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Biomedical subjects

Didier Neau

Publications and source records attributed to Didier Neau.

At least 19 recordsLinked to original sources
PubMed2007

Virological characterization of an infection with a dual-tropic, multidrug-resistant HIV-1 and further evolution on antiretroviral therapy.

We studied a case of recent infection with multidrug-resistant (MDR) HIV-1. Over 16 months off-therapy, the CD4 cell count decreased from 419 to 184 cells/mul. Antiretroviral therapy (ART) then led to an incomplete virological response but to an immunological benefit, concurrently with a shift to CCR5-only tropism and a reduction in replication capacity. ART, even if suboptimal, can be of interest in the case of MDR virus infection.

Adult↗
PubMed2006

Estimation of dynamical model parameters taking into account undetectable marker values.

BACKGROUND: Mathematical models are widely used for studying the dynamic of infectious agents such as hepatitis C virus (HCV). Most often, model parameters are estimated using standard least-square procedures for each individual. Hierarchical models have been proposed in such applications. However, another issue is the left-censoring (undetectable values) of plasma viral load due to the lack of sensitivity of assays used for quantification. A method is proposed to take into account left-censored values for estimating parameters of non linear mixed models and its impact is demonstrated through a simulation study and an actual clinical trial of anti-HCV drugs. METHODS: The method consists in a full likelihood approach distinguishing the contribution of observed and left-censored measurements assuming a lognormal distribution of the outcome. Parameters of analytical solution of system of differential equations taking into account left-censoring are estimated using standard software. RESULTS: A simulation study with only 14% of measurements being left-censored showed that model parameters were largely biased (from -55% to +133% according to the parameter) with the exception of the estimate of initial outcome value when left-censored viral load values are replaced by the value of the threshold. When left-censoring was taken into account, the relative bias on fixed effects was equal or less than 2%. Then, parameters were estimated using the 100 measurements of HCV RNA available (with 12% of left-censored values) during the first 4 weeks following treatment initiation in the 17 patients included in the trial. Differences between estimates according to the method used were clinically significant, particularly on the death rate of infected cells. With the crude approach the estimate was 0.13 day-1 (95% confidence interval [CI]: 0.11; 0.17) compared to 0.19 day-1 (CI: 0.14; 0.26) when taking into account left-censoring. The relative differences between estimates of individual treatment efficacy according to the method used varied from 0.001% to 37%. CONCLUSION: We proposed a method that gives unbiased estimates if the assumed distribution is correct (e.g. lognormal) and that is easy to use with standard software.

AIDS-Related Opportunistic Infections↗
PubMed2006

CD8+HLA-DR+ T lymphocytes are increased in common variable immunodeficiency patients with impaired memory B-cell differentiation.

The recently proposed Piqueras classification of common variable immunodeficiency (CVID) patients is based on flow cytometric quantification of IgD class-switched and CD27 membrane-expressing mature blood B cells. But, many patients also have circulating T cells with immunophenotypic abnormalities, often associated with clinical complications, such as splenomegaly, autoimmune disease, lymphoid proliferation and/or granulomatosis. In 50 unselected CIVD patients, classified according to CD27 and IgD B-cell expression, we analyzed T-lymphocyte subsets according to their expression of HLA-DR and intracellular perforin and/or granzyme B in CD8+ T lymphocytes, CCR7 and CD45RA. CD3+DR+ T-lymphocyte percentages, predominantly CD8+DR+, were significantly higher in patients with clinical complications. MB0 classified patients, characterized by fewer CD27+ B cells, had higher percentages of CD8+DR+ T lymphocytes expressing perforin and/or granzyme with a differentiated effector (CCR7- and CD45RA+) phenotype. In contrast, MB2 patients (with normal CD27+ and IgD- B cells) were free of clinical complications and showed no signs of T-cell activation. MB1 patients (normal CD27+ numbers but fewer IgD- B cells) were either clinically normal or had complications. Combining the set of markers described herein might better define homogeneous groups of patients for etiological studies and clearly segregate patients with clinical complications.

Adolescent↗
PubMed2006

Hepatitis B vaccination in HIV-infected patients: a survey of physicians and patients participating in the Aquitaine cohort.

