Replication Capacity and Susceptibility to Telaprevir of the T54S Resistant Variant is Modulated by Others Hepatitis C Virus NS3 Mutations
; BONTEMS, Sébastien ; et al
Poster (2013)Detailed reference viewed: 4 (0 ULg)
Prevalence of HIV and HCV infections in two populations of Malian women and serological assays performances
; VAIRA, Dolorès ; Gothot, André et al
in World Journal of Hepatology (2012)Detailed reference viewed: 12 (5 ULg)
HCV screening in African (Malian) women : relevancy of the HCV NS3 epitope
; VAIRA, Dolorès ; GOTHOT, André et al
Poster (2012)Detailed reference viewed: 5 (3 ULg)
Study of HCV and HIV infections in Mali: Comparative Epidemiology and Risk Factors
; VAIRA, Dolorès ; GOTHOT, André et al
Poster (2012)Detailed reference viewed: 9 (4 ULg)
An Improved Protocol for Efficient Engraftment in NOD/ LTSZ-SCIDIL-2RcNULL Mice Allows HIV Replication and Development of Anti-HIV Immune Responses
; ; et al
in PLoS ONE (2012), 7(6), 38491
Cord blood hematopoietic progenitor cells (CB-HPCs) transplanted immunodeficient NOD/LtsZ-scidIL2Rcnull (NSG) and NOD/SCID/IL2Rcnull (NOG) mice need efficient human cell engraftment for long-term HIV-1 ... [more ▼]
Cord blood hematopoietic progenitor cells (CB-HPCs) transplanted immunodeficient NOD/LtsZ-scidIL2Rcnull (NSG) and NOD/SCID/IL2Rcnull (NOG) mice need efficient human cell engraftment for long-term HIV-1 replication studies. Total body irradiation (TBI) is a classical myeloablation regimen used to improve engraftment levels of human cells in these humanized mice. Some recent reports suggest the use of busulfan as a myeloablation regimen to transplant HPCs in neonatal and adult NSG mice. In the present study, we further ameliorated the busulfan myeloablation regimen with fresh CB-CD34+cell transplantation in 3–4 week old NSG mice. In this CB-CD34+transplanted NSG mice engraftment efficiency of human CD45+cell is over 90% in peripheral blood. Optimal engraftment promoted early and increased CD3+T cell levels, with better lymphoid tissue development and prolonged human cell chimerism over 300 days. These humanized NSG mice have shown long-lasting viremia after HIV-1JRCSF and HIV-1Bal inoculation through intravenous and rectal routes. We also saw a gradual decline of the CD4+T cell count, widespread immune activation, up-regulation of inflammation marker and microbial translocation after HIV-1 infection. Humanized NSG mice reconstituted according to our new protocol produced, moderate cellular and humoral immune responses to HIV-1 postinfection. We believe that NSG mice reconstituted according to our easy to use protocol will provide a better in vivo model for HIV-1 replication and anti-HIV-1 therapy trials. [less ▲]Detailed reference viewed: 19 (9 ULg)
Evolution over a 15 year period of the epidemiological profile of 2884 newly diagnosed HCV patients in Belgium.
LOLY, Jean ; GERARD, Christiane ; VAIRA, Dolorès et al
in Acta Gastro-Enterologica Belgica (2011, March), 74Detailed reference viewed: 25 (8 ULg)
Concordance between HIV-1 genotypic coreceptor tropism predictions based on plasma RNA and proviral DNA.
