Giovanna Melica

University of Paris-Est, La Haye-Descartes, Centre, France

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Publications (20)79.55 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Before the advent of combination antiretroviral therapy (cART), roughly 50% of cases of invasive aspergillosis (IA) associated with human immunodeficiency virus (HIV) infection involved individuals without classical predisposing host factors, and the median survival time was <4 months after diagnosis. We examined if the situation evolved over time using the revised European Organisation for Research and Treatment of Cancer/National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC) definition and analyzed survival trends after diagnosis over 20 years. Methods: A data review committee evaluated 342 medical records that mentioned IA in the French Hospital Database on HIV. Validated cases were classified as fulfilling the EORTC criteria or otherwise as "HIV-related IA." Three periods were analyzed: pre-cART (before 1996), cART era prevoriconazole (1996-2001), and 2002-2011. Results: Among 242 validated cases of IA, 124 (51%) fulfilled the EORTC criteria (EORTC-IA) and 118 (49%) were classified as "HIV-related," with similarly low CD4 cell counts in both groups. The proportion of EORTC-IA cases remained stable across the 3 periods (50%, 48%, and 54%, respectively). The 3-month survival rate improved after the advent of cART (38% vs 69%), with no difference between EORTC-IA and HIV-related IA (hazard ratio [HR], 1.2 95% confidence interval [CI] {0.7-1.8}). Voriconazole exposure decreased mortality in 2002-2011 (HR, 0.1 95% CI [0.01-0.8]). Conclusions: In the cART era, EORTC criteria, developed for use in hematology/oncology, still applied to only half the cases diagnosed among HIV-infected patients. A rapid diagnosis of IA is paramount to improve survival. For patients who do not fulfill the EORTC definition, we suggest that the addition of "HIV infected with a CD4 count <100 cells/µL" to the EORTC host criteria be validated.
    Clinical Infectious Diseases 06/2015; DOI:10.1093/cid/civ492 · 8.89 Impact Factor
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    ABSTRACT: Despite increasing reports of human infection, data about optimal care of Phaeoacremonium infections are missing. We report a case of an infection due to Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides initially localized to skin and soft tissue in a kidney transplanted patient. Despite surgical drainage and excision of the lesion, and combination antifungal therapy with voriconazole and liposomal amphotericin B, a disseminated infection developed, involving the lungs and brain, and leading to death. We have performed a systematic literature review to assess the general features and outcome of human infections due to Phaeoacremonium species. Thirty-six articles were selected and 42 patients, including ours were reviewed. Thirty-one patients (74%) were immunocompromised from organ or bone marrow transplantation (n=17), diabetes or glucose intolerance (n=10), rheumatoid arthritis or Still's disease (n=4), chronic hematological diseases (n=3) and chronic granulomatous disease (n=3). Ten patients (24%) reported initial cutaneous trauma. Skin and soft tissue infections represented 57% of infections (n=24), and disseminated infections, all occurring in immunocompromised patients, 14% of patients (n=6). Main antifungal drugs used were azoles (n=41) and amphotericin B (n=16). Surgical excision or drainage was performed in 64% (n=27). Cure rate was 67 % (n=28). There were 10% cases of treatment failure or partial response (n=4), 19% relapses (n=8) and 7% loss of follow-up (n=3). The death rate was 19% (n=8). Management of Phaeoacremonium infections is complex because of slow laboratory identification and limited clinical data: treatment relies on combination of surgery and systemic antifungal therapy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Journal of clinical microbiology 04/2015; 53(7). DOI:10.1128/JCM.00295-15 · 3.99 Impact Factor
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    ABSTRACT: Diarrhea is a frequent complication after kidney transplantation, with an incidence rate between 22% and 51%. In many cases, the cause remains unknown. We describe here the first case, to our knowledge, of persistent diarrhea associated with Coxsackievirus A19 (CVA19) in a kidney transplant recipient. The patient was a 46-year-old man who received a deceased-donor kidney. He experienced delayed graft function because of donor kidney donation after circulatory determination of death. Maintenance immunosuppression consisted of low-dose cyclosporine, high-dose mycophenolate mofetil (MMF) (3 g/day), and prednisone (10 mg/day). He had severe diarrhea for 2 weeks associated with acute renal failure. No pathogens were found in the stool cultures. Enterovirus detection was positive by real-time polymerase chain reaction, and sequence analysis found CVA19 (from Enterovirus C group). Area under the curve of MMF was 48 mg.h/L. Because of the persistence of diarrhea, MMF was stopped and replaced by azathioprine. The diarrhea disappeared, but serum creatinine did not return to baseline. CVA19 rarely causes gastroenteritis. This case illustrates that MMF is not always the direct cause of diarrhea, and that new clinical infectious diseases will be detected with the expansion of molecular-based DNA diagnostics.
