Marc Vekemans - Academia.edu (original) (raw)

Papers by Marc Vekemans

Research paper thumbnail of Potential source of human exposure to Mycobacterium bovis in Burkina Faso, in the context of the HIV epidemic

Clinical Microbiology and Infection, 1999

Research paper thumbnail of A 68-year old male presenting with rhabdomyolysis-associated acute kidney injury following concomitant use of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate and pravastatin/fenofibrate: a case report

Journal of Medical Case Reports, 2015

We present what we believe to be the first case in the literature of rhabdomyolysis-induced renal... more We present what we believe to be the first case in the literature of rhabdomyolysis-induced renal failure caused by a probable drug interaction between elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) and pravastatin/fenofibrate. A 68-year old Caucasian man presented with progressive pain in both legs two weeks after commencing treatment with EVG/COBI/FTC/TDF. He was found to have biochemical evidence of rhabdomyolysis and acute renal failure. We emphasize the need for post marketing surveillance of adverse effects of new products. Pharmacokinetic studies are necessary to investigate the levels of pravastatin in patients taking COBI and fenofibrate with and without other comorbidities. Meanwhile, we suggest that creatine kinase levels should be monitored and patients advised to report myalgias when using concomitant EVG/COBI/FTC/TDF and pravastatin/fenofibrate. This case serves as an important reminder to use estimated glomerular filtration rates rather than serum creatinine levels when choosing new medications. If potentially nephrotoxic combinations are started in patients with borderline estimated glomerular filtration rates, it may be prudent to check these filtration rates more frequently than usual. In patients with reduced estimated glomerular filtration rates, potentially nephrotoxic combinations should be avoided wherever possible.

Research paper thumbnail of Zygomycosis in the immunocompromised patient: a case report

Acta bio-medica : Atenei Parmensis, 2006

Zygomycosis is a highly aggressive infection observed in immunocompromised patients, such as thos... more Zygomycosis is a highly aggressive infection observed in immunocompromised patients, such as those with haematological malignancies. The sites most frequently involved are the sinuses and the lungs. New diagnostic tools and new antifungal treatments are essential in order to diagnose early and treat efficiently infections due to moulds. We report a case of sinusitis due to Absidia corymbifera occurring during chemotherapy-induced bone marrow aplasia in a patient with acute leukaemia. The sinusitis was successfully treated with AmBisome, and surgical debridement.

Research paper thumbnail of Toxocariasis Diagnosed in International Travelers at the Institute of Tropical Medicine, Antwerp, Belgium, from 2000 to 2013

PLOS Neglected Tropical Diseases, 2015

Although infection with Toxocara canis or T. catis (commonly referred as toxocariasis) appears to... more Although infection with Toxocara canis or T. catis (commonly referred as toxocariasis) appears to be highly prevalent in (sub)tropical countries, information on its frequency and presentation in returning travelers and migrants is scarce. In this study, we reviewed all cases of asymptomatic and symptomatic toxocariasis diagnosed during post-travel consultations at the reference travel clinic of the Institute of Tropical Medicine, Antwerp, Belgium. Toxocariasis was considered as highly probable if serum Toxocara-antibodies were detected in combination with symptoms of visceral larva migrans if present, elevated eosinophil count in blood or other relevant fluid and reasonable exclusion of alternative diagnosis, or definitive in case of documented seroconversion. From 2000 to 2013, 190 travelers showed Toxocara-antibodies, of a total of 3436 for whom the test was requested (5.5%). Toxocariasis was diagnosed in 28 cases (23 symptomatic and 5 asymptomatic) including 21 highly probable and 7 definitive. All but one patients were adults. Africa and Asia were the place of acquisition for 10 and 9 cases, respectively. Twelve patients (43%) were short-term travelers (< 1 month). Symptoms, when present, developed during travel or within 8 weeks maximum after return, and included abdominal complaints (11/23 symptomatic patients, 48%), respiratory symptoms and skin abnormalities (10 each, 43%) and fever (9, 39%), often in combination. Two patients were diagnosed with transverse myelitis. At presentation, the median blood eosinophil count was 1720/μL [range: 510-14160] in the 21 symptomatic cases without neurological complication and 2080/μL [range: 1100-2970] in the 5 asymptomatic individuals. All patients recovered either spontaneously or with an anti-helminthic treatment (mostly a 5-day course of albendazole), except both neurological cases who kept sequelae despite repeated treatments and prolonged corticotherapy. Toxocariasis has to be considered in travelers returning from a (sub)tropical stay with varying clinical manifestations or PLOS Neglected Tropical Diseases |