; ; et al
in HIV Medicine (2011), 12(9), 544-52
OBJECTIVE: The aim of the study was to evaluate the use of proviral DNA as a source of viral genetic material for genotypic coreceptor tropism testing (GTT). METHODS: GTT consisted of bulk V3 sequencing ... [more ▼]
OBJECTIVE: The aim of the study was to evaluate the use of proviral DNA as a source of viral genetic material for genotypic coreceptor tropism testing (GTT). METHODS: GTT consisted of bulk V3 sequencing followed by geno2pheno interpretation with the interpretative cut-off [false positive rate (FPR)] set at 5 and 10%. GTT was performed for 165 patients with a viral load of >500 HIV-1 RNA copies/mL on simultaneously collected plasma RNA and proviral DNA, and for 126 patients with a viral load of <500 copies/mL on current proviral DNA and pretreatment plasma RNA. Phenotypic tropism testing (PTT) results were available for 142 samples. RESULTS: In the simultaneous RNA/DNA comparison, concordance in prediction was 95.2% (at FPR 10%) and 96.4% (at FPR 5%). Six RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances were observed at an FPR of 10%, and six RNA-R5/DNA-X4 discordances were observed at an FPR of 5%. In the longitudinal RNA/DNA comparison, concordance was 88.1% (at FPR 10%) and 90.5% (at FPR 5%). Eight RNA-X4/DNA-R5 and seven RNA-R5/DNA-X4 discordances were seen at an FPR of 10%, and 10 RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances at an FPR of 5%. The overall concordance of RNA GTT with PTT was 82% (at FPR 10%) and 83% (at FPR 5%). The overall concordance of DNA GTT with PTT was 85% (at both 10 and 5% FPRs). CONCLUSIONS: GTT produced highly concordant tropism predictions for proviral DNA and plasma RNA. GTT on proviral DNA offers a promising approach for tropism prediction in clinical practice, particularly for the assessment of treated patients with low or suppressed viraemia. [less ▲]Detailed reference viewed: 10 (1 ULg)
Comparison of phenotypic and genotypic tropism determination in triple-class-experienced HIV patients eligible for maraviroc treatment.
; ; et al
in Journal of Antimicrobial Chemotherapy (2011), 66(2), 265-72
BACKGROUND: Determination of HIV-1 tropism is a pre-requisite to the use of CCR5 antagonists. This study evaluated the potential of population genotypic tropism tests (GTTs) in clinical practice, and the ... [more ▼]
BACKGROUND: Determination of HIV-1 tropism is a pre-requisite to the use of CCR5 antagonists. This study evaluated the potential of population genotypic tropism tests (GTTs) in clinical practice, and the correlation with phenotypic tropism tests (PTTs) in patients accessing routine HIV care. METHODS: Forty-nine consecutive plasma samples for which an original Trofile(TM) assay was performed were obtained from triple-class-experienced patients in need of a therapy change. Viral tropism was defined as the consensus of three or more tropism calls obtained from the combination of two independent population PTT assays (Trofile Biosciences, San Francisco, CA, USA, and Virco, Beerse, Belgium), population GTTs and GTTs based on ultra-deep sequencing. If no consensus was reached, a clonal PTT was performed in order to finalize the tropism call. This two-step approach allowed the definition of a reference tropism call. RESULTS: According to the reference tropism result, 35/49 samples were CCR5 tropic (R5) (patients eligible for maraviroc treatment) and 14/49 were assigned as non-R5 tropic. The non-R5 samples [patients not eligible for maraviroc treatment according to the FDA/European Medicines Agency (EMEA) label] group included both the CXCR4 (X4) samples and the dual and mixed CCR5/CXCR4 (R5/X4) samples. Compared with Trofile(TM) population PTTs, population GTTs showed a higher sensitivity (97%) and a higher negative predictive value (91%), but almost equal specificity and an equal positive predictive value. CONCLUSIONS: In line with recent reports from clinical trial data, our data support the use of population genotypic tropism testing as a tool for tropism determination before the start of maraviroc. [less ▲]Detailed reference viewed: 21 (5 ULg)
Hepatitis C of genotype 2: the role of medical invasive exams.
; GERARD, Christiane ; et al
in Acta gastro-enterologica Belgica (2011), 74(2), 277-80
BACKGROUND AND AIM: Hepatitis C virus genotype 2 is the third in order of frequency in Belgium. The aim of this study was to better define the genotype 2 carriers' epidemiology characteristics. METHODS ... [more ▼]
BACKGROUND AND AIM: Hepatitis C virus genotype 2 is the third in order of frequency in Belgium. The aim of this study was to better define the genotype 2 carriers' epidemiology characteristics. METHODS: In a database comprising 1726 viremic hepatitis C virus patient from the south part of Belgium, the files of 98 genotype 2 carriers were reviewed. RESULTS: There was a strong association between genotype 2 and the mode of transmission. The rate of contamination by invasive medical exams was very high (23%), and statistically different from the one of the others genotypes. Eligibility for antiviral therapies and the rate of sustained viral response were high. CONCLUSION: HCV genotype 2 was highly associated with transmission by invasive medical exams. [less ▲]Detailed reference viewed: 56 (10 ULg)
HIV-1 V3 envelope deep sequencing for clinical plasma specimens failing in phenotypic tropism assays.
