, the expert rules-based genotypic susceptibility score (GSS), several individual mutations, and the peak viral load before treatment change. In the multivariate analysis, the only genotype-derived variables that remained significantly associated with virological success were GSS and, with 10-fold stronger association, IGB to regimen. When predicting suppression of viral load below 400 cps/ml, IGB outperformed GSS and also improved GSS-containing predictors significantly, but the difference was not significant for suppression below 50 cps/ml. Thus, the IGB to regimen is a novel data-derived predictor of treatment outcome that has potential to improve the interpretation of genotypic drug resistance tests.
    PLoS Computational Biology 08/2013; 9(8):3203-. · 4.87 Impact Factor
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    ABSTRACT: The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood. We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection (PHI) or chronic (progressive and non-progressive) infection. The functional avidity of HIV-specific CD8 T cells was not different between patients with progressive and non-progressive chronic infection. However, it was significantly lower in PHI patients at the time of diagnosis of acute infection and after control of virus replication following one year of successful antiretroviral therapy. High-avidity HIV-specific CD8 T cells expressed lower levels of CD27 and CD28 and were enriched in cells with an exhausted phenotype, i.e. co-expressing PD-1/2B4/CD160. Of note, a significant increase in the functional avidity of HIV-specific CD8 T cells occurred in early-treated PHI patients experiencing a virus rebound after spontaneous treatment interruption. This increase in functional avidity was associated with the accumulation of PD-1/2B4/CD160 positive cells, loss of polyfunctionality and increased TCR renewal. The increased TCR renewal may provide the mechanistic basis for the generation of high-avidity HIV-specific CD8 T cells. These results provide insights on the relationships between functional avidity, viremia, T-cell exhaustion and TCR renewal of antiviral CD8 T cell responses.
    PLoS Pathogens 07/2013; 9(7):e1003423. · 8.14 Impact Factor
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    ABSTRACT: BACKGROUND AND AIM: Recently, genetic variations in MICA (lead single nucleotide polymorphism [SNP] rs2596542) were identified by a genome-wide association study (GWAS) to be associated with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in Japanese patients. In the present study, we sought to determine whether this SNP is predictive for HCC development in the Caucasian population as well. METHODS: An extended region around rs2596542 was genotyped in 1924 HCV-infected patients from the Swiss Hepatitis C Cohort Study (SCCS). Pair-wise correlation between key SNPs was calculated both in the Japanese- and the European populations (HapMap3: CEU and JPT). RESULTS: To our surprise, the minor allele A of rs2596542 in proximity of MICA appeared to have a protective impact on HCC development in Caucasians, which represents an inverse association as compared to the one observed in the Japanese population. Detailed fine-mapping analyses revealed a new SNP in HCP5 (rs2244546) upstream of MICA as strong predictor for HCV-related HCC in the SCCS (univariable P=0.027; multivariable P=0.0002, odds ratio=3.96, 95% confidence interval=1.90-8.27). This newly identified SNP had a similarly directed effect on HCC in both Caucasian and Japanese populations, suggesting that rs2244546 may better tag a putative true variant than the originally identified SNPs. CONCLUSION: Our data confirms the MICA / HCP5 region as susceptibility locus for HCV-related HCC and identifies rs2244546 in HCP5 as a novel tagging SNP. In addition, our data exemplify the need for conducting meta-analyses of cohorts of different ethnicities in order to fine-map GWAS signals.