Research paper thumbnail of Monocytes contribute to differential immune pressure on R5 versus X4 HIV through the adipocytokine visfatin/NAMPT

PloS one, 2012

The immune system exerts a diversifying selection pressure on HIV through cellular, humoral and i... more The immune system exerts a diversifying selection pressure on HIV through cellular, humoral and innate mechanisms. This pressure drives viral evolution throughout infection. A better understanding of the natural immune pressure on the virus during infection is warranted, given the clinical interest in eliciting and sustaining an immune response to HIV which can help to control the infection. We undertook to evaluate the potential of the novel HIV-induced, monocyte-derived factor visfatin to modulate viral infection, as part of the innate immune pressure on viral populations. We show that visfatin is capable of selectively inhibiting infection by R5 HIV strains in macrophages and resting PBMC in vitro, while at the same time remaining indifferent to or even favouring infection by X4 strains. Furthermore, visfatin exerts a direct effect on the relative fitness of R5 versus X4 infections in a viral competition setup. Direct interaction of visfatin with the CCR5 receptor is proposed as ...

Research paper thumbnail of Stimulation of antiviral cellular immune responses by therapeutic vaccination of HIV-1-infected patients with dendritic cells transfected with gag, tat, rev and nef mRNA

Research paper thumbnail of Do monocytes use the novel adipocytokine Visfatin/NAMPT/PBEF1 to flip the HIV coreceptor switch?

Research paper thumbnail of Lipoplexes carrying mRNA encoding Gag protein modulate dendritic cells to stimulate HIV-specific immune responses

Nanomedicine, 2013

Cationic lipids (Lipofectamine™ [Invitrogen, Merelbeke, Belgium] and 1,2-dioleoyl-3-trimethylammo... more Cationic lipids (Lipofectamine™ [Invitrogen, Merelbeke, Belgium] and 1,2-dioleoyl-3-trimethylammonium-propane/1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and polymers (jetPEI™ and in vivo-jetPEI™ [Polyplus-transfection, Illkirch, France]) were evaluated for their potential to deliver mRNA to monocyte-derived dendritic cells. Lipoplexes and polyplexes, containing mRNA encoding GFP or Gag protein, were incubated with human monocyte-derived dendritic cells and transfection efficiencies were assessed by flow cytometry. Lipofectamine was by far the most efficient in mRNA delivery, therefore it was used in further experiments. Incubation of monocyte-derived dendritic cells isolated from HIV-1-positive donors with mRNA encoding Gag protein complexed to Lipofectamine resulted in 50% transfection. Importantly, coculture of these Gag-transfected dendritic cells with autologous T cells induced an over tenfold expansion of IFN-γ- and IL-2-secreting CD4(+) and CD8(+) T cells. Cationic lipid-mediated mRNA delivery may be a useful tool for therapeutic vaccination against HIV-1. This approach can be applied to develop vaccination strategies for other infectious diseases and cancer.

Research paper thumbnail of Acute hepatitis C infection in a cohort of HIV-infected patients in Belgium

Journal of the International AIDS Society, 2008

Research paper thumbnail of Fever After a Stay in the Tropics: Clinical Spectrum and Outcome in HIV-Infected Travelers and Migrants

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2008

Objective: To investigate the epidemiology and clinical spectrum of fever in HIV-infected returni... more Objective: To investigate the epidemiology and clinical spectrum of fever in HIV-infected returning travelers and migrants.

