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ABSTRACT: Chronic active hepatitis B exacerbations have been reported following development of resistance to or withdrawal of lamivudine in HIV-infected patients. A 38-year-old woman with HIV and chronic HBV infections was hospitalized because of acute hepatitis. The occurrence of cytolysis with replication of HBV 2 months after withdrawing lamivudine suggests that our patient experienced a severe reactivation of HBV infection due to the modification of her treatment. Sequencing of the HBV precore region showed the strain to be a mutant. We conclude that lamivudine should not be stopped in HIV- and HBV-infected patients, but could be continued at the dose of 100mg/day as used in isolated HBV infection.
Journal of Infection 10/2000; 41(2):192-4. · 4.13 Impact Factor
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F Bonnet,
P Morlat,
D Neau,
J F Viallard, J M Ragnaud,
M Dupon,
P Legendre,
Y Imbert,
F Lifermann,
M Le Bras,
J Beylot,
M Longy-Boursier
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ABSTRACT: Cytomegalovirus (CMV) infection in non-immunocompromised adults can sometimes induce hematological and immunological disorders that may mislead diagnosis.
Case reports of hospitalized non-immunocompromised adults with positive serology for CMV including the presence of immunoglobulin M or seroconversion were assessed in a retrospective study (1981-1998). We focused on clinical and biological abnormalities showing the role of CMV in disruption of functioning of hematological and immunological systems.
Among 115 patients, lymphoma-like syndrome with large adenopathies and/or splenomegaly was diagnosed in eight patients, uncovering underlying CMV infection. Lymphoma was accompanied by hematoma in two patients. Three patients presented leg purpura (with thrombotic thrombocytopenic purpura in one case), one patient had cutaneous vasculitis and on other a Still's disease. Blood abnormalities were mononucleosis (64%), anemia (20%), and thrombopenia (25%) often of peripheral or hemolytic origin or due to hypersplenia. Electrophoresis of serum proteins showed an increase in immune globulins in 56% of the cases and monoclonal abnormality in nine cases. Immunological assessment was conducted in 18 patients. At least one abnormality was depicted in ten patients, consisting of either antinuclear, anti-platelet or anti smooth muscle antibodies, cryoglobulinemia, rheumatoid factor, or reduced complement fixation.
Testing for CMV infection can be of value in case of blood or immunological disorders associated with clinical or biological signs. Although hematological disorders occur early, they are rarely severe. Immunological disorders are rarely symptomatic, but often raise issues regarding the potential genesis of immune diseases in at-risk patients.
La Revue de Médecine Interne 08/2000; 21(7):586-94. · 0.61 Impact Factor
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ABSTRACT: The prognosis for survival of patients infected with the human immunodeficiency virus (HIV) who develop non-Hodgkin lymphoma (NHL) usually is considered to be poor. To the authors' knowledge the impact of highly active antiretroviral therapy, recently introduced in HIV disease case management, has not yet been studied in such circumstances.
All cases of NHL prospectively diagnosed between January 1986 and December 1997 among patients followed in the Aquitaine Cohort were reviewed. The Kaplan-Meier method and the proportional hazards model were used for statistical analysis.
One hundred one NHL diagnoses were validated during the 12-year study period. The median proportional hazards cell count at the time of diagnosis of NHL was 112/mm(3). Histologic findings (Working Formulation classification) were: intermediate grade (N = 23), high grade (N = 61), other (N = 7), and undetermined (N = 10). In 56% of cases, staging classification was Ann Arbor Stage IV. Approximately 73% of patients received a specific NHL chemotherapy. During follow-up, 44% were treated with nucleoside reverse transcriptase inhibitors (NRTIs) alone and 18% with triple therapy including a protease inhibitor (PI). The median survival was 6.0 months. In multivariate analysis, after adjusting for age, year of NHL diagnosis, histologic type, medical center, and transmission category, the following factors recorded at the time of diagnosis of NHL were indicative of an increasing risk of death: CD4+ count </= 50/mm(3) (relative hazard [RH: 2.4, 95% confidence interval [95% CI], 1.2-4.7), hemoglobin </= 10 g/dL (RH: 2.1, 95% CI, 1.1-4.0), and Ann Arbor Stage IV (RH: 2.0, 95% CI, 1.2-3.6). Antiretroviral therapy after the diagnosis of NHL was associated with survival: NRTIs (RH: 0.27, 95% CI, 0.13-0.53) and NRTIs plus PI (RH: 0.08, 95% CI, 0.03-0.21).