    Journal of Hepatology 05/2013; · 9.86 Impact Factor
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    ABSTRACT: Education and diagnostic tests capable of early detection represent our most effective means of preventing transmission of human immunodeficiency virus (HIV). The importance of early detection is underlined by studies demonstrating increased life expectancy following early initiation of antiviral treatment. The Elecsys(®) HIV combi PT assay is a fourth-generation antigen-antibody combination assay developed to allow earlier detection of seroconversion, and to have increased sensitivity and improved specificity. We aimed to determine how early the assay could detect infection compared with existing assays; whether all HIV variants could be detected; and the assay's specificity using samples from blood donors, routine specimens, and patients with potential cross-reacting factors. Samples were identified as positive by the Elecsys(®) assay 4.9 days after a positive polymerase chain reaction result (as determined by the panel supplier), which was earlier than the 5.3-7.1 days observed with comparators. The analytical sensitivity of the Elecsys(®) HIV combi PT assay for the HIV-1 p24 antigen was 1.05 IU/mL, which compares favorably with the comparator assays. In addition, the Elecsys(®) assay identified all screened HIV subtypes and displayed greater sensitivity to HIV-2 homologous antigen and antibodies to HIV-1 E and O and HIV-2 than the other assays. Overall, the specificity of the Elecsys(®) assay was 99.88 % using samples from blood donors and 99.81 % when analyzing unselected samples. Potential cross-reacting factors did not interfere with assay performance. The Elecsys(®) HIV combi PT assay is a sensitive and specific assay that has been granted the CE mark according to Directive 2009/886/EC.
    Medical Microbiology and Immunology 06/2012; · 3.55 Impact Factor
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    ABSTRACT: Contact structure is believed to have a large impact on epidemic spreading and consequently using networks to model such contact structure continues to gain interest in epidemiology. However, detailed knowledge of the exact contact structure underlying real epidemics is limited. Here we address the question whether the structure of the contact network leaves a detectable genetic fingerprint in the pathogen population. To this end we compare phylogenies generated by disease outbreaks in simulated populations with different types of contact networks. We find that the shape of these phylogenies strongly depends on contact structure. In particular, measures of tree imbalance allow us to quantify to what extent the contact structure underlying an epidemic deviates from a null model contact network and illustrate this in the case of random mixing. Using a phylogeny from the Swiss HIV epidemic, we show that this epidemic has a significantly more unbalanced tree than would be expected from random mixing.
    PLoS Computational Biology 03/2012; 8(3):e1002413. · 4.87 Impact Factor
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    ABSTRACT: We hypothesized that polymorphic mutations exist that are associated with the emergence of the multinucleoside resistance mutations (MNR), 69 insertion and Q151M. The Swiss HIV Cohort Study was screened, and the frequencies of polymorphic mutations in HIV-1 (subtype B) were compared between patients detected with the 69 insertion (n = 17), Q151M (n = 29), ≥2 thymidine analogue mutations (TAM) 1 (n = 400) or ≥2 TAM 2 (n = 249). Logistic regressions adjusted for the antiretroviral treatment history were performed to analyze the association of the polymorphic mutations with MNR. The 69 insertion and TAM 1 were strongly associated and occurred in 94.1% (16 of 17) together. The 69 insertion seemed to emerge as a consequence of the TAM 1 pathway (median years until detection: 6.8 compared with 4.4 for ≥2 TAM 1, P Wilcoxon = 0.009). Frequencies of 8 polymorphic mutations (K43E, V60I, S68G, S162C, T165I, I202V, R211K, F214L) were significantly different between groups. Logistic regression showed that F214L and V60I were associated with the emergence of Q151M/TAM 2 opposed to 69 insertion/TAM 1. S68G, T165I, and I202V were associated with Q151M instead of TAM 2. Besides antiretroviral therapy, polymorphic mutations may contribute to the emergence of specific MNR mutations.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2012; 59(2):105-12. · 4.65 Impact Factor
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    ABSTRACT: To determine 1) HIV testing practices in a 1400-bed university hospital where local HIV prevalence is 0.4% and 2) the effect on testing practices of national HIV testing guidelines, revised in March 2010, recommending Physician-Initiated Counselling and Testing (PICT). Using 2 hospital databases, we determined the number of HIV tests performed by selected clinical services, and the number of patients tested as a percentage of the number seen per service ('testing rate'). To explore the effect of the revised national guidelines, we examined testing rates for two years pre- and two years post-PICT guideline publication. Combining the clinical services, 253,178 patients were seen and 9,183 tests were performed (of which 80 tested positive, 0.9%) in the four-year study period. The emergency department (ED) performed the second highest number of tests, but had the lowest testing rates (0.9-1.1%). Of inpatient services, neurology and psychiatry had higher testing rates than internal medicine (19.7% and 9.6% versus 8%, respectively). There was no significant increase in testing rates, either globally or in the majority of the clinical services examined, and no increase in new HIV diagnoses post-PICT recommendations. Using a simple two-database tool, we observe no global improvement in HIV testing rates in our hospital following new national guidelines but do identify services where testing practices merit improvement. This study may show the limit of PICT strategies based on physician risk assessment, compared to the opt-out approach.