Research paper thumbnail of B4 Immunotherapy of HIV-1-Infected Patients With Dendritic Cells Transfected With gag and tat-rev-nef mRNA

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2012

ABSTRACT Dendritic cell (DC) immunotherapy was evaluated in 6 adults infected with HIV-1 and stab... more ABSTRACT Dendritic cell (DC) immunotherapy was evaluated in 6 adults infected with HIV-1 and stable under HAART. Autologous monocyte-derived DC electroporated with mRNA encoding HxB2 Gag and Tat-Rev-Nef were administered 4 times at 4 weeks interval, while patients remained on HAART. DC preparation and administration was successful in all patients and only mild adverse events such as skin reactions were seen. There was a significant increase post-DC as compared to pre-DC treatment in magnitude and breadth of HIV-1-specific interferon (IFN)-[gamma] response, in particular to Gag and in T-cell proliferation. Breadth of IFN-[gamma] response and T-cell proliferation were correlated with both CD4 and CD8 polyfunctional T-cell response. Importantly, DC administration induced or increased the capacity of autologous CD8 T-cells to suppress superinfection of CD4 T-cells with the antigen-related IIIB virus and to a lesser extent with other HIV-1 strains. This CD8 T-cell-mediated HIV-1-inhibitory activity was correlated with magnitude and breadth of Gag-specific IFN-[gamma] response. In conclusion, therapeutic immunization of patients stable under HAART with DC expressing HIV-1 antigens is safe and was successful in raising antiviral cellular immune responses which have been related to control of HIV-1 replication, underlining the potential of DC in the treatment of HIV-1.

Research paper thumbnail of Bacteremia due to Stomatococcus mucilaginosus in neutropenic patients in the setting of a cancer institute

Clinical Microbiology and Infection, 2003

This study reviews the clinical manifestations, causes and frequency of Stomatococcus mucilaginos... more This study reviews the clinical manifestations, causes and frequency of Stomatococcus mucilaginosus bacteremia in neutropenic cancer patients. We analyzed retrospectively all clinical and microbiological records of patients with S. mucilaginosus bacteremia. The incidence was compared with that of other pathogens causing bacteremia during neutropenia for the same period. S. mucilaginosus represented 5.9% of bacteremias in our neutropenic patients. Seven patients with hematologic malignancies and one with breast cancer are described. The common clinical presentation was one of sepsis. All patients presented with damaged mucosal barriers as the probable portal of entry, from either stomatitis or enterocolitis. All patients survived.

Research paper thumbnail of Intravesical Instillation of Cidofovir in the Treatment of Hemorrhagic Cystitis Caused by Adenovirus Type 11 in a Bone Marrow Transplant Recipient

Clinical Infectious Diseases, 2005

Hemorrhagic cystitis that occurs late after bone marrow transplantation (BMT) in BMT recipients i... more Hemorrhagic cystitis that occurs late after bone marrow transplantation (BMT) in BMT recipients is often associated with adenovirus or polyomavirus BK infections. Intravesical instillation of cidofovir in a BMT recipient with intractable hemorrhagic cystitis resulted in clinical improvement. Local cidofovir therapy for viral hemorrhagic cystitis could be an alternative to intravenous administration of cidofovir.

Research paper thumbnail of Low Mannose-Binding Lectin Concentration Is Associated with Severe Infection in Patients with Hematological Cancer Who Are Undergoing Chemotherapy

Clinical Infectious Diseases, 2007

Research paper thumbnail of Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulate gag-Specific Immune Responses

Clinical and Developmental Immunology, 2012

A variety of immune-based therapies has been developed in order to boost or induce protective CD8... more A variety of immune-based therapies has been developed in order to boost or induce protective CD8 + T cell responses in order to control HIV replication. Since dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique capability to stimulate naïve T cells into effector T cells, their use for the induction of HIV-specific immune responses has been studied intensively. In the present study we investigated whether modulation of the activation state of DCs electroporated with consensus codon-optimized HxB2 gag mRNA enhances their capacity to induce HIV gag-specific T cell responses. To this end, mature DCs were (i) co-electroporated with mRNA encoding interleukin (IL)-12p70 mRNA, or (ii) activated with a cytokine cocktail consisting of R848 and interferon (IFN)-γ. Our results confirm the ability of HxB2 gag-expressing DCs to expand functional HIV-specific CD8 + T cells. However, although most of the patients had detectable gag-specific CD8 + T cell responses, no significant differences in the level of expansion of functional CD8 + T cells could be demonstrated when comparing conventional or immune-modulated DCs expressing IL-12p70. This result which goes against expectation may lead to a re-evaluation of the need for IL-12 expression by DCs in order to improve T-cell responses in HIV-1-infected individuals.