UNLABELLED: In France, HIV-infected (HIV+) patients are frequently coinfected with hepatitis B virus (HBV) or at risk for this infection. Physicians and their patients should be more committed to HBV prevention than the average population. AIMS: To gain insight into the attitude towards HBV and its vaccination in HIV+ patients from the Aquitaine Cohort and their attending physicians in France. METHODS: A cross-sectional survey based on self-administered questionnaires was performed from November 2002 to June 2003. It targeted 198 physicians from the clinical group on AIDS epidemiology (Groupe d'Epidémiologie Clinique du SIDA en Aquitaine, GECSA) or participating in medical HIV networks in southwestern France; and 512 patients from the cohort. Questions concerned the following items for the physicians: HBV status, prescription of HBV serology and vaccination (frequency, type, schedule), risk factors assessed, reasons for non-vaccination; and for the patients: HBV status, information received, risk factors, attitude towards vaccination. RESULTS: 93% of physicians and 22% of patients stated they were vaccinated against HBV. HBV serological status was reported to be systematically ascertained by 75% of physicians, but post-vaccinal testing was only prescribed by 23% of them. The main reasons for not prescribing more often HBV vaccine were forgetting (79%), difficulty to identify subjects at risk (44%) and being afraid of post-vaccinal complications (32%). Thirty percent of patients reported not to have received any information on HBV vaccination. Overall, 44% considered not to be at risk of infection but 82% of them had been confronted with at least one risk. The main reasons for not having been vaccinated were mostly worry about AIDS (70%), not having been asked by physician (65%) or afraid of complications (58%); nonetheless, 42% of patients were willing to be vaccinated. CONCLUSIONS: Results from this survey underline the need for specific health actions to be undertaken concerning hepatitis B vaccination in HIV+ patients as well as their health care providers.

Adult↗
PubMed2006

Plasma and liver hepatitis C virus variability in patients coinfected with human immunodeficiency virus.

Liver and plasma hepatitis C virus (HCV) variability was compared by E2 cloning and sequencing in three patients coinfected with HCV and human immunodeficiency virus (HIV) before and after interferon treatment and in three patients solely infected with HCV. The plasma and liver samples contained unique sequences. In the patients coinfected with HIV, accumulated random mutations produced mostly nonsynonymous substitutions in contrast to the reduced HCV genetic variability seen after treatment.

Case-Control Studies↗
PubMed2006

Virological responses to atazanavir-ritonavir-based regimens: resistance-substitutions score and pharmacokinetic parameters (Reyaphar study).

OBJECTIVE: To assess the impact of baseline HIV-1 substitutions, individual pharmacokinetic (PK) parameters (Cmin, Cmax, area under the curve [AUC0-->24 h]) and genotype-inhibitory quotient (GIQ) on virological responses (VR) to atazanavir-ritonavir (300 mg/100 mg)-based highly active antiretroviral therapy (HAART) in 71 antiretroviral-experienced, atazanavir-naive patients in virological failure (VF) on HAART. METHODOLOGY: VR was defined as HIV RNA <1.7 log10 copies/ml at week 12 (W12). A clinically relevant genotype-substitutions score for atazanavir-ritonavir was developed and validated (Reyaphar substitutions score). Previously published substitutions scores were also tested. RESULTS: Patients had a median (Q1; O3) of 6 (3; 8) previous treatment lines during 9 (7; 11) years. Baseline (WO) values were as follows: 262 (187; 435) CD4+/microl, 3.9 (2.6; 4.9) log10 HIV-1 RNA copies/ml, 4 (2; 6) protease substitutions and 3 (1; 4) NRTI-related substitutions. Respective steady-state Cmin, Cmax and AUC0-->24 h were 300 (200; 700) ng/ml, 620 (430; 750) ng/ml and 78,000 (61,000; 94,000) ng.h/ml. At W12, 49% of the patients had VR with a median decrease of -1.2 (-0.5; -2.3) log10 HIV-1 RNA copies/ml. The Reyaphar score included 12 baseline protease substitutions from the International AIDS Society USA list that were associated with poorer VR: L10I/F/R/V, K20I/M/R, L241, M461/L, 154L/M/T/V, L63P, A71I/L/V/T, G73A/C/F/T, V771, V82A/F/S/T, 184V, L90M and the polymorphism substitution Q58E. Comparing <5 versus > or =5 Reyaphar substitutions, the W12-W0 HIV-1 RNA decrease was - 1.4 (-0.7; -2.3) versus -0.5 (-1.2; +0.5) log10 copies/ml (P=0.009) with VR in 63% versus 110% (P<10(-4)), respectively. This score predicted VF at W12 with 46% sensitivity, compared to 33% and 28% for the ANRS 2004 and 2005 scores. PK parameters alone were not associated with VR, but GIQ was associated with virological outcome (P=0.04). 150L, known to be correlated with atazanavir-specific resistance, emerged in 2 (8%) of the 24 failing patients with paired genotypes at WO and VF. CONCLUSIONS: These findings highlight the need to cross-validate genotype-based algorithms to interpret substitution impact on virological outcome using different patient databases before their implementation in routine clinical practice.

