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D Neau

Publications and source records attributed to D Neau.

At least 37 records · Page 2Linked to original sources

Prognostic factors of combined viral load and CD4+ cell count responses under triple antiretroviral therapy, Aquitaine cohort, 1996-1998.

OBJECTIVE: To describe the viroimmunologic response and its prognostic factors 6 months after initiating triple antiretroviral therapy in a cohort of HIV-1-infected patients. METHODS: Positive virologic response during follow-up (VL+) was defined as plasma HIV RNA level <500 copies/ml and positive immunologic response (CD4+) as an increase of CD4+ count of at least 50 cells/mm3. Four categories of response were defined: VL+/CD4+; VL+/CD4-; VL-/CD4+ and VL-/CD4-. Prognostic factors were studied through a polytomous logistic regression (VL-/CD4-, as reference). RESULTS: Baseline characteristics of the 478 studied patients were: 22% at AIDS stage, 77% pretreated, median CD4+ cell count 195/mm3 and HIV RNA level 4.42 log. At 6 months 37.5% were VL+/CD4+; 15.7% VL+/CD4-; 23.8% VL-/CD4+ and 23.0% VL-/CD4-. Baseline HIV RNA level was associated to a higher risk of VL-/CD4+ response. More advanced age was associated with a higher risk of isolated immunologic failure (VL+/CD4-), whereas pretreatment and saquinavir therapy were associated with a lower frequency of positive virologic response independently of immunologic response. CONCLUSION: HIV-RNA level, pretreatment, and saquinavir therapy were already known to be linked to therapeutic response. Based on our results, a high baseline HIV-RNA level is associated with isolated immunologic response; moreover, age should be of importance in treatment decision.

Adult↗

Pre- and in-hospital management of community-acquired pneumonia in southern France, 1998-99.

A prospective, hospital-based, multicenter study was undertaken to identify the reasons for hospital admission, to describe antibiotic treatment before and during hospitalization, and to determine the outcome of community-acquired pneumonia (CAP). Data collected included prehospital management of CAP, Pneumonia Outcome Research Team (PORT) classification on admission, in-hospital antibiotic treatment, and predictors of death within 30 days. Among the 215 patients (mean age, 66.7 years; M:F ratio, 1.1) recruited, 24 (11.2%) were living in nursing homes. CAP had been diagnosed prior to admission in 55 (25.6%) patients. At admission, 75 (34.9%) patients had a low risk of death (PORT classification I-II). A pathogen was isolated for 55 (25.6%) patients, primarily Streptococcus pneumoniae (n=18), atypical agents (n=16), influenza virus (n=10), and respiratory syncytial virus (n=4). Amoxicillin (with or without clavulanate), cefotaxime, or ceftriaxone monotherapy was prescribed to 121 (56.3%) patients. Dual combination therapy was prescribed to patients at higher risk of death (PORT classification III-V; OR, 3.09). Mortality was 7%. Logistic-regression analysis identified nursing-home residency (OR, 8.36), serum creatinine > or =88 micromol/l (OR, 7.88), and Pneumonia Outcome Research Team classification (OR, 1.02) as independent predictors of death. CAP remains a serious disease for elderly persons living in nursing homes. This population should benefit from immunization with pneumococcal and influenza vaccines.

Adolescent↗

Trends in causes of death in the Aquitaine cohort of HIV-infected patients, 1995-1997.

OBJECTIVE: To describe trends in the evolution of causes of death in a cohort of HIV-infected patients before and after the introduction of highly active antiretroviral treatment (HAART). METHODS: This descriptive study concerned all the patients of the Aquitaine cohort who died between 1995 and 1997. Causes of deaths were grouped into 13 'deaths due to an AIDS-defining underlying cause', and eight 'non AIDS' categories. Comparisons were performed between two comparable periods of 18 months, January 1995-June 1996 and July 1996-December 1997 to focus on changes introduced by the prescription of HAART in June 1996. RESULTS: Five hundred and thirty-two deaths were notified in 36 months for a total of 3687 patients. The comparison between causes of deaths before and after June 1996 showed a significant difference between the two periods with a decreasing proportion of AIDS causes of death, from 82.7% to 72.2% (p = 0.007). CONCLUSION: HAART treatment has reduced the number and percentage of deaths due to AIDS-related causes among persons who died with HIV infection in South-western France.