Although recently introduced and prescribed, antiretroviral therapy including PIs already has improved the survival of HIV-infected patients with NHL significantly.
Cancer 04/2000; 88(7):1696-702. · 4.77 Impact Factor
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B Hoen,
B Dumon,
M Harzic,
A Venet,
B Dubeaux,
C Lascoux,
Y Bourezane, J M Ragnaud,
A Bicart-See,
F Raffi,
L Beauvais,
H Fleury,
D Séréni
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ABSTRACT: Highly active antiretroviral treatment (HAART) was given early to 64 patients with symptomatic primary human immunodeficiency virus (HIV)-1 infection. At the time of analysis, patients had been followed up for 9-21 months. No patient had died or developed an AIDS-defining event. Survival analysis showed that by month 21 the proportion of patients with plasma HIV-1 RNA <50 copies/mL was 72% (95% confidence interval, 58%-95%) in intention-to-treat analysis. After 18 months of treatment, 50% of the patients with undetectable plasma HIV-1 RNA also had undetectable HIV-1 RNA in peripheral blood mononuclear cells (PBMC). Only 1 of 3 patients had undetectable HIV-1 RNA in lymphoid tissue, while all patients had quantifiable HIV-1 DNA both in PBMC and lymphoid tissue. The median CD4 lymphocyte increase from baseline was 230 cells/microL. These preliminary results support the use of HAART in patients with primary HIV-1 infection.
The Journal of Infectious Diseases 10/1999; 180(4):1342-6. · 6.41 Impact Factor
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F Bonnet,
L Dequae-Merchadou,
J L Taupin,
S Sire,
M Dupon, J M Ragnaud,
D Lacoste,
J Texier-Maugein,
F Romagné,
F Dabis,
J L Pellegrin,
J F Moreau
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ABSTRACT: In a retrospective study, an increase in double-negative (CD3+ CD4- CD8-) (DN) T lymphocytes has been shown to be an independent predictor of disseminated Mycobacterium avium complex (D.MAC) infection in patients with less than 100 CD4+ T cells per mm3. To better characterize this cell expansion, a prospective study was designed. From July 1995 to April 1997, 206 HIV-infected patients with less than 100 CD4+ T cells per mm3 were prospectively followed up and immunophenotyped. The median followup was 1.1 year (+/-0.5 year), and 14 new D.MAC infections were diagnosed among 84 first AIDS-defining events. In univariate and multivariate analyses, D.MAC infections were the only opportunistic infection with a significant increase in DN T-cell percentage (median = 6.6; range = 1.7 to 24.5, P = 0.004) compared with patients without any opportunistic infection. This alteration in T-lymphocyte count could constitute a predictor for D.MAC infection in clinical practice.
Microbes and Infection 09/1999; 1(10):771-6. · 3.10 Impact Factor
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ABSTRACT: The aim of the present study was to better characterize the expansion of double-negative (DN) T cells in vivo in AIDS patients and to ascertain the discrepant response of an immunodepressed immune system towards two distinct mycobacterial infections. In a large cohort of HIV-1 seropositive patients with low CD4(+) T cell counts (<100/mm(3)), we have recently reported on an expansion of DN T cells which was observed only in patients with disseminated Mycobacterium avium infection, toxoplasmosis and Kaposi sarcoma, but not in patients with tuberculosis. The potential differential gammadelta T cells response observed in vivo in AIDS patients with tuberculosis or disseminated M. avium complex infection was investigated by collecting the concomitant or the closest T lymphocyte counts performed within 2 weeks of bacterial diagnosis of 112 disseminated M. avium infection and 41 tuberculosis patients. The DN and gammadelta T cell percentages were different between the two groups (P < 10(-4)) and the expansion of this compartment was found only with disseminated M. avium infections. An analysis of the variable delta2 segment versus pan-delta bearing T cells ratio disclosed a predominance of non-V(delta)2 T cells in these patients whose average values were identical in both groups. It is therefore concluded that the difference seen between these two types of mycobacterial infections concerning the DN T cells only involved the gammadelta T cells although the mechanism of their preferential expansion in disseminated M. avium infections remains a matter of speculation.