Adult↗
PubMed2005

Factors associated with the occurrence of AIDS-related non-Hodgkin lymphoma in the era of highly active antiretroviral therapy: Aquitaine Cohort, France.

BACKGROUND: High grade non-Hodgkin lymphoma (NHL) remains the most common Acquired Immune Deficiency Syndrome (AIDS)-associated neoplasia and an important cause of mortality in people living with human immunodeficiency virus (HIV) infection in industrialized countries in the era of highly active antiretroviral therapy (HAART). METHOD: A case-control study was implemented in a large cohort of HIV-infected patients. Case patients had newly diagnosed NHL, and control subjects were matched for CD4(+) cell count, calendar period, sex, and length of follow-up. RESULTS: Variables associated with a decreased risk of NHL were the use of HAART during follow-up for at least 6 months (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.21-0.98), receipt of a diagnosis of AIDS before the censoring date (OR, 0.37; 95% CI, 0.18-0.76), and undetectable level of HIV RNA during follow-up (OR, 0.34; 95% CI, 0.15-0.77). The use of antiherpetic drug for at least 6 months was associated with a nonsignificant decreased risk of NHL (OR, 0.40; 95% CI, 0.11-1.44; P=.16). In multivariate analysis, variables significantly associated with a decreased risk of NHL were the use of HAART for at least 6 months during follow-up (OR, 0.37; 95% CI, 0.16-0.87) and receipt of an AIDS-related diagnosis before the censoring date (OR, 0.44; 95% CI, 0.21-0.93). Age, transmission group, hepatitis B and C coinfections, CD4(+) and CD8(+) cell count nadir, and previous history of herpes virus infection were not associated with an increased risk for NHL. CONCLUSION: The use of HAART for at least 6 months was associated with a decreased risk of NHL, whereas uncontrolled HIV RNA load may be associated with an increased risk. The role of antiherpetic drugs needs further investigation.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Change in atherosclerosis progression in HIV-infected patients: ANRS Aquitaine Cohort, 1999-2004.

This study reported the changes in carotid intima-media thickness (IMT) during a 36-month period in 233 HIV-infected patients. Median IMT increased in the first 12 months and then decreased by month 36. The prevalence of treatment with lipid-lowering agents and protease inhibitor-free highly active antiretroviral therapy regimens increased, whereas smoking prevalence decreased. The progression of atherosclerosis in HIV-infected patients can be controlled. The impact of individual measures to reduce the cardiovascular risk should be evaluated further.

Adult↗
PubMed2005

Occult hepatitis B virus infection in HIV-infected patients with isolated antibodies to hepatitis B core antigen: Aquitaine cohort, 2002-2003.

We prospectively assessed the prevalence of occult hepatitis B virus (HBV) infection by investigating HBV replication in 160 human immunodeficiency virus (HIV)-infected patients with isolated antibodies to hepatitis B core antigen. This prevalence was 0.6% (1 case/160 patients; 95% confidence interval, 0%-3.4%). A second serum sample was collected later from 52 of the patients. HBV DNA was once again undetectable in all patients, except for the sole patient who had previously been found to be HBV DNA positive.

Adult↗
PubMed2005

Clonal analysis of HIV-1 variants in proviral DNA during treatment interruption in patients with multiple therapy failures.