; ; et al
in AIDS Research and Therapy (2010), 7
ABSTRACT : BACKGROUND : HIV-1 infected patients for whom standard gp160 phenotypic tropism testing failed are currently excluded from co-receptor antagonist treatment. To provide patients with maximal ... [more ▼]
ABSTRACT : BACKGROUND : HIV-1 infected patients for whom standard gp160 phenotypic tropism testing failed are currently excluded from co-receptor antagonist treatment. To provide patients with maximal treatment options, massively parallel sequencing of the envelope V3 domain, in combination with tropism prediction tools, was evaluated as an alternative tropism determination strategy. Plasma samples from twelve HIV-1 infected individuals with failing phenotyping results were available. The samples were submitted to massive parallel sequencing and to confirmatory recombinant phenotyping using a fraction of the gp120 domain. RESULTS : A cut-off for sequence reads interpretation of 5 to10 times the sequencing error rate (0.2%) was implemented. On average, each sample contained 7 different V3 haplotypes. V3 haplotypes were submitted to tropism prediction algorithms, and 4/14 samples returned with presence of a dual/mixed (D/M) tropic virus, respectively at 3%, 10%, 11%, and 95% of the viral quasispecies. V3 tropism prediction was confirmed by gp120 phenotyping, except for two out of 4 D/M predicted viruses (with 3 and 95%) which were phenotypically R5-tropic. In the first case, the result was discordant due to the limit of detection for the phenotyping technology, while in the latter case the prediction algorithms were not computing the viral tropism correctly. CONCLUSIONS : Although only demonstrated on a limited set of samples, the potential of the combined use of "deep sequencing + prediction algorithms" in cases where routine gp160 phenotype testing cannot be employed was illustrated. While good concordance was observed between gp120 phenotyping and prediction of R5-tropic virus, the results suggest that accurate prediction of X4-tropic virus would require further algorithm development. [less ▲]Detailed reference viewed: 37 (13 ULg)
Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: implications for treatment of latent infection.
; ; et al
in PLoS ONE (2009), 4(6), 6093
The persistence of transcriptionally silent but replication-competent HIV-1 reservoirs in Highly Active Anti-Retroviral Therapy (HAART)-treated infected individuals, represents a major hurdle to virus ... [more ▼]
The persistence of transcriptionally silent but replication-competent HIV-1 reservoirs in Highly Active Anti-Retroviral Therapy (HAART)-treated infected individuals, represents a major hurdle to virus eradication. Activation of HIV-1 gene expression in these cells together with an efficient HAART has been proposed as an adjuvant therapy aimed at decreasing the pool of latent viral reservoirs. Using the latently-infected U1 monocytic cell line and latently-infected J-Lat T-cell clones, we here demonstrated a strong synergistic activation of HIV-1 production by clinically used histone deacetylase inhibitors (HDACIs) combined with prostratin, a non-tumor-promoting nuclear factor (NF)- kappaB inducer. In J-Lat cells, we showed that this synergism was due, at least partially, to the synergistic recruitment of unresponsive cells into the expressing cell population. A combination of prostratin+HDACI synergistically activated the 5' Long Terminal Repeat (5'LTR) from HIV-1 Major group subtypes representing the most prevalent viral genetic forms, as shown by transient transfection reporter assays. Mechanistically, HDACIs increased prostratin-induced DNA-binding activity of nuclear NF-kappaB and degradation of cytoplasmic NF-kappaB inhibitor, IkappaBalpha . Moreover, the combined treatment prostratin+HDACI caused a more pronounced nucleosomal remodeling in the U1 viral promoter region than the treatments with the compounds alone. This more pronounced remodeling correlated with a synergistic reactivation of HIV-1 transcription following the combined treatment prostratin+HDACI, as demonstrated by measuring recruitment of RNA polymerase II to the 5'LTR and both initiated and elongated transcripts. The physiological relevance of the prostratin+HDACI synergism was shown in CD8(+)-depleted peripheral blood mononuclear cells from HAART-treated patients with undetectable viral load. Moreover, this combined treatment reactivated viral replication in resting CD4(+) T cells isolated from similar patients. Our results suggest that combinations of different kinds of proviral activators may have important implications for reducing the size of latent HIV-1 reservoirs in HAART-treated patients. [less ▲]Detailed reference viewed: 55 (6 ULg)
Triom une: la tritherapie du pauvre ?