International Immunology 09/1999; 11(9):1475-8. · 3.41 Impact Factor
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ABSTRACT: Although T cell clone monospecificity is ensured by several allelic exclusion processes operating at either the genotypic or phenotypic levels, clones expressing two distinct alphabeta or gammadelta TCR have been described in several instances. Thus far, the origin of dual TCR-expressing cells and the homeostatic mechanisms controlling the size of this subset in the periphery remain poorly understood. In the course of a phenotypic analysis of gammadelta T cells in HIV-infected patients, we detected the presence of a T cell subset stained by both Vdelta2- and Vdelta3-specific mAb, which represented a large fraction (up to 16.5%) of gammadelta peripheral blood lymphocytes (PBL) in one HIV patient. The presence of two distinct functional delta chains on these cells was confirmed by phenotypic and molecular analysis of TCR transcripts expressed by Vdelta2+Vdelta3+ T cell clones derived from this patient. For 18 months, the absolute number of these cells varied similarly to the other PBL subsets, before becoming undetectable in blood samples. Moreover, most of these cells expressed CD8 receptors, which are classically found on activated, but not resting, gammadelta T cells. Taken together, these data suggest that dual TCR-expressing T cells are subjected to peripheral expansions and contractions presumably following antigen recognition, which would argue against a systematic counter-selection of these cells during peripheral antigen-driven responses.
International Immunology 05/1999; 11(4):545-52. · 3.41 Impact Factor
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ABSTRACT: To study behavioral risk factors of Kaposi's sarcoma (KS) among HIV infected homosexuals in Bordeaux, southwest France.
A case-control study was performed within the Aquitaine Cohort. Cases of KS surviving in 1995 and homosexuals were systematically enrolled. For each case, two controls were selected among homosexuals surviving in the cohort. Cases and controls were matched on year of diagnosis of HIV infection. Data collection was based on a self administered questionnaire focusing on use of recreational drugs, detailed sexual practices and sexually transmitted diseases in the year preceeding the diagnosis of HIV infection, in the year after the HIV diagnosis and in the year preceeding the diagnosis of KS (or an equivalent period of time for controls).
Twelve cases were matched to 2 controls, 15 cases to one control and 13 cases remained unmatched. Matched analysis identified an association between KS and regular sexual partner (odds ratio = 0.07; 95% confidence interval: 0.01-0.52 and p < 0.001) and active and passive oro-anal intercourse before HIV diagnosis and before KS diagnosis (p = 0.01). In the unmatched analysis including all cases, we found an association between KS and the overall number of sexual partners (p < 0.03) for all periods of interest.
This case-control study identified sexual practices in favor of a sexually transmitted agent of KS.
Revue d Épidémiologie et de Santé Publique 04/1999; 47(2):109-17. · 0.78 Impact Factor
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Clinical Infectious Diseases 02/1999; 28(1):156-7. · 9.15 Impact Factor
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ABSTRACT: We investigated the production of IL-2, IFN-gamma, IL-10 and IL-4 by PBMC from 24 patients with SLE and 10 healthy individuals. Basal and mitogen-stimulated (lipopolysaccharide and phytohaemagglutinin (LPS + PHA)) cytokine production was determined in a whole blood assay (WBA). Supernatants were collected and assayed with specific ELISAs. Although the IL-2 and IFN-gamma contents did not differ significantly between patients and controls under both conditions, statistically significant correlations were found between each cytokine and disease activity (SLAM index) after stimulation (respectively, r = 0.501, P = 0.01 and r = 0.631, P = 0.001). PBMC IL-10 production was significantly higher for patients than controls (P = 0.05), but no correlation between IL-10 levels and the SLAM index was obtained. IL-4 production was not statistically different between SLE patients and controls. For stimulated WBAs, the IL-10/IL-2 and IL-10/IFN-gamma ratios were significantly correlated with disease severity (P = 0.02; P = 0.001, respectively). Overall, our data suggest that SLE is characterized by an elevated production of IL-10, reflecting the basal state of activation of the immune system. During exacerbation of SLE, IL-2 and IFN-gamma are synthesized in larger amounts and may cause the tissue damage observed.
Clinical & Experimental Immunology 02/1999; 115(1):189-95. · 3.36 Impact Factor
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The Journal of Infectious Diseases 12/1998; 178(5):1546-7. · 6.41 Impact Factor
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Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 11/1998; 19(2):198-200.