    PLoS ONE 01/2012; 7(6):e39299. · 3.53 Impact Factor
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    ABSTRACT: Minor protease inhibitor (PI) mutations often exist as polymorphisms in HIV-1 sequences from treatment-naïve patients. Previous studies showed that their presence impairs the antiretroviral treatment (ART) response. Evaluating these findings in a larger cohort is essential. To study the impact of minor PI mutations on time to viral suppression and time to virological failure, we included patients from the Swiss HIV Cohort Study infected with HIV-1 subtype B who started first-line ART with a PI and two nucleoside reverse transcriptase inhibitors. Cox regression models were performed to compare the outcomes among patients with 0 and ≥ 1 minor PI mutation. Models were adjusted for baseline HIV-1 RNA, CD4 cell count, sex, transmission category, age, ethnicity, year of ART start, the presence of nucleoside reverse transcriptase inhibitor mutations, and stratified for the administered PIs. We included 1199 patients of whom 944 (78.7%) received a boosted PI. Minor PI mutations associated with the administered PI were common: 41.7%, 16.1%, 4.7% and 1.9% had 1, 2, 3 or ≥ 4 mutations, respectively. The time to viral suppression was similar between patients with 0 (reference) and ≥ 1 minor PI mutation (multivariable hazard ratio (HR): 1.1 [95% confidence interval (CI): 1.0-1.3], P = .196). The time to virological failure was also similar (multivariable HR:.9 [95% CI:.5-1.6], P = .765). In addition, the impact of each single minor PI mutation was analyzed separately: none was significantly associated with the treatment outcome. The presence of minor PI mutations at baseline has no effect on the therapy outcome in HIV infected individuals.
    PLoS ONE 01/2012; 7(6):e37983. · 3.53 Impact Factor
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    ABSTRACT: Estimates of drug resistance incidence to modern first-line combination antiretroviral therapies against human immunodeficiency virus (HIV) type 1 are complicated by limited availability of genotypic drug resistance tests (GRTs) and uncertain timing of resistance emergence. Five first-line combinations were studied (all paired with lamivudine or emtricitabine): efavirenz (EFV) plus zidovudine (AZT) (n = 524); EFV plus tenofovir (TDF) (n = 615); lopinavir (LPV) plus AZT (n = 573); LPV plus TDF (n = 301); and ritonavir-boosted atazanavir (ATZ/r) plus TDF (n = 250). Virological treatment outcomes were classified into 3 risk strata for emergence of resistance, based on whether undetectable HIV RNA levels were maintained during therapy and, if not, whether viral loads were >500 copies/mL during treatment. Probabilities for presence of resistance mutations were estimated from GRTs (n = 2876) according to risk stratum and therapy received at time of testing. On the basis of these data, events of resistance emergence were imputed for each individual and were assessed using survival analysis. Imputation was repeated 100 times, and results were summarized by median values (2.5th-97.5th percentile range). Six years after treatment initiation, EFV plus AZT showed the highest cumulative resistance incidence (16%) of all regimens (<11%). Confounder-adjusted Cox regression confirmed that first-line EFV plus AZT (reference) was associated with a higher median hazard for resistance emergence, compared with other treatments: EFV plus TDF (hazard ratio [HR], 0.57; range, 0.42-0.76), LPV plus AZT (HR, 0.63; range, 0.45-0.89), LPV plus TDF (HR, 0.55; range, 0.33-0.83), ATZ/r plus TDF (HR, 0.43; range, 0.17-0.83). Two-thirds of resistance events were associated with detectable HIV RNA level ≤500 copies/mL during treatment, and only one-third with virological failure (HIV RNA level, >500 copies/mL). The inclusion of TDF instead of AZT and ATZ/r was correlated with lower rates of resistance emergence, most likely because of improved tolerability and pharmacokinetics resulting from a once-daily dosage.