; ; Vaira, Dolorès et al
in Revue Médicale de Liège (2009), 64(1), 32-6
Despite a relative global stabilization of its incidence, HIV infection remains a major threat for public health, principally in Africa where it concerns more than 22 million people and constitutes the ... [more ▼]
Despite a relative global stabilization of its incidence, HIV infection remains a major threat for public health, principally in Africa where it concerns more than 22 million people and constitutes the first cause of death on the continent. To face the emergency of the HIV/AIDS epidemics on the African continent, the primary goal is to make available to all patients free and efficient antiretroviral medications. Such a goal cannot be dissociated from large scale prevention campaigns. In 2000, Triomune, one of the first fixed dose combinations of three antiretrovirals (stavudine, lamivudine & nevirapine) was launched by the Indian drug company Cipla, specialized in the production of low cost medications. Its convenient pill burden (one pill twice a day) and its very low cost (around 30 US $ per month) make Triomune an appealing solution for the treatment of HIV/AIDS in Africa. Unfortunately, Triomune presents several drawbacks (low genetic barrier, frequent side effects) and one of its constituents is not used in Europe anymore. Other first line treatments are urgently needed. [less ▲]Detailed reference viewed: 36 (6 ULg)
Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: analysis of the HIV-2 Belgium and Luxembourg database.
; ; et al
in BMC Infectious Diseases (2008), 8
BACKGROUND: Guidelines established for the treatment of HIV-1 infection and genotype interpretation do not apply for HIV-2. Data about antiretroviral (ARV) drug efficacy and resistance mutations is scarce ... [more ▼]
BACKGROUND: Guidelines established for the treatment of HIV-1 infection and genotype interpretation do not apply for HIV-2. Data about antiretroviral (ARV) drug efficacy and resistance mutations is scarce. METHODS: Clinical data about HIV-2 infected patients in Belgium and Luxembourg were collected and the effect of ARV therapy on plasma viral load and CD4 counts were analysed. Viral RNA encoding for protease (PR) and reverse transcriptase (RT) from ARV-naive and treated patients were sequenced. RESULTS: Sixty-five HIV-2 infected patients were included in this cohort. Twenty patients were treated with 25 different ARV combinations in a total of 34 regimens and six months after the start of ARV therapy, only one third achieved viral load suppression. All of these successful regimens bar one contained protease inhibitors (PIs). Mean CD4 gains in the group of viral load suppressors and the group of patients treated with PI-containing regimens were respectively significantly higher than in the group of non-suppressors and the group of PI-sparing regimens. The most frequent mutations selected under therapy (compared to HIV-2 ROD) were V71I, L90M and I89V within PR. Within RT, they were M184V, Q151M, V111I and K65R. All of these mutations, except K65R and M184V, were also found in variable proportions in ARV-naive patients. CONCLUSION: Despite a high rate of ARV treatment failure, better virological and immunological results were achieved with PI-containing regimens. The analysis of polymorphic positions and HIV-2 specific mutations selected during therapy showed for the first time that transmission of drug resistant viruses has occurred in Belgium and Luxembourg. The high heterogeneity in ARV combinations reflects a lack of guidelines for the treatment of HIV-2 infection. [less ▲]Detailed reference viewed: 24 (7 ULg)
Prevalence and epidemiology of HIV type 1 drug resistance among newly diagnosed therapy-naive patients in Belgium from 2003 to 2006.