Research paper thumbnail of High-dose chemotherapy and autologous CD34-positive blood stem cell transplantation for multiple myeloma in an HIV carrier

Bone Marrow Transplantation, 2002

The epidemiology and clinical outcome of multiple myeloma in human immunodeficiency virus (HIV)-p... more The epidemiology and clinical outcome of multiple myeloma in human immunodeficiency virus (HIV)-positive patients is poorly documented. There are uncertainties concerning the optimal management of this rare disorder. We report on the use of myeloablative chemotherapy with autologous stem cell transplantation in an HIV-positive patient with multiple myeloma.

Research paper thumbnail of A general chemotherapy myelotoxicity score to predict febrile neutropenia in hematological malignancies

Annals of Oncology, 2008

Chemotherapy-induced neutropenia is the most common adverse effect of chemotherapy and is often c... more Chemotherapy-induced neutropenia is the most common adverse effect of chemotherapy and is often complicated by febrile neutropenia (FN). The objective of this study is to validate a classification of aggressiveness of a chemotherapy regimen and to evaluate its usefulness in a risk prediction model of FN in patients with hematological cancer at the beginning of a chemotherapy cycle. Two hundred and sixty-six patients were prospectively enrolled and followed during 1053 cycles. Relevant patient informations were collected at the beginning of the first cycle and the number of days of FN were counted in the follow-up [dichotomized (no FN versus &gt;or= 1 day of FN)]. Aggressive chemotherapy regimen is the major predictor of FN [odds ratio 5.2 (3.2-8.4)]. The other independent predictors are the underlying disease, an involvement of bone marrow, body surface &lt;or= 2 m(2), a baseline monocyte count &lt;150/microl and the interaction between the first cycle in the same treatment line and a baseline hemoglobin dosage. A rule of prediction of FN was computed with these characteristics: sensitivity 78.6%, specificity 62.3%, positive predictive value 42.7% and negative predictive value 89.1%. Further studies are needed to validate this score.

Research paper thumbnail of Genotypic Impact of Prolonged Detectable HIV Type 1 RNA Viral Load after HAART Failure in a CRF01_AE-Infected Cohort

AIDS Research and Human Retroviruses, 2011

HIV subtype-specific data on mutation type, rate, and accumulation following HAART treatment fail... more HIV subtype-specific data on mutation type, rate, and accumulation following HAART treatment failure are limited. We studied patterns and accrual of drug resistance mutations in a Cambodian CRF01_AE-infected cohort continuing a virologically failing first-line, nonnucleoside reverse transcriptase inhibitor- (NNRTI-) based, HAART. Between 2005 and 2007, 837 adult HIV-infected patients had regular plasma HIV-1 RNA viral load measurements at Sihanouk Hospital Centre of Hope (SHCH), Cambodia. Drug resistance testing was performed in all patients with HIV-1 RNA &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1000 copies/ml after at least 6 months of HAART. Seventy-one patients with a mean age of 34 years, of whom 68% were male, were retrospectively assessed at virological failure. The median duration of antiretroviral therapy was 12.3 (IQR 7.1-18.23) months, the median CD4 cell count was 173 (IQR 118-256) cells/mm(3), and the mean plasma HIV-1 RNA viral load was 3.9 log (SD 0.72) at failure. NNRTI mutations, M184I/V mutation, thymidine analogue mutations, and K65R were observed in 78.9%, 69%, 20%, and 12.7% of patients, respectively. For 33 patients, genotypic testing was carried out on at least two occasions before the switch to second-line HAART after a median duration of 5.8 (IQR 4.3-6.1) months of virological failure: 54.5% of patients accumulated new mutations with a rate of 1.6 mutations per person-year. Accumulation was seen both for nucleoside and nonnucleoside reverse transcriptase inhibitors, and also in patients with low-level viremia. Subtype-specific data on mutation type, rate, and accumulation after HAART failure are urgently needed to optimize treatment strategies in resource-limited settings.

Research paper thumbnail of Prevalence and Epidemiology of HIV Type 1 Drug Resistance among Newly Diagnosed Therapy-Naive Patients in Belgium from 2003 to 2006

AIDS Research and Human Retroviruses, 2008

This study is the first prospective study to assess the prevalence, epidemiology, and risk factor... 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. 355

Research paper thumbnail of When to switch for antiretroviral treatment failure in resource-limited settings?