    Transplant Infectious Disease 03/2014; 16(2). DOI:10.1111/tid.12191 · 2.06 Impact Factor
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    ABSTRACT: The role of the thymus in the depletion or restoration of T-cell pool in HIV infection is still debatable. Studies are hampered by the lack of valuable tools to investigate thymic activity. We have evaluated thymic activity using (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography and molecular and phenotypic analyses of thymic precursors. Longitudinal analyses were performed in HIV-infected patients either treatment naive with indication to initiate combination antiretroviral therapy (c-ART) (n = 11) or stable under c-ART (n = 9). Thymic standardized uptake value was significantly lower in c-ART-treated patients as compared with historical age-matched HIV-negative controls. In c-ART-naive patients, baseline thymic standardized uptake value correlated with T-cell repector excision circle levels and naive CD4+ T cells. These patients exhibited a high metabolic lymph node activity positively correlated to the percentage of activated HLA-DR+CD38+ T cells. Basal metabolic thymic activity predicts the gain in CD4+ T cells after c-ART initiation. A decrease of thymic activity, which paralleled circulating plasma IL-7 levels, was noted after c-ART initiation. A metabolic thymic activity is detectable in c-ART naive and correlates with indirect phenotypic and molecular markers of thymic output. This activity may participate to the pool of peripheral naive CD4+ T cells and predicts the magnitude of T-cell reconstitution under treatment.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 06/2012; 61(1):56-63. DOI:10.1097/QAI.0b013e3182615b62 · 4.56 Impact Factor
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    ABSTRACT: To determine the relationship between erythrocyte and plasma ribavirin concentrations in hepatitis C virus (HCV)/HIV-coinfected patients, and to correlate ribavirin exposure with early and sustained virological response (EVR and SVR) and haemoglobin level reductions. Clinical and biological data from 68 HCV/HIV-coinfected patients were recorded at baseline, week 4 (W4), week 12 and at 24 weeks after completion of treatment. Plasma and erythrocyte ribavirin concentrations were determined 12 h after the final ribavirin dose (C(min)). Erythrocyte ribavirin concentrations were 100-fold higher than plasma concentrations, with a significant relationship between them (P < 0.05). In patients with HCV genotype 1 or 4, a plasma ribavirin C(min) threshold of 1.95 mg/L at W4 tended to predict EVR [sensitivity 44%; specificity 87%; AUC 0.67 (95% CI 0.50-0.84)] and was predictive of SVR [sensitivity 58%; specificity 84%; AUC 0.71 (95% CI 0.51-0.90)]. Among patients with these HCV genotypes, an erythrocyte ribavirin C(min) threshold of 146 mg/L at W4 was found to be the best value for discriminating between responders and non-responders for both EVR [sensitivity 67%; specificity 75%; AUC 0.58 (95% CI 0.24-0.93)] and SVR [sensitivity 50%; specificity 80%; AUC 0.70 (95% CI 0.39-1.01)]. We also demonstrated a significant relationship between reduced haemoglobin levels and plasma ribavirin C(min) at W4 (P = 0.05). Therapeutic drug monitoring may be useful for the management of anti-HCV treatment in HCV/HIV-coinfected patients.
    Journal of Antimicrobial Chemotherapy 03/2012; 67(6):1449-52. DOI:10.1093/jac/dks045 · 5.31 Impact Factor
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    ABSTRACT: We describe a new form of acute interstitial nephritis with predominant plasmacytic infiltration in 2 patients with active human immunodeficiency virus 1 (HIV-1) infection. Clinical features included acute kidney injury and proteinuria, but no sicca syndrome. Acute kidney injury was characterized by a high serum creatinine level and nephrotic syndrome with no hematuria or leukocyturia. Kidney biopsy specimens from both patients showed interstitial infiltration by mononuclear cells composed mainly of CD138(+) plasmacytes and diffuse effacement of podocyte foot processes with no deposits. In one patient with Guillain-Barré syndrome, a sural nerve biopsy showed plasmacyte infiltration and immunohistochemistry was strongly positive for HIV-1 p24 protein. In both patients, minor salivary glands and bone marrow were infiltrated by lymphocytes, consistent with B-cell activation induced by HIV-1 infection. Other common causes of acute interstitial nephritis, including B-cell lymphoma and diffuse infiltrative lymphocytosis syndrome, were actively looked for and excluded. Treatment with highly active antiretroviral therapy was effective; symptoms rapidly improved, serum creatinine level decreased, and proteinuria resolved. Exclusion of other common known causes of acute interstitial nephritis and the dramatic response with highly active antiretroviral therapy suggests HIV-1 as a likely cause. The acute interstitial nephritis probably was induced by HIV-1-driven nonspecific B-cell activation. Further investigations are needed to confirm the direct pathogenic role of HIV-1.