    Clinical Infectious Diseases 11/2011; 54(1):131-40. · 9.37 Impact Factor
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    ABSTRACT: HIV-1 replicative capacity (RC) provides a measure of within-host fitness and is determined in the context of phenotypic drug resistance testing. However it is unclear how these in-vitro measurements relate to in-vivo processes. Here we assess RCs in a clinical setting by combining a previously published machine-learning tool, which predicts RC values from partial pol sequences with genotypic and clinical data from the Swiss HIV Cohort Study. The machine-learning tool is based on a training set consisting of 65000 RC measurements paired with their corresponding partial pol sequences. We find that predicted RC values (pRCs) correlate significantly with the virus load measured in 2073 infected but drug naïve individuals. Furthermore, we find that, for 53 pairs of sequences, each pair sampled in the same infected individual, the pRC was significantly higher for the sequence sampled later in the infection and that the increase in pRC was also significantly correlated with the increase in plasma viral load and with the length of the time-interval between the sampling points. These findings indicate that selection within a patient favors the evolution of higher replicative capacities and that these in-vitro fitness measures are indicative of in-vivo HIV virus load.
    PLoS Pathogens 11/2011; 7(11):e1002321. · 8.14 Impact Factor
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    ABSTRACT: Intervention with antiretroviral treatment (ART) and control of viral replication at the time of HIV-1 seroconversion may curtail cumulative immunological damage. We have therefore hypothesized that ART maintenance over a very prolonged period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 long-term non-progressors (LTNPs). We have investigated a cohort of 20 HIV-1 seroconverters on long-term ART (LTTS) and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-associated HIV-1 RNA and DNA, respectively, were demonstrated to be similarly low in both cohorts. These two virologically matched cohorts were then comprehensively analysed by polychromatic flow cytometry for HIV-1-specific CD4(+) and CD8(+) T-cell functional profile in terms of cytokine production and cytotoxic capacity using IFN-γ, IL-2, TNF-α production and perforin expression, respectively. Comparable levels of highly polyfunctional HIV-1-specific CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on HIV-1-specific CD8(+) T-cells, consistent with a polyfunctional/non-cytotoxic profile in a context of low viral burden. Our results indicate that prolonged ART initiated at the time of HIV-1 seroconversion is associated with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of early treatment initiation and paving the way for further interventions to promote virological control after treatment interruption.