Antiretroviral Therapy, Highly Active↗

Incidence and risk factors of severe hypertriglyceridaemia in the era of highly active antiretroviral therapy: the Aquitaine Cohort, France, 1996-99.

OBJECTIVE: To estimate the incidence of serum hypertriglyceridaemia > 6 mm/L (HTG) and identify associated factors in the era of highly active antiretroviral therapy (HAART). METHODS: A prospective cohort, multirisk, both genders, of HIV-infected patients was treated with several patterns of antiretrovirals. Cox's model was used to estimate the effect of explanatory variables documented at the first normal triglyceride measurement (< 2 mm/L) on the subsequent occurrence of HTG. RESULTS: Among 925 patients (27% treated with a protease inhibitor (PI) containing regimen and 48% treated with other HAART combinations) followed 25 months in median with a median triglyceridaemia of 1.1 mm/L at baseline, 70 experienced an HTG, 4.2 cases per 100 person years[95% confidence interval (CI)=2,2,3,3-5]. Univariate analysis retained the following as risk factors of HTG: male gender, homosexual transmission group, greater age, higher body weight, AIDS stage, > or = 2 antiretrovirals including PI, higher triglyceride level and lower CD4+ cell count at baseline. In multivariate analysis, the risk of HTG remained associated with being male homosexual [hazard ratio (HR) = 1.68, P = 0.04], at the AIDS stage (HR = 1.84, P = 0.03), with increased triglyceride level (HR = 2.82 for 1 mm/L higher at baseline, P < 10-3), impaired CD4+ cell count (HR = 1.2 for 100 cells/microL lower, P = 0.02) and increased body weight (HR = 1.3 for 10 kg higher, P = 0.02). CONCLUSIONS: Baseline triglyceride level and being overweight are risk factors of HTG, together with advanced HIV disease, but the contribution of HAART is not demonstrated.

Acquired Immunodeficiency Syndrome↗

Pharmacokinetics and resistance mutations affect virologic response to ritonavir/saquinavir-containing regimens.

The authors assessed the impact of protease and reverse transcription (RT) mutations and individual pharmacokinetic parameters on virologic response to a four-drug regimen including ritonavir/saquinavir. Treatment was given at the start of the study (M0) to 22 HIV-1 protease inhibitor-naive or pretreated patients. Protease and RT genes were sequenced at M0, at the time of virologic failure, or at the end of the follow-up. Plasma ritonavir and saquinavir peak C(max), C(min), and area under the curve (AUC) were determined based on samples taken 0, 1, 2, 3, 4, 6, 8, and 12 hours after administration. HIV-1 RNA decreased to less than 50 copies/mL in 11 patients (group 1). At M0, five of them had no RT mutation and 10 had three or fewer secondary protease mutations with no new mutation during follow-up. Ritonavir and saquinavir pharmacokinetics showed wide interindividual variability. Treatment failed in 11 patients (group 2): 9 had three to eight protease mutations and a mean of 5.8 RT mutations at M0, with emergence of new mutations during follow-up. Pharmacokinetics was similar to those of group 1. The other two patients with virologic failure showed no baseline primary mutation but were the only patients with insufficient saquinavir and ritonavir AUC. The authors showed the complementarity between drug-resistance genotype and individual pharmacokinetics and the potential utility of AUC and Cmax to manage treatment.

CD4 Lymphocyte Count↗

[Anterior uveitis and cidofovir].