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ABSTRACT: JC virus (JCV) is thought to reach the central nervous system by a vascular route. To determine whether JCV is conveyed in peripheral blood as latent or reactivated virus, blood leukocytes, plasma, and urine from 50 AIDS patients and plasma and B lymphocytes from 60 AIDS patients were investigated. Peripheral blood from 88 human immunodeficiency virus-negative blood donors was studied. Nested polymerase chain reaction assays allowed the identification of JCV T DNA and VP1 mRNAs. The latter indicate viral replication. Blood harbored JCV DNA in 31.8% of AIDS patients (only 2.3% of blood donors; P > .001) and urine in 56%. VP1 mRNAs were detected in blood of 1 AIDS patient. Notably, 38% of DNA-positive urine samples and 10 cerebrospinal fluid samples (CSF) from AIDS patients with progressive multifocal leukoencephalopathy contained JCV mRNAs. Thus, JCV was significantly more frequent in blood from AIDS patients than from controls, but, in most instances, it was latent, whereas active replication was detected in urine and CSF.
The Journal of Infectious Diseases 07/1998; 177(6):1502-5. · 6.41 Impact Factor
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ABSTRACT: To evaluate the effect of foscarnet on HIV-1 replication in vivo.
Seventeen AIDS patients with cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV) infection, Kaposi's sarcoma (KS), or a combination of these were treated with foscarnet. HIV RNA quantification (bDNA 2.0, Chiron, Emeryville, CA, U.S.A.), CMV pp65 antigenemia (Argene Biosoft, Varilhes, France), and CMV viremia were determined before and during therapy.
Four patients had CMV retinitis (1 with KS), 2 patients had CMV pneumonia (1 with KS), 1 patient had CMV cholecystitis, 2 patients had VZV infection (1 with KS), 1 patient had HSV-2 infection, and 7 patients had KS alone. The decrease in HIV-1 load was -0.73 +/- 0.39 log copies/ml (p = 2.10(-6)) after 3 days of treatment and -1.15 +/- 0.49 log copies/ml (p < 10(-7)) after 10 days of treatment, compared with day 0. Furthermore, reduction of HIV-1 plasma load during foscarnet therapy did not depend on the presence or absence of CMV disease or on a positive pp65 antigenemia at day 0.
We observed decreased HIV-1 plasma load in all patients treated with foscarnet, regardless of presence or absence of clinical or biologic CMV infection. This decrease supports the proposition that foscarnet anti-HIV-1 activity may be of clinical importance.
Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 05/1998; 18(1):46-50.
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International Journal of STD & AIDS 02/1998; 9(2):122-3. · 1.09 Impact Factor
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ABSTRACT: Ticarcillin-clavulanic acid (Claventin) and amikacin were administered in an open study to prevent and treat nosocomial urinary tract infections, to 59 patients after major urological surgery. Postoperative course was event-free in 44 cases. 10 patients presented asymptomatic urinary tract infections due to gram negative bacilli, that did not require any change in antimicrobial therapy. 5 patients experienced symptomatic nosocomial infections, whose one was associated with a methicillin-Resistant Staphylococcus aureus septicemia that was treated by vancomycin. The urinary tract infections were polymicrobial in only 3 cases. The tolerance was quite satisfactory, and the protocol was effective in about 92% of cases. The combination of ticarcillin-clavulanic acid-amikacin is valuable and can be used as first step therapy to preserve the ecology of the patients.
Pathologie Biologie 02/1998; 46(1):73-7. · 1.53 Impact Factor
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ABSTRACT: Recombinant hepatitis B vaccine is usually well tolerated. Clinical and laboratory test manifestations with immunologic mechanisms have nonetheless been described following use of this vaccine. We retrospectively report 7 cases of thrombocytopenia occurring within 3 months (7 weeks on the average) of 1 or following injections of recombinant hepatitis B vaccine. Four boys and 3 girls, average age 12 y, were involved. Three had a history of immune thrombocytopenic purpura. Four had haemorrhagic manifestations. The haemogram showed thrombocytopenia (24 x 10(9)/l on the average) without alterations of the other lines. Infectious and immune aetiologies were excluded in all cases. The course varied after treatment by corticosteroids, high-dose intravenous immunoglobulin, or both. After describing the different manifestations subsequent to recombinant hepatitis B vaccination, we discuss post-vaccinal thrombocytopenias (vaccines in question, mechanisms) and the reality of this entity.