    PLoS ONE 01/2011; 6(4):e18164. · 3.53 Impact Factor
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    ABSTRACT: Cytotoxicity and proliferation capacity are key functions of antiviral CD8 T cells. In the present study, we investigated a series of markers to define these functions in virus-specific CD8 T cells. We provide evidence that there is a lack of coexpression of perforin and CD127 in human CD8 T cells. CD127 expression on virus-specific CD8 T cells correlated positively with proliferation capacity and negatively with perforin expression and cytotoxicity. Influenza virus-, cytomegalovirus-, and Epstein-Barr virus/human immunodeficiency virus type 1-specific CD8 T cells were predominantly composed of CD127(+) perforin(-)/CD127(-) perforin(+), and CD127(-)/perforin(-) CD8 T cells, respectively. CD127(-)/perforin(-) and CD127(-)/perforin(+) cells expressed significantly more PD-1 and CD57, respectively. Consistently, intracellular cytokine (gamma interferon, tumor necrosis factor alpha, and interleukin-2 [IL-2]) responses combined to perforin detection confirmed that virus-specific CD8 T cells were mostly composed of either perforin(+)/IL-2(-) or perforin(-)/IL-2(+) cells. In addition, perforin expression and IL-2 secretion were negatively correlated in virus-specific CD8 T cells (P < 0.01). As previously shown for perforin, changes in antigen exposure modulated also CD127 expression. Based on the above results, proliferating (CD127(+)/IL-2-secreting) and cytotoxic (perforin(+)) CD8 T cells were contained within phenotypically distinct T-cell populations at different stages of activation or differentiation and showed different levels of exhaustion and senescence. Furthermore, the composition of proliferating and cytotoxic CD8 T cells for a given antiviral CD8 T-cell population appeared to be influenced by antigen exposure. These results advance our understanding of the relationship between cytotoxicity, proliferation capacity, the levels of senescence and exhaustion, and antigen exposure of antiviral memory CD8 T cells.
    Journal of Virology 04/2010; 84(8):3868-78. · 5.08 Impact Factor
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    ABSTRACT: Cytotoxic CD8 T cells exert their antiviral and antitumor activity primarily through the secretion of cytotoxic granules. Degranulation activity and cytotoxic granules (perforin plus granzymes) generally define CD8 T cells with cytotoxic function. In this study, we have investigated the expression of granzyme K (GrmK) in comparison to that of GrmA, GrmB, and perforin. The expression of the cytotoxic granules was assessed in virus-specific CD8 T cells specific to influenza virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus type 1 (HIV-1). We observed a dichotomy between GrmK and perforin expression in virus-specific CD8 T cells. The profile in influenza virus-specific CD8 T cells was perforin(-) GrmB(-) GrmA(+/-) GrmK(+); in CMV-specific cells, it was perforin(+) GrmB(+) GrmA(+) GrmK(-/+); and in EBV- and HIV-1-specific cells, it was perforin(-/+) GrmB(+) GrmA(+) GrmK(+). On the basis of the delineation of memory and effector CD8 T cells with CD45RA and CD127, the GrmK(+) profile was associated with early-stage memory CD8 T-cell differentiation, the perforin(+) GrmB(+) GrmA(+) profile with advanced-stage differentiation, and the GrmB(+) GrmA(+) Grmk(+) profile with intermediate-stage differentiation. Furthermore, perforin and GrmB but not GrmA and GrmK correlated with cytotoxic activity. Finally, changes in antigen exposure in vitro and in vivo during primary HIV-1 infection and vaccination modulated cytotoxic granule profiles. These results advance our understanding of the relationship between distinct profiles of cytotoxic granules in memory CD8 T cells and function, differentiation stage, and antigen exposure.
    Journal of Virology 02/2009; 83(7):2862-71. · 5.08 Impact Factor
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    Retrovirology 01/2009; · 5.66 Impact Factor
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    Retrovirology 01/2009; · 5.66 Impact Factor
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    ABSTRACT: The aim of this randomised controlled trial was to see if the addition of 4 mg/ml DNA-C priming given by the intramuscular route at weeks 0 and 4 to NYVAC-C at weeks 20 and 24, safely increased the proportion of participants with HIV-specific T-cell responses measured by the interferon (IFN)-gamma ELISpot assay at weeks 26 and/or 28 compared to NYVAC-C alone. Although 2 individuals discontinued after the first DNA-C due to adverse events (1 vaso-vagal; 1 transient, asymptomatic elevation in alanine transaminase), the vaccines were well tolerated. Three others failed to complete the regimen (1 changed her mind; 2 lost to follow-up). Of the 35 that completed the regimen 90% (18/20) in the DNA-C group had ELISpot responses compared to 33% (5/15) that received NYVAC-C alone (p=0.001). Responses were to envelope in the majority (21/23). Of the 9 individuals with responses to envelope and other peptides, 8 were in the DNA-C group. These promising results suggest that DNA-C was an effective priming agent, that merits further investigation.