; ; et al
in AIDS Research and Human Retroviruses (2008), 24(3), 355-62
This study is the first prospective study to assess the prevalence, epidemiology, and risk factors of HIV-1 drug resistance in newly diagnosed HIV-infected patients in Belgium. In January 2003 it was ... [more ▼]
This study is the first prospective study to assess the prevalence, epidemiology, and risk factors of HIV-1 drug resistance in newly diagnosed HIV-infected patients in Belgium. In January 2003 it was initiated as part of the pan-European SPREAD program, and continued thereafter for four inclusion rounds until December 2006. Epidemiological, clinical, and behavioral data were collected using a standardized questionnaire and genotypic resistance testing was done on a sample taken within 6 months of diagnosis. Two hundred and eighty-five patients were included. The overall prevalence of transmitted HIV-1 drug resistance in Belgium was 9.5% (27/285, 95% CI: 6.6-13.4). Being infected in Belgium, which largely coincided with harboring a subtype B virus, was found to be significantly associated with transmission of drug resistance. The relatively high rate of baseline resistance might jeopardize the success of first line treatment as more than 1 out of 10 (30/285, 10.5%) viruses did not score as fully susceptible to one of the recommended first-line regimens, i.e., zidovudine, lamivudine, and efavirenz. Our results support the implementation of genotypic resistance testing as a standard of care in all treatment-naive patients in Belgium. [less ▲]Detailed reference viewed: 22 (4 ULg)
Downregulation of CD94/NKG2A inhibitory receptors on CD8+ T cells in HIV infection is more pronounced in subjects with detected viral load than in their aviraemic counterparts.
Zeddou, Mustapha ; Rahmouni, Souad ; Vandamme, Arnaud et al
in Retrovirology (2007), 4
The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small ... [more ▼]
The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated CD8+ T lymphocytes. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In this study, CD94/NKG2A receptor expression on CD8+ T lymphocytes and NK cells was assessed in 46 HIV-1-infected patients (24 viraemic, 22 aviraemic) and 10 healthy volunteers. The percentage of CD8+ T lymphocytes expressing the CD94/NKG2A inhibitory heterodimer was very significantly decreased in HIV-1-infected patients in comparison with non-infected controls. Within the HIV infected patients, the proportion of CD8+ T lymphocytes and NK cells expressing CD94/NKG2A was higher in subjects with undetectable viral loads in comparison with their viraemic counterparts. No significant difference was detected in the proportion of CD8+ T lymphocytes expressing the activatory CD94/NKG2C heterodimer between the HIV-1 infected patients and the healthy donors, nor between the vireamic and avireamic HIV-1 infected patients. In conclusion, chronic stimulation with HIV antigens in viraemic patients leads to a decreased rather than increased CD94/NKG2A expression on CD8+ T lymphocytes and NK cells. [less ▲]Detailed reference viewed: 155 (72 ULg)
Nouvelles approches dans la prise en charge de l'infection a VIH.