Scandinavian Journal of Infectious Diseases 02/1998; 30(2):115-8. · 1.72 Impact Factor
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ABSTRACT: Relationships were sought between specific anti-HIV cytotoxic T lymphocyte (CTL) responses (against structural and regulatory proteins of the HIV-1 LAI isolate) and plasma and cellular viral loads (VLs) in 17 recently HIV-1-infected patients including 3 displaying asymptomatic primary infection (PI) followed up for 12 months. Plasma VL was correlated directly with CD8 counts and inversely with CD4 counts. Cytotoxic reactions were observed in all patients and directed mainly against structural proteins. The earliest CTL responses were against Gag and Env proteins detected in 87 and 75% of the subjects, respectively, within the first month following PI. Anti-Env and Gag cytotoxic responses were inversely correlated with the plasma VL. Reactions against the pol gene products were thought to be either less involved in or less efficient for the initial decrease of viremia. Responses against regulatory gene products were weak and variable, apart from Nef, which was recognized by half of the subjects. Neutralizing antibodies were not detected before month 3, and were found only in six patients at subsequent times. Two of three patients with asymptomatic PI had a low viral burden and either a delayed response or one limited to a few protein CTL responses, suggesting that the magnitude of the CTL response depends on the initial plasma VL. The third patient displayed viral and CTL parameters identical to those of the patients with symptomatic PI. However, two subjects with symptomatic PI exhibited similarly low plasma VL and moderate CTL responses. Overall, the results suggest that the CTL response may not be the sole factor controlling viremia.
AIDS Research and Human Retroviruses 12/1997; 13(16):1383-94. · 2.25 Impact Factor
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ABSTRACT: We estimated the incidence of the first episodes of cytomegalovirus (CMV) disease in the Aquitaine cohort of HIV-infected subjects, south-western France. Cases were retrospectively investigated using standardized definition criteria. Retinitis was confirmed by an ophthalmologist. Gastro-intestinal lesions were confirmed histologically. Encephalitis was histologically confirmed; it was considered possible if TDM or magnetic resonance imaging (MRI) and symptomatology suggested this diagnosis. Pneumopathy was probable in case of hypoxemia, interstitial X-Ray images and response to CMV treatment; it was confirmed if intranuclear inclusions were identified on biopsy or brushing specimen. In the cohort (n = 3525) followed for an average of 46 months, 158 patients had a first episode of CMV disease. The cumulative incidence was 4.5% and the incidence rate (IR) 1.2 per 100 person-years. The IR was higher for homosexuals (2.0) than for heterosexuals (1.0) and intravenous drug users (0.5). Retinitis was the most frequent site (90 cases), followed by digestive system (40), lung (three confirmed and 17 probable) and central nervous system (eight confirmed and three possible). Sixty-eight percent of the patients were at the AIDS stage when CMV disease was diagnosed, with a mean CD4 count of 42/mm3. The cumulative probability of developing CMV disease 2 years after falling below 200 CD4 lymphocytes/mm3 was 8.0%. Retinitis is by far the most common site for CMV disease. Homosexual transmission of HIV, clinical AIDS and low CD4 count are associated with the occurrence of the first episode of CMV disease.
Journal of Infection 10/1997; 35(2):155-61. · 4.13 Impact Factor
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ABSTRACT: JC virus (JCV) acts as an opportunistic virus in immunocompromised human immunodeficiency virus type 1 (HIV-1)-infected patients. The role of peripheral blood cells in central nervous system invasion, before the onset of progressive multifocal leukoencephalopathy (PML), remains controversial. In order to clarify JCV latency or reactivation status in peripheral blood, 72 HIV-1-infected patients were studied, together with 7 HIV-1-positive PML patients and 50 blood donors. Blood leukocytes, plasma, and B lymphocytes were investigated by two complementary DNA amplification procedures within the early T and late VP1 JCV genes and two reverse transcription techniques for the detection of corresponding early transcripts and mRNAs. JCV DNA was detected in 40.3% of the HIV-1-infected patients but only 8% of the blood donors (P < 0.001). Leukocytes represented 82.7% of the positive samples, but plasma from 12 patients (41.4%) contained JCV DNA. B lymphocytes seemed to be involved in the natural history of JCV but did not represent the unique cell target. JCV DNA was intermittently found in blood, and JCV mRNAs for VP1 capsid protein were detected exclusively in one PML patient. Such observations demonstrate that JCV, when detected in blood, does not undergo active multiplication. They support the JCV hematogenous spread hypothesis, but do not indicate any direct link between peripheral virus and dissemination in the central nervous system at the time of immunodepression.
Journal of Clinical Microbiology 10/1997; 35(9):2288-92. · 4.15 Impact Factor