    American Journal of Kidney Diseases 02/2012; 59(5):711-4. DOI:10.1053/j.ajkd.2011.12.017 · 5.90 Impact Factor
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    ABSTRACT: Interleukin 7 (IL7) is a critical factor for lymphocyte homeostasis. A dysfunction of the IL7/IL7R pathway has previously been described in HIV-1 infection, and promising results were observed in recent analyses of IL7 for therapeutic use in HIV infected individuals. However, further investigations are still warranted to understand the possible roles of this cytokine. Here, we explored whether the IL7 and IL7RA genetic polymorphisms were associated with the progression of HIV infection. We extensively genotyped the IL7 and IL7RA genes in the GRIV (Genomics of Resistance to Immunodeficiency Virus) cohort, composed of patients with extreme progression profiles - long-term non (LTNP) and rapid (RP) progressors--, and in a healthy control group (CTR). Statistical case-control analyses were performed using the Fisher's exact test, comparing either LTNP vs CTR or RP vs CTR. Three IL7RA SNPs (single nucleotide polymorphisms--rs7701176, rs987106 and rs10491434), but no IL7 SNPs, were significantly associated with rapid disease progression (P < 0.01). In a multi-marker analysis focusing on functional variants, a strong association between an IL7RA haplotype and rapid progression was observed (P = 5.59 x 10(-3)). In summary, our comprehensive genetic study revealed three SNPs and a risk of haplotype associated with rapid progression to AIDS in the IL7RA gene. Interestingly, the haplotype is composed of SNPs previously identified in other inflammatory diseases (e.g., multiple sclerosis) by GWAS and by functional studies. Our results contribute to the growing understanding of the role of IL7/IL7R in HIV disease progression, and more widely, in CD4+ T cell homeostasis.
    Current HIV research 02/2012; 10(2):143-50. DOI:10.2174/157016212799937209 · 1.76 Impact Factor
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    ABSTRACT: Aciclovir (ACV)-resistant Herpes simplex virus type-2 (HSV-2) infections are observed commonly in patients also infected with HIV-1. The use of foscarnet (FOS) in these patients may also lead to resistance. This situation can become a difficult therapeutic challenge. Four cases of patients infected with HIV and with mucocutaneous HSV-2 resistant to ACV and FOS are reported. These patients were treated successfully with topical 5% imiquimod. Imiquimod treatment also appeared to delay the time to recurrence of HSV lesions.
    Journal of Medical Virology 02/2012; 84(2):194-7. DOI:10.1002/jmv.23188 · 2.35 Impact Factor
  • S. Scerra · G. Melica · J.-D. Lelièvre
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    ABSTRACT: Background The recent demonstration of the cure of HIV infection following CCR Δ32/Δ32 stem cell transplantation in a German patient (Berlin patient) paves the way to new therapeutic options. Methods Allogeneic haematopoietic stem cell transplantation (HSCT) have been used since many years during HIV infection and is associated with major toxicity concerns. Several tools have been developed (siRNA, shRNA, Zinc finger proteins) in order to disrupt CCR5 expression in hematopoietic stem cell progenitors. They have been evaluated both in humans and in animal models. Results Results showed that CCR5 knockout strategies do not impair immune reconstitution. They also suggest that the effect of long-term control of HIV in the Berlin patient is related to both CCR5 down regulation and the effects of myeloablative and immunosuppressive therapies used during HSCT. Conclusion In the event of a large use of genetic therapies during HIV infection, beside the context of HSCT, it will be necessary to target several cellular factors in order to obtain a long term control of HIV as observed in the Berlin patient.