PURPOSE: This retrospective study was designed to determine the different parameters involved in the occurrence of uveitis during treatment with codofovir. PATIENTS AND METHODS: This study included 10 patients out of 13 treated with cidofovir for cytomegalovirus (CMV) disease. Ocular examination, CD4+ lymphocyte count, and creatinine clearance were performed for each case of uveitis. RESULTS: During the 17-month study, 20 uveitis cases were analyzed. The first attack occurred after a median interval of 7.6 doses. At the time of ocular inflammation, 65% of the cases had a CD4+ lymphocyte count >=100x10(6)/L, the patients thus had an improved immune function. Half of the patients had a normal creatinine clearance. The patients with a CD4+ lymphocyte count<100x10(6)/L who presented one or more incidents of uveitis had an abnormal clearance, thus probably inducing intraocular storage of the drug. CONCLUSION: The occurrence of anterior uveitis during treatment with cidofovir is induced by the association of several parameters: a previous history of CMV retinitis, improvement of the immune function state, and intraocular storage of the drug.

AIDS-Related Opportunistic Infections↗

Clinical and laboratory findings of cytomegalovirus infection in 115 hospitalized non-immunocompromised adults.

We report a retrospective study of 115 hospitalized non-immunocompromised adults with proved or presumed diagnosis of cytomegalovirus infection. Clinical symptoms were fever (95%), constitutive symptoms (80%), joint and muscle pain (41%), shivering (32%), abdominal pain (26%), non-productive cough (20%), cutaneous eruption (20%), and diarrhea (10%). Examination found hepatomegaly (25%), splenomegaly (23%), cutaneous rash (20%), adenopathy (19%), pharyngitis (9%), jaundice (3%) or signs of meningeal irritation (1%). Seventeen patients had a gastrointestinal form (hepatitis, jaundice, colitis, antral gastritis or cholecystitis), eight had a pattern of hemopathy, two interstitial pneumonitis, two pericarditis, two immune thrombocytopenic purpura, two a polymyalgia rheumatica-like pattern, one thrombotic thrombocytopenic purpura, one cutaneous vasculitis and one meningoencephalitis. Sixty-four percent of the patients had atypical lymphocytosis. Hepatocellular injury occurred in 90% of the patients. Nineteen of the patients had biological immune abnormalities. Cytomegalovirus infection should be mainly suspected in any patient with persistent fever, isolated or associated with signs of poor specificity, or in some patients with visceral manifestations of initially unknown origin.

Adolescent↗

Lipodystrophy, metabolic disorders, and human immunodeficiency virus infection: Aquitaine Cohort, France, 1999. Groupe d'Epidémiologie Clinique du Syndrome d'Immunodéficience Acquise en Aquitaine.

The objective of this study was to estimate the prevalence of and risk factors for clinical lipodystrophy (LD) and metabolic disorders in human immunodeficiency virus (HIV) type 1-infected patients. A cross-sectional survey of the Aquitaine Cohort was performed in January 1999. The clinical diagnosis of LD was categorized as fat wasting (FW), peripheral fat accumulation (FA), and mixed syndromes (MS). Of the 581 patients studied, 61% were treated with protease inhibitors. The overall prevalence of LD was 38% (95% confidence interval [CI], 32-42): prevalence of FW was 16% (95% CI, 13-18); of FA, 12% (95% CI, 10-15); and of MS, 10% (95% CI, 8-13). The prevalences of metabolic abnormalities were 49% (95% CI, 44-53) for lipid disorders and 20% (95% CI, 17-23), for glucose disorders. Factors associated with LD were age (for FW and MS), male sex (for FW), AIDS stage (for MS), body mass index (for FW and FA), waist-to-hip ratio (for FA and MS), and duration of antiretroviral treatment (for FW).

Adult↗

Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Groupe d'Epidémiologie du SIDA en Aquitaine (GECSA).

