Giovanna Melica

Université Paris-Est Créteil Val de Marne - Université Paris 12, Créteil, Île-de-France, France

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Publications (13)47.63 Total impact

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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. · 4.65 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. · 5.34 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. · 5.29 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. · 1.98 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. · 2.37 Impact Factor
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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).
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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. · 11.04 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. · 4.91 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. · 4.76 Impact Factor
  • Revue De Medecine Interne - REV MED INTERNE. 01/2010; 31.
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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 03/2009; 81(4):578-81. · 2.37 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. · 4.91 Impact Factor
  • Medecine Et Maladies Infectieuses - MED MAL INFEC. 01/2008; 38.