    Vaccine 07/2008; 26(25):3162-74. · 3.49 Impact Factor
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    ABSTRACT: 15 pages, 8 figures.-- PMID: 18195071 [PubMed].-- PMCID: PMC2234371. The EuroVacc 02 phase I trial has evaluated the safety and immunogenicity of a prime-boost regimen comprising recombinant DNA and the poxvirus vector NYVAC, both expressing a common immunogen consisting of Env, Gag, Pol, and Nef polypeptide domain from human immunodeficiency virus (HIV)-1 clade C isolate, CN54. 40 volunteers were randomized to receive DNA C or nothing on day 0 and at week 4, followed by NYVAC C at weeks 20 and 24. The primary immunogenicity endpoints were measured at weeks 26 and 28 by the quantification of T cell responses using the interferon enzyme-linked immunospot assay. Our results indicate that the DNA C plus NYVAC C vaccine regimen was highly immunogenic, as indicated by the detection of T cell responses in 90% of vaccinees and was superior to responses induced by NYVAC C alone (33% of responders). The vaccine-induced T cell responses were (a) vigorous in the case of the env response (mean 480 spot-forming units/106 mononuclear cells at weeks 26/28), (b) polyfunctional for both CD4 and CD8 T cell responses, (c) broad (the average number of epitopes was 4.2 per responder), and (d) durable (T cell responses were present in 70% of vaccinees at week 72). The vaccine-induced T cell responses were strongest and most frequently directed against Env (91% of vaccines), but smaller responses against Gag-Pol-Nef were also observed in 48% of vaccinees. These results support the development of the poxvirus platform in the HIV vaccine field and the further clinical development of the DNA C plus NYVAC C vaccine regimen. The Ev02 clinical trial has been sponsored by the EuroVacc Foundation. The EuroVacc program has been supported by the European Commission fifth framework program under research grants QLK2-CT-1999-01321, QLK2-CT-2001-01316, and QLK2-CT-2002-01431. Peer reviewed
    Journal of Experimental Medicine 02/2008; · 13.21 Impact Factor
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    ABSTRACT: Treatment of primary HIV-1 infection may alter the natural history of HIV-1 infection and delay the need for chronic antiretroviral therapy; it may also be a public health measure. We discuss the results of therapeutic trials and cohort studies, the occurrence of transmitted drug resistance, and recent findings in terms of immunopathogenesis and decay of viral reservoirs. Events at the time of primary HIV-1 infection are understood to set the scene for persistence of immunologic damage and chronic immune activation, with a rapid viral onslaught primarily on memory CD4 T cells at mucosal effector sites. The initiation of antiretroviral therapy at primary HIV-1 infection has been associated with a high degree of undetectable viremia in compliant patients and substantial decay of reservoirs in peripheral blood. The degree of immune reconstitution at the gut mucosal level, however, does not appear to be comparable to that in peripheral blood. Recent insights into the long-term consequences of the early burst of HIV-1 replication - together with transmitted drug resistance, onward transmission, and the possibility of decay of viral reservoirs - are important steps in helping to design future therapeutic strategies in primary HIV-1 infection in an era of intense drug and vaccine development.
    Current opinion in HIV and AIDS 02/2008; 3(1):67-74. · 4.75 Impact Factor

Publication Stats

834 Citations
150.83 Total Impact Points

Institutions

  • 2013
    • Swiss Institute of Bioinformatics
      Lausanne, Vaud, Switzerland
  • 2011–2012
    • University of Zurich
      • Nationales Zentrum für Retroviren
      Zürich, ZH, Switzerland
  • 2005–2011
    • University Hospital of Lausanne
      • Service de neurologie
      Lausanne, Vaud, Switzerland
  • 2008
    • University College London
      • Molecular Immunology unit
      London, ENG, United Kingdom