; Dellot, Patricia ; Frippiat, Frédéric et al
in Revue Médicale de Liège (2007), 62 Spec No
HIV infection remains a major problem of public health in Belgium as well as globally. The number of new diagnosies of HIV infection in Belgium remains between two and three daily. Given the dramatic ... [more ▼]
HIV infection remains a major problem of public health in Belgium as well as globally. The number of new diagnosies of HIV infection in Belgium remains between two and three daily. Given the dramatic effect of antiretroviral therapy on the mortality due to HIV infection, the number of patients is constantly increasing. The different problems related to HIV care are also changing. Aging of the patients and chronic exposure to antiretroviral medications have induced new complications. We will present in this brief article several new experimental and clinical approaches in which our centre has participated during the last two years. [less ▲]Detailed reference viewed: 41 (10 ULg)
HCV genotype 4 in Belgium: three distinct patterns among patients from European and African origin
Delwaide, Jean ; Reenaers, Catherine ; Gerard, Christiane et al
in European Journal of Gastroenterology & Hepatology (2006), 18(7), 707-712
Background Considered uncommon in western countries some years ago, hepatitis C virus of genotype 4 is now spreading in some areas of Europe. This is assumed to be due to immigration from a region of high ... [more ▼]
Background Considered uncommon in western countries some years ago, hepatitis C virus of genotype 4 is now spreading in some areas of Europe. This is assumed to be due to immigration from a region of high prevalence for this genotype and to propagation among drug users. In the south of Belgium, genotype 4 currently accounts for 10% of hepatitis C virus patients and its prevalence is increasing with time. Objective To better define the genotype 4 carriers' characteristics. Methods In a database comprising 1726 viraemic hepatitis C virus patients, the files of 85 genotype 4 carriers were reviewed. Results Beside the African (58%) and European drug user (15%) subgroups classically described, a third subgroup consisting of European nondrug users (26%) was identified as peculiar: these patients were older, had been mostly contaminated sporadically, presented a great diversity of subtypes, and were mainly of Italian origin. In this subgroup, contamination was supposed to be ancient, having occurred probably in Italy before immigration into Belgium. By contrast, European drug users were infected with only two subtypes (4c/4d and 4), an observation in favour of recent spread. Africans had a great diversity of subtypes, were young, and were mostly contaminated sporadically in their home countries. Despite their epidemiological differences, the clinical management, and in particular the rates of eligibility for treatment, were similar for these three groups. Conclusions Three different patterns of genotype 4 carriers were observed, corresponding to three different spreading profiles. They did not induce, however, different clinical management. [less ▲]Detailed reference viewed: 40 (14 ULg)
Hepatitis C virus genotype 5 in southern Belgium: Epidemiological characteristics and response to therapy
Delwaide, Jean ; Gerard, Christiane ; Reenaers, Catherine et al
in Digestive Diseases & Sciences (2005), 50(12), 2348-2351
Data are scarce on patients infected with hepatitis C virus of genotype 5, due to the low prevalence of this genotype around the world. To better define the characteristics of these patients, we reviewed ... [more ▼]
Data are scarce on patients infected with hepatitis C virus of genotype 5, due to the low prevalence of this genotype around the world. To better define the characteristics of these patients, we reviewed the files of 16 genotype 5 patients. Mean age was 38 +/- 14. All patients were of European origin. Most of them (75%) had been contaminated by transfusion within a short time period (between 1980 and 1991). There were no intravenous drug addicts. Seven patients received treatment. One patient did not respond to interferon (IFN) monotherapy. Of four patients treated with IFN and ribavirin, three became sustained viral responders. Two patients treated with pegylated IFN and ribavirin became sustained viral responders. In our region, genotype 5 patients seem to have been contaminated within a relatively short time period. Treatment with IFN or pegylated IFN and ribavirin gave a high rate (83%) of sustained viral responses. [less ▲]Detailed reference viewed: 38 (8 ULg)
Molecular testing of multiple HIV-1 transmissions in a criminal case
; ; et al
in AIDS (2005), 19(15), 1649-1658
Objective: To test the a priori hypothesis of HIV-1 transmission from one suspect to six recipients in a criminal case. Methods: Partial pol and/or env sequences were obtained for at least two samples of ... [more ▼]
Objective: To test the a priori hypothesis of HIV-1 transmission from one suspect to six recipients in a criminal case. Methods: Partial pol and/or env sequences were obtained for at least two samples of the suspect and the victims. Appropriate local controls were sampled based on epidemiological and subtype criteria. Phylogenetic testing was performed using different reconstruction methods. Results: Phylogenetic analyses consistently inferred a monophyletic cluster for the suspect and victim samples in both genome regions. This was highly supported by parametric and non-parametric bootstrapping techniques. Moreover, the controls most closely related to the suspect-victim cluster had a similar geographical origin to the suspect. Conclusions: Taking into account the limitations on the conclusions that can be drawn from molecular investigations we could infer that our molecular data is consistent with a scenario of multiple HIV transmission between suspect and victims. [less ▲]Detailed reference viewed: 6 (1 ULg)
Alcohol craving and the A1 allele of the D2 dopamine receptor gene
Pinto, Emmanuel ; ; Reggers, Jean et al
in European Psychiatry (2005, March), 20(Suppl. 1), 25Detailed reference viewed: 17 (4 ULg)