Research paper thumbnail of Potential source of human exposure to Mycobacterium bovis in Burkina Faso, in the context of the HIV epidemic

Clinical Microbiology and Infection, 1999

Research paper thumbnail of A 68-year old male presenting with rhabdomyolysis-associated acute kidney injury following concomitant use of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate and pravastatin/fenofibrate: a case report

Journal of Medical Case Reports, 2015

We present what we believe to be the first case in the literature of rhabdomyolysis-induced renal... more We present what we believe to be the first case in the literature of rhabdomyolysis-induced renal failure caused by a probable drug interaction between elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) and pravastatin/fenofibrate. A 68-year old Caucasian man presented with progressive pain in both legs two weeks after commencing treatment with EVG/COBI/FTC/TDF. He was found to have biochemical evidence of rhabdomyolysis and acute renal failure. We emphasize the need for post marketing surveillance of adverse effects of new products. Pharmacokinetic studies are necessary to investigate the levels of pravastatin in patients taking COBI and fenofibrate with and without other comorbidities. Meanwhile, we suggest that creatine kinase levels should be monitored and patients advised to report myalgias when using concomitant EVG/COBI/FTC/TDF and pravastatin/fenofibrate. This case serves as an important reminder to use estimated glomerular filtration rates rather than serum creatinine levels when choosing new medications. If potentially nephrotoxic combinations are started in patients with borderline estimated glomerular filtration rates, it may be prudent to check these filtration rates more frequently than usual. In patients with reduced estimated glomerular filtration rates, potentially nephrotoxic combinations should be avoided wherever possible.

Research paper thumbnail of Zygomycosis in the immunocompromised patient: a case report

Acta bio-medica : Atenei Parmensis, 2006

Zygomycosis is a highly aggressive infection observed in immunocompromised patients, such as thos... more Zygomycosis is a highly aggressive infection observed in immunocompromised patients, such as those with haematological malignancies. The sites most frequently involved are the sinuses and the lungs. New diagnostic tools and new antifungal treatments are essential in order to diagnose early and treat efficiently infections due to moulds. We report a case of sinusitis due to Absidia corymbifera occurring during chemotherapy-induced bone marrow aplasia in a patient with acute leukaemia. The sinusitis was successfully treated with AmBisome, and surgical debridement.

Research paper thumbnail of Toxocariasis Diagnosed in International Travelers at the Institute of Tropical Medicine, Antwerp, Belgium, from 2000 to 2013

PLOS Neglected Tropical Diseases, 2015

Although infection with Toxocara canis or T. catis (commonly referred as toxocariasis) appears to... more Although infection with Toxocara canis or T. catis (commonly referred as toxocariasis) appears to be highly prevalent in (sub)tropical countries, information on its frequency and presentation in returning travelers and migrants is scarce. In this study, we reviewed all cases of asymptomatic and symptomatic toxocariasis diagnosed during post-travel consultations at the reference travel clinic of the Institute of Tropical Medicine, Antwerp, Belgium. Toxocariasis was considered as highly probable if serum Toxocara-antibodies were detected in combination with symptoms of visceral larva migrans if present, elevated eosinophil count in blood or other relevant fluid and reasonable exclusion of alternative diagnosis, or definitive in case of documented seroconversion. From 2000 to 2013, 190 travelers showed Toxocara-antibodies, of a total of 3436 for whom the test was requested (5.5%). Toxocariasis was diagnosed in 28 cases (23 symptomatic and 5 asymptomatic) including 21 highly probable and 7 definitive. All but one patients were adults. Africa and Asia were the place of acquisition for 10 and 9 cases, respectively. Twelve patients (43%) were short-term travelers (< 1 month). Symptoms, when present, developed during travel or within 8 weeks maximum after return, and included abdominal complaints (11/23 symptomatic patients, 48%), respiratory symptoms and skin abnormalities (10 each, 43%) and fever (9, 39%), often in combination. Two patients were diagnosed with transverse myelitis. At presentation, the median blood eosinophil count was 1720/μL [range: 510-14160] in the 21 symptomatic cases without neurological complication and 2080/μL [range: 1100-2970] in the 5 asymptomatic individuals. All patients recovered either spontaneously or with an anti-helminthic treatment (mostly a 5-day course of albendazole), except both neurological cases who kept sequelae despite repeated treatments and prolonged corticotherapy. Toxocariasis has to be considered in travelers returning from a (sub)tropical stay with varying clinical manifestations or PLOS Neglected Tropical Diseases |