OBJECTIVE: To compare HIV-disease progression according to changes of plasma HIV RNA observed in the year following initiation of a new antiretroviral treatment. DESIGN: Prospective cohort treated with two nucleoside analogues or a triple combination including a protease inhibitor. METHODS: A Cox model was used to estimate the effect of viral response during the first year after initiation of treatment on the subsequent occurrence of new AIDS-defining events or death. Viral response was fitted either as HIV RNA reduction during the initial 4-12 months of treatment or reduction during the first month. RESULTS: Among 773 patients (47% with triple drug combination) followed for a median period of 27 months, 62 patients experienced a clinical event. Poor viral responders (at least two measurements > 3.7 log10 copies/ml during 4-12 months of treatment) had a higher risk of disease progression than good responders (RNA < 2.7 log10 copies/ml) after adjustment [hazard ratio (HR), 2.24; 95% confidence interval (CI), 1.1 7-4.29]. Intermediate responders (2.7 < or = RNA < or = 3.7 log10 copies/ml) had a risk of progression comparable with that of good responders (HR, 1.43; 95% CI, 0.64-3.22). A large initial viral reduction was also a protective factor for clinical progression (HR, 0.51 for 1 log10 copies/ml increase of the reduction; 95% CI, 0.31-0.85) and was associated with the viral response during the subsequent 4-12 month period. No patient with a reduction < 0.5 log10 copies/ml in the first month was classified as a good responder in the subsequent 4-12 month period (P < 0.01). CONCLUSIONS: A sustained HIV RNA > 3.7 log10 copies/ml should suggest a prompt change of treatment. When the reduction in HIV RNA is < 0.5 log10 after 1 month of treatment, this action should be anticipated. A sustained HIV RNA level between 2.7 and 3.7 log10 copies/ml may permit the deferral of a change of drug regimen according to the patient's history and therapeutic options.

Adult↗

Dual nucleoside regimens in nonadvanced HIV infection: prospective follow-up of 130 patients, Aquitaine Cohort, 1996 to 1998. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine (GECSA).

OBJECTIVE: To describe the response to combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) initiated early in the course of HIV infection under routine circumstances and to research prognostic factors indicating good virologic response. SETTING: Patients of the Aquitaine Cohort, a hospital-based open cohort that had been recruiting since 1987 in five public hospitals of the Aquitaine region in southwestern France. METHODS: Prospective cohort study of antiretroviral-naive patients with CD4+ cell counts >0.350 x 10(9)/L who started dual NRTI therapy between January 1996 and June 1997. Intent-to-treat analysis and multivariate logistic regression were used with data collected up to March 31, 1998. RESULTS: In this study, 130 patients were enrolled with a median follow-up of 14 months. At the time of first prescription, 79% were in U. S. Centers for Disease Control and Prevention (CDC) group A, 16% in group B, and 5% in group C; median CD4+ cell count was 0.466 x 10(9)/L and median HIV RNA level was 4.52 log10 copies/ml. The two main combinations used were zidovudine (AZT) plus zalcitabine (ddC; 38%) and AZT plus didanosine (ddI; 37%). At week 52, median CD4+ and HIV RNA responses were, respectively, +80 cells and -1.6 log; the proportions of patients with HIV RNA level <5000 and <500 copies/ml were 70% and 45%, respectively, and 96% of the patients had a CD4+ cell count >0.350 x 10(9)/L at that time. At their last follow-up, 3 patients had reached been diagnosed with full-blown AIDS and the AIDS-free survival probability at 1 year was 98.2% (95% confidence interval [CI], 93.1-99.6); 1 death had occurred. The only significant variable associated with an undetectable HIV RNA level at 1 year was a lower HIV RNA level at the first prescription of dual therapy. CONCLUSION: Our data indicate that dual nucleoside combinations could be a therapeutic option for patients diagnosed and observed during follow-up in the early course of HIV infection.

AIDS-Related Opportunistic Infections↗

[Hematologic and immunologic manifestations of primary cytomegalovirus infections in non-immunocompromised hospitalized adults].

PURPOSE: Cytomegalovirus (CMV) infection in non-immunocompromised adults can sometimes induce hematological and immunological disorders that may mislead diagnosis. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adolescent↗

Hepatitis B exacerbation with a precore mutant virus following withdrawal of lamivudine in a human immunodeficiency virus-infected patient.

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.

Adult↗

Evaluation of new quantitative assays for diagnosis and monitoring of cytomegalovirus disease in human immunodeficiency virus-positive patients.