    Journal des Anti-Infectieux 09/2011; 13(3). DOI:10.1016/j.antinf.2011.07.003 · 0.08 Impact Factor
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    ABSTRACT: The pathophysiology of acute chest syndrome (ACS) in patients with sickle cell disease is complex, and pulmonary artery thrombosis (PT) may contribute to this complication. To evaluate the prevalence of PT during ACS using multidetector computed tomography (MDCT). We screened 125 consecutive patients during 144 ACS episodes. One hundred twenty-one MDCTs (in 103 consecutive patients) were included in the study. Twenty MDCTs were positive for PT, determining a prevalence of 17% (95% confidence interval, 10-23%). Revised Geneva clinical probability score was similar between patients with PT and those without. D-dimer testing was very often positive (95%) during ACS. A precipitating factor for ACS was less frequently found in patients with PT as compared with those without. Patients with PT exhibited significantly higher platelet counts (517 [273-729] vs. 307 [228-412] 10(9)/L, P < 0.01) and lower bilirubin (28 [19-43] vs. 44 [31-71] μmol/L, P < 0.01) levels at the onset of ACS as compared with others. In addition, patients with PT had a higher platelet count peak (537 [345-785] vs. 417 [330-555] 10(9)/L, P = 0.048) and smaller bilirubin peak (36 [18-51] vs. 46 [32-83] μmol/L, P = 0.048)and lactate dehydrogenase peak (357 [320-704] vs. 604 [442-788] IU/L, P = 0.01) during hospital stay as compared with others. PT is not a rare event in the context of ACS and seems more likely in patients with higher platelet counts and lower hemolytic rate during ACS. Patients with sickle cell disease presenting with respiratory symptoms suggestive of ACS may benefit from evaluation for PT.
    American Journal of Respiratory and Critical Care Medicine 08/2011; 184(9):1022-9. DOI:10.1164/rccm.201105-0783OC · 13.00 Impact Factor
  • AIDS (London, England) 03/2011; 25(6):878-80. DOI:10.1097/QAD.0b013e328344c145 · 5.55 Impact Factor
  • 01/2011; 8(3):1-6. DOI:10.1016/S1166-8598(11)58122-0
  • La Revue de Médecine Interne 12/2010; 31. DOI:10.1016/j.revmed.2010.10.053 · 1.07 Impact Factor
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    ABSTRACT: We report the concentrations of maraviroc in the cerebrospinal fluid (CSF) and plasma of six HIV-1-infected patients with both neurological impairment and detectable HIV-1 replication in CSF. One month after starting maraviroc, the viral load in the CSF decreased significantly (P = 0.005). The median (range) maraviroc concentration in plasma was 347 ng/ml (123-2678). Four patients had CSF concentrations above the protein-adjusted inhibitory concentration (IC90) of 0.57 ng/ml (0.06-10.7) with a median of 102 ng/ml (35-173).
    AIDS (London, England) 08/2010; 24(13):2130-3. DOI:10.1097/QAD.0b013e32833c9353 · 5.55 Impact Factor
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    ABSTRACT: To examine trends in tuberculosis incidence rates in France during the combination antiretroviral therapy (cART) period. From the French Hospital Database on HIV, we selected 72 580 patients (including 14 491 migrants) with no history of tuberculosis, followed between 1 January 1997 and 31 December 2008. We then examined incidence rates of tuberculosis and its risk factors. A total of 2625 patients were diagnosed with tuberculosis either at enrollment (N = 932) or during follow-up (N = 1693). During follow-up, the incidence rate of tuberculosis was 0.40/100 patient-years overall, 0.20 among non-migrants and 1.03 among migrants. Adjusted risk of tuberculosis was 2.01 [95% confidence interval (CI) 1.79-2.26] times higher in migrants than in non-migrants. The adjusted incidence rate of tuberculosis significantly increased in both migrants and non-migrants after 2000-2001, with adjusted risks of 2.50 (95% CI 1.54-4.06) and 1.85 (95% CI 1.27-2.69) in 2008 compared with that in 1997, respectively. Other factors independently associated with a higher incidence of tuberculosis were medical follow-up less than or equal to 6 months, no previous antiretroviral therapy, lower CD4 cell count and higher viral load. Non-migrant patients belonging to HIV-transmission groups other than homosexual men, residing in the Paris area or in French West Indies or with AIDS status were at a supplementary risk. The incidence of tuberculosis is increasing among both migrant and non-migrant HIV-infected patients in France. This is partly because sub-Saharan African migrants represent an increasing fraction of the HIV-infected population in France and also because of late access to care. Co-prescribing tuberculosis preventive therapy with cART might benefit selected patients, such as migrants and patients with late access to care.