Research paper thumbnail of Monocytes contribute to differential immune pressure on R5 versus X4 HIV through the adipocytokine visfatin/NAMPT

PloS one, 2012

The immune system exerts a diversifying selection pressure on HIV through cellular, humoral and i... more The immune system exerts a diversifying selection pressure on HIV through cellular, humoral and innate mechanisms. This pressure drives viral evolution throughout infection. A better understanding of the natural immune pressure on the virus during infection is warranted, given the clinical interest in eliciting and sustaining an immune response to HIV which can help to control the infection. We undertook to evaluate the potential of the novel HIV-induced, monocyte-derived factor visfatin to modulate viral infection, as part of the innate immune pressure on viral populations. We show that visfatin is capable of selectively inhibiting infection by R5 HIV strains in macrophages and resting PBMC in vitro, while at the same time remaining indifferent to or even favouring infection by X4 strains. Furthermore, visfatin exerts a direct effect on the relative fitness of R5 versus X4 infections in a viral competition setup. Direct interaction of visfatin with the CCR5 receptor is proposed as ...

Research paper thumbnail of Stimulation of antiviral cellular immune responses by therapeutic vaccination of HIV-1-infected patients with dendritic cells transfected with gag, tat, rev and nef mRNA

Research paper thumbnail of Do monocytes use the novel adipocytokine Visfatin/NAMPT/PBEF1 to flip the HIV coreceptor switch?

Research paper thumbnail of Lipoplexes carrying mRNA encoding Gag protein modulate dendritic cells to stimulate HIV-specific immune responses

Nanomedicine, 2013

Cationic lipids (Lipofectamine™ [Invitrogen, Merelbeke, Belgium] and 1,2-dioleoyl-3-trimethylammo... more Cationic lipids (Lipofectamine™ [Invitrogen, Merelbeke, Belgium] and 1,2-dioleoyl-3-trimethylammonium-propane/1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and polymers (jetPEI™ and in vivo-jetPEI™ [Polyplus-transfection, Illkirch, France]) were evaluated for their potential to deliver mRNA to monocyte-derived dendritic cells. Lipoplexes and polyplexes, containing mRNA encoding GFP or Gag protein, were incubated with human monocyte-derived dendritic cells and transfection efficiencies were assessed by flow cytometry. Lipofectamine was by far the most efficient in mRNA delivery, therefore it was used in further experiments. Incubation of monocyte-derived dendritic cells isolated from HIV-1-positive donors with mRNA encoding Gag protein complexed to Lipofectamine resulted in 50% transfection. Importantly, coculture of these Gag-transfected dendritic cells with autologous T cells induced an over tenfold expansion of IFN-γ- and IL-2-secreting CD4(+) and CD8(+) T cells. Cationic lipid-mediated mRNA delivery may be a useful tool for therapeutic vaccination against HIV-1. This approach can be applied to develop vaccination strategies for other infectious diseases and cancer.

Research paper thumbnail of Acute hepatitis C infection in a cohort of HIV-infected patients in Belgium

Journal of the International AIDS Society, 2008

Research paper thumbnail of Fever After a Stay in the Tropics: Clinical Spectrum and Outcome in HIV-Infected Travelers and Migrants

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2008

Objective: To investigate the epidemiology and clinical spectrum of fever in HIV-infected returni... more Objective: To investigate the epidemiology and clinical spectrum of fever in HIV-infected returning travelers and migrants.