Cobas Amplicor CMV Monitor (CMM) and Quantiplex CMV bDNA 2.0 (CMV bDNA 2.0), two new standardized and quantitative assays for the detection of cytomegalovirus (CMV) DNA in plasma and peripheral blood leukocytes (PBLs), respectively, were compared to the CMV viremia assay, pp65 antigenemia assay, and the Amplicor CMV test (P-AMP). The CMV loads were measured in 384 samples from 58 human immunodeficiency virus (HIV) type 1-infected, CMV-seropositive subjects, including 13 with symptomatic CMV disease. The assays were highly concordant (agreement, 0.88 to 0.97) except when the CMV load was low. Quantitative results for plasma and PBLs were significantly correlated (Spearman rho = 0.92). For PBLs, positive results were obtained 125 days before symptomatic CMV disease by CMV bDNA 2.0 and 124 days by pp65 antigenemia assay, whereas they were obtained 46 days before symptomatic CMV disease by CMM and P-AMP. At the time of CMV disease diagnosis, the sensitivity, specificity, and positive and negative predictive values of CMV bDNA 2.0 were 92.3, 97.8, 92.3, and 97.8%, respectively, whereas they were 92.3, 93.3, 80, and 97. 8%, respectively, for the pp65 antigenemia assay; 84.6, 100, 100, and 95.7%, respectively, for CMM; and 76.9, 100, 100, and 93.8%, respectively, for P-AMP. Considering the entire follow-up, the sensitivity, specificity, and positive and negative predictive values of CMV bDNA 2.0 were 92.3, 73.3, 52.1, and 97.1%, respectively, whereas they were 100, 55.5, 39.4, and 100%, respectively, for the pp65 antigenemia assay; 92.3, 86.7, 66.7, and 97.5%, respectively, for CMM; and 84.6, 91.1, 73.3, and 95.3%, respectively, for P-AMP. Detection of CMV in plasma is technically easy and, despite its later positivity (i.e., later than in PBLs), can provide enough information sufficiently early so that HIV-infected patients can be effectively treated. In addition, these standardized quantitative assays accurately monitor the efficacy of anti-CMV treatment.

AIDS-Related Opportunistic Infections↗

Changes in CD4+ cell count and the risk of opportunistic infection or death after highly active antiretroviral treatment. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine.

OBJECTIVE: To study the relationship between the CD4+ cell response after initiation of protease inhibitors and the occurrence of opportunistic infections and survival. DESIGN: Prospective observational cohort study. METHODS: HIV-1-seropositive subjects followed-up in HIV centres of Bordeaux University Hospital, Southwest France who were prescribed at least one available protease inhibitor between January and December 1996 were included in this analysis. A Cox model estimated the independent effect of baseline covariates and CD4+ cell response, considered as a time-dependent covariate, on the occurrence of new AIDS-defining opportunistic infection, new AIDS-defining events, new AIDS-defining opportunistic infection or death. RESULTS: A total of 556 HIV-positive patients were prescribed at least one protease inhibitor: 34% saquinavir, 52% indinavir, and 14% ritonavir. Median CD4+ cell count at baseline was 95 x 10(6)/l and mean plasma HIV RNA was 5.0 log10 copies/ml. After a median follow-up of 230 days, 65 patients experienced a new episode of opportunistic infection, 79 patients experienced at least one AIDS-defining event, and 24 had died. On average, the increase in CD4+ cell count was 42 x 10(6)/l (SD, 74) after a median of 49 days. In the multivariate analysis of opportunistic infection or death, each 50% higher CD4+ cell count at baseline was associated with a 23% reduction [95% confidence interval (CI), 14-30] of risk. Each 50% increase in CD4+ cell count during follow-up was associated with a 9% reduction (95% CI, 2-15) of risk, adjusted for the presence of AIDS prior to protease inhibitor therapy (hazard ratio, 3.76 versus absence of AIDS; P < 0.01) and haemoglobin level (hazard ratio, 0.48 if > 11 g/dl versus <11 g/dl; P < 0.01). CONCLUSION: Our results show, at least indirectly, how protease inhibitors might produce clinical stabilization. This result may be due to improved functionality of CD4+ cells in patients started on protease inhibitors.

AIDS-Related Opportunistic Infections↗