    AIDS (London, England) 03/2010; 24(5):763-71. DOI:10.1097/QAD.0b013e3283366747 · 5.55 Impact Factor
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    ABSTRACT: Specific cutaneous lesions of Waldenström macroglobulinemia are rare and include neoplastic cell infiltrates, IgM bullous disease, and so-called IgM-storage papules, which characterize cutaneous macroglobulinosis (CM). We report 2 patients with CM. In patient 1, CM started as small papules, as reported in most of the previously published case studies of CM. In patient 2, lesion evolution was remarkable by its severity, with large ulcerated nodules, and the disease progressed rapidly. As mentioned for half the previously described patients, peripheral neuropathy was suspected in patient 2 and demonstrated in patient 1, with production of antibodies to myelin-associated glycoprotein. To the best of our knowledge, rituximab treatment of Waldenström macroglobulinemia associated with CM has not been described previously. Rituximab caused complete remission of the lesions in patient 1, whereas disease rapidly progressed in patient 2, and the patient died. These observations suggest that evolution of the cutaneous IgM-storage lesions reflects that of the underlying Waldenström macroglobulinemia, and CM is not a prognostic marker.
    Archives of dermatology 02/2010; 146(2):165-9. DOI:10.1001/archdermatol.2009.359 · 4.79 Impact Factor
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    ABSTRACT: Angiitis of the central nervous system (CNS) in patients infected with HIV-1-is often associated with concomitant infection or lymphoproliferative disease of the CNS. Four HAART naïve patients infected with HIV-1 with severe stroke are described. Evidence of vasculitis was found by magnetic resonance angiography. Extensive investigations excluded concomitant opportunistic, lymphoproliferative or autoimmune disorders leading to the diagnosis of primary angiitis of the CNS. Despite initiation of HAART and prolonged suppression of viral replication, these patients remained severely immunosuppressed. The addition of corticosteroids led to a significant improvement of clinical symptoms. Primary angiitis of the CNS should be considered in patients with HIV and stroke. The prognosis of these patients remain poor despite HAART. These observations suggest that the vascular inflammatory process persists despite the control of viral load under HAART in patients with persistent immunosuppression.
    Journal of Medical Virology 04/2009; 81(4):578-81. DOI:10.1002/jmv.21462 · 2.35 Impact Factor
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    ABSTRACT: Expansion of regulatory T (Treg) cells has been described in chronically HIV-infected individuals. We investigated whether HIV-suppressive Treg could be detected during primary HIV infection (PHI). Seventeen patients diagnosed early after PHI (median: 13 days; 1-55) were studied. Median CD4 cell count was 480 cells/microl (33-1306) and plasma HIV RNA levels ranged between 3.3 and 5.7 log10 copies/ml. Suppressive capacity of blood purified CD4CD25 was evaluated in a coculture assay. Fox-p3, IL-2 and IL-10 were quantified by reverse transcriptase (RT)-PCR and intracellular staining of ex vivo and activated CD4+CD25 T cells. The frequency of CD4CD127CD25 T cells among CD4 T cells was lower in patients with PHI compared with chronic patients (n = 19). They exhibited a phenotype of memory T cells and expressed constitutively FoxP3. Similar to chronic patients, Treg from patients with PHI inhibited the proliferation of purified tuberculin (PPD) and HIV p24 activated CD4CD25 T cells. CD4CD25 T cells from patients with PHI responded specifically to p24 stimulation by expressing IL-10. In untreated patients with PHI, the frequency as well as HIV-specific activity of Treg decreased during a 24-month follow-up. A positive correlation between percentages of Treg and both CD4 cell counts and the magnitude of p24-specific suppressive activity at diagnosis of PHI was found. Our data showed that HIV drives Treg, as PHI and these cells persist throughout the course of the infection. A correlation between the frequency of Treg and CD4 T-cell counts suggest that these cells may impact on the immune activation set point at PHI diagnosis.
    AIDS (London, England) 12/2008; 22(18):2451-60. DOI:10.1097/QAD.0b013e328319edc0 · 5.55 Impact Factor
  • Médecine et Maladies Infectieuses 06/2008; 38. DOI:10.1016/S0399-077X(08)73185-8 · 1.24 Impact Factor

Publication Stats

127 Citations
79.55 Total Impact Points


  • 2012
    • University of Paris-Est
      La Haye-Descartes, Centre, France
  • 2008–2012
    • Hôpital Henri Mondor (Hôpitaux Universitaires Henri Mondor)
      Créteil, Île-de-France, France
    • Université Paris-Est Créteil Val de Marne - Université Paris 12
      • Faculty of medicine
      Créteil, Île-de-France, France
  • 2011
    • Hôpital Albert Chenevier – Hôpitaux Universitaires Henri Mondor
      Créteil, Île-de-France, France