Research paper thumbnail of B4 Immunotherapy of HIV-1-Infected Patients With Dendritic Cells Transfected With gag and tat-rev-nef mRNA

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2012

ABSTRACT Dendritic cell (DC) immunotherapy was evaluated in 6 adults infected with HIV-1 and stab... more ABSTRACT Dendritic cell (DC) immunotherapy was evaluated in 6 adults infected with HIV-1 and stable under HAART. Autologous monocyte-derived DC electroporated with mRNA encoding HxB2 Gag and Tat-Rev-Nef were administered 4 times at 4 weeks interval, while patients remained on HAART. DC preparation and administration was successful in all patients and only mild adverse events such as skin reactions were seen. There was a significant increase post-DC as compared to pre-DC treatment in magnitude and breadth of HIV-1-specific interferon (IFN)-[gamma] response, in particular to Gag and in T-cell proliferation. Breadth of IFN-[gamma] response and T-cell proliferation were correlated with both CD4 and CD8 polyfunctional T-cell response. Importantly, DC administration induced or increased the capacity of autologous CD8 T-cells to suppress superinfection of CD4 T-cells with the antigen-related IIIB virus and to a lesser extent with other HIV-1 strains. This CD8 T-cell-mediated HIV-1-inhibitory activity was correlated with magnitude and breadth of Gag-specific IFN-[gamma] response. In conclusion, therapeutic immunization of patients stable under HAART with DC expressing HIV-1 antigens is safe and was successful in raising antiviral cellular immune responses which have been related to control of HIV-1 replication, underlining the potential of DC in the treatment of HIV-1.

Research paper thumbnail of Bacteremia due to Stomatococcus mucilaginosus in neutropenic patients in the setting of a cancer institute

Clinical Microbiology and Infection, 2003

This study reviews the clinical manifestations, causes and frequency of Stomatococcus mucilaginos... more This study reviews the clinical manifestations, causes and frequency of Stomatococcus mucilaginosus bacteremia in neutropenic cancer patients. We analyzed retrospectively all clinical and microbiological records of patients with S. mucilaginosus bacteremia. The incidence was compared with that of other pathogens causing bacteremia during neutropenia for the same period. S. mucilaginosus represented 5.9% of bacteremias in our neutropenic patients. Seven patients with hematologic malignancies and one with breast cancer are described. The common clinical presentation was one of sepsis. All patients presented with damaged mucosal barriers as the probable portal of entry, from either stomatitis or enterocolitis. All patients survived.

Research paper thumbnail of Intravesical Instillation of Cidofovir in the Treatment of Hemorrhagic Cystitis Caused by Adenovirus Type 11 in a Bone Marrow Transplant Recipient

Clinical Infectious Diseases, 2005

Hemorrhagic cystitis that occurs late after bone marrow transplantation (BMT) in BMT recipients i... more Hemorrhagic cystitis that occurs late after bone marrow transplantation (BMT) in BMT recipients is often associated with adenovirus or polyomavirus BK infections. Intravesical instillation of cidofovir in a BMT recipient with intractable hemorrhagic cystitis resulted in clinical improvement. Local cidofovir therapy for viral hemorrhagic cystitis could be an alternative to intravenous administration of cidofovir.

Research paper thumbnail of Low Mannose-Binding Lectin Concentration Is Associated with Severe Infection in Patients with Hematological Cancer Who Are Undergoing Chemotherapy

Clinical Infectious Diseases, 2007

Research paper thumbnail of Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulate gag-Specific Immune Responses

Clinical and Developmental Immunology, 2012

A variety of immune-based therapies has been developed in order to boost or induce protective CD8... more A variety of immune-based therapies has been developed in order to boost or induce protective CD8 + T cell responses in order to control HIV replication. Since dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique capability to stimulate naïve T cells into effector T cells, their use for the induction of HIV-specific immune responses has been studied intensively. In the present study we investigated whether modulation of the activation state of DCs electroporated with consensus codon-optimized HxB2 gag mRNA enhances their capacity to induce HIV gag-specific T cell responses. To this end, mature DCs were (i) co-electroporated with mRNA encoding interleukin (IL)-12p70 mRNA, or (ii) activated with a cytokine cocktail consisting of R848 and interferon (IFN)-γ. Our results confirm the ability of HxB2 gag-expressing DCs to expand functional HIV-specific CD8 + T cells. However, although most of the patients had detectable gag-specific CD8 + T cell responses, no significant differences in the level of expansion of functional CD8 + T cells could be demonstrated when comparing conventional or immune-modulated DCs expressing IL-12p70. This result which goes against expectation may lead to a re-evaluation of the need for IL-12 expression by DCs in order to improve T-cell responses in HIV-1-infected individuals.

Research paper thumbnail of High-dose chemotherapy and autologous CD34-positive blood stem cell transplantation for multiple myeloma in an HIV carrier

Bone Marrow Transplantation, 2002

The epidemiology and clinical outcome of multiple myeloma in human immunodeficiency virus (HIV)-p... more The epidemiology and clinical outcome of multiple myeloma in human immunodeficiency virus (HIV)-positive patients is poorly documented. There are uncertainties concerning the optimal management of this rare disorder. We report on the use of myeloablative chemotherapy with autologous stem cell transplantation in an HIV-positive patient with multiple myeloma.

Research paper thumbnail of A general chemotherapy myelotoxicity score to predict febrile neutropenia in hematological malignancies

Annals of Oncology, 2008

Chemotherapy-induced neutropenia is the most common adverse effect of chemotherapy and is often c... more Chemotherapy-induced neutropenia is the most common adverse effect of chemotherapy and is often complicated by febrile neutropenia (FN). The objective of this study is to validate a classification of aggressiveness of a chemotherapy regimen and to evaluate its usefulness in a risk prediction model of FN in patients with hematological cancer at the beginning of a chemotherapy cycle. Two hundred and sixty-six patients were prospectively enrolled and followed during 1053 cycles. Relevant patient informations were collected at the beginning of the first cycle and the number of days of FN were counted in the follow-up [dichotomized (no FN versus &gt;or= 1 day of FN)]. Aggressive chemotherapy regimen is the major predictor of FN [odds ratio 5.2 (3.2-8.4)]. The other independent predictors are the underlying disease, an involvement of bone marrow, body surface &lt;or= 2 m(2), a baseline monocyte count &lt;150/microl and the interaction between the first cycle in the same treatment line and a baseline hemoglobin dosage. A rule of prediction of FN was computed with these characteristics: sensitivity 78.6%, specificity 62.3%, positive predictive value 42.7% and negative predictive value 89.1%. Further studies are needed to validate this score.

Research paper thumbnail of Genotypic Impact of Prolonged Detectable HIV Type 1 RNA Viral Load after HAART Failure in a CRF01_AE-Infected Cohort

AIDS Research and Human Retroviruses, 2011

HIV subtype-specific data on mutation type, rate, and accumulation following HAART treatment fail... more HIV subtype-specific data on mutation type, rate, and accumulation following HAART treatment failure are limited. We studied patterns and accrual of drug resistance mutations in a Cambodian CRF01_AE-infected cohort continuing a virologically failing first-line, nonnucleoside reverse transcriptase inhibitor- (NNRTI-) based, HAART. Between 2005 and 2007, 837 adult HIV-infected patients had regular plasma HIV-1 RNA viral load measurements at Sihanouk Hospital Centre of Hope (SHCH), Cambodia. Drug resistance testing was performed in all patients with HIV-1 RNA &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1000 copies/ml after at least 6 months of HAART. Seventy-one patients with a mean age of 34 years, of whom 68% were male, were retrospectively assessed at virological failure. The median duration of antiretroviral therapy was 12.3 (IQR 7.1-18.23) months, the median CD4 cell count was 173 (IQR 118-256) cells/mm(3), and the mean plasma HIV-1 RNA viral load was 3.9 log (SD 0.72) at failure. NNRTI mutations, M184I/V mutation, thymidine analogue mutations, and K65R were observed in 78.9%, 69%, 20%, and 12.7% of patients, respectively. For 33 patients, genotypic testing was carried out on at least two occasions before the switch to second-line HAART after a median duration of 5.8 (IQR 4.3-6.1) months of virological failure: 54.5% of patients accumulated new mutations with a rate of 1.6 mutations per person-year. Accumulation was seen both for nucleoside and nonnucleoside reverse transcriptase inhibitors, and also in patients with low-level viremia. Subtype-specific data on mutation type, rate, and accumulation after HAART failure are urgently needed to optimize treatment strategies in resource-limited settings.

Research paper thumbnail of Prevalence and Epidemiology of HIV Type 1 Drug Resistance among Newly Diagnosed Therapy-Naive Patients in Belgium from 2003 to 2006

AIDS Research and Human Retroviruses, 2008

This study is the first prospective study to assess the prevalence, epidemiology, and risk factor... 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. 355

Research paper thumbnail of When to switch for antiretroviral treatment failure in resource-limited settings?