BACKGROUND: Treatment interruption (TI) in antiretroviral-treated patients on virological failure (VF) often results in a shift from resistant to wild-type HIV-1 in plasma. A clonal analysis was set out to determine the importance of archiving of resistant HIV-1 variants during TI and its relationship with the occurrence of a VF after treatment resumption. METHODS: A fragment of the pol gene was cloned and sequenced from peripheral blood mononuclear cells DNA sampled at the end of TI. Clonal sequences were compared to bulk plasma sequences determined before TI, after TI and at VF. RESULTS: Four patients were enrolled; all had a complete reversion to wild-type HIV-1 at the end of TI. In two patients with subsequent VF, archiving of minority resistant variants was detected in proviral DNA. Archived resistant variants were found to be phylogenetically linked to sequences detected before TI and at VF, suggesting the re-expansion of resistant HIV-1 from archived quasi-species. CONCLUSION: In patients having a TI in the context of VF, archiving of resistant HIV-1 variants in proviral DNA can be involved into the mechanisms of further VF after treatment resumption.

Anti-HIV Agents↗
PubMed2005

Risk factors for hyperlactataemia in HIV-infected patients, Aquitaine Cohort, 1999--2003.

The objectives of our study were to describe the characteristics of a subset of patients who had been prescribed serum lactate in clinical practice within a large cohort of HIV-infected patients and to determine the factors associated with hyperlactataemia. Hyperlactataemia (> or =2 mmol/l) was found in 219 [29% (95% confidence interval: 25.3-31.7)] of the 768 HIV-infected participants. In multivariate analysis (logistical regression), an increased risk of hyperlactataemia was associated with increasing age, CD4 count <500/mm3, triglycerides >2.2 mmol/L, lipoatrophy and stavudine use. In a second model coding for the NRTI-based drug combinations, only those including stavudine were associated with an increased risk of hyperlactataemia. In a third model including exposure duration to NRTIs, we estimated a 20% increased risk of hyperlactataemia per year of exposure to didanosine or stavudine. The risk of hyperlactataemia could increase over time in patients treated with these drugs and is also closely associated with increased age, decreased CD4 count, lipodystrophy and increased plasma triglycerides. It could be proposed that patients having one or more of these risk factors undergo regular monitoring of plasma lactate and renal function to prevent lactic acidosis.

Acidosis, Lactic↗
PubMed2004

[The risk of rabies in France and the illegal importation of animals from rabid endemic countries].

INTRODUCTION: Since October 2001, France has the status of a country free from rabies regarding warm-blooded animals. Nevertheless, the risk of rabies is ever present and related to the illegal importation of animals from countries in which rabies is considered to be endemic. OBSERVATION: In 2001, a puppy imported illegally from Morocco died from rabies in Gironde, requiring the prophylactic treatment of 21 persons exposed and the euthanasia of a contact animal, as well as the application of legal measures against the couple at the origin of the importation. CONCLUSION: Illegal importations of animal from areas of rabid enzootics are frequent. It is important to inform all the tourists who visit these countries on the sanitary risks involved, in terms of human and animal health, in bringing such animals back to their own country.

Animals↗
PubMed2004

Fibrosis is worse in HIV-HCV patients with low-level immunodepression referred for HCV treatment than in HCV-matched patients.

Hepatitis C virus (HCV) infection is frequent in human immunodeficiency virus (HIV)-infected patients. It is known to have an aggressive course in significantly immunosuppressed patients, and cirrhosis C has become one of the main causes of mortality in HIV-HCV coinfected patients since the improvement of antiretroviral therapy. The reasons for this severe fibrotic evolution are unclear. This prospective study compared chronic HCV lesions, liver immunocompetent cells, fibrosis and liver HCV loads in 2 cohorts of naive patients referred for HCV treatment: 33 HIV-HCV coinfected patients with CD4 >250/microL and 33 HCV-infected patients matched for the main risk factors of fibrosis. Fibrosis, particularly perisinusoidal fibrosis, was more marked in the coinfected patients. This occurred in the absence of a significant difference in disease activity. The number of CD3+ cells in the liver was higher in the HIV-HCV patients than in the HCV patients. Conversely, the number of liver CD4+ cells was lower in HIV-HCV patients than in HCV patients. The numbers of CD8+ and CD68+ cells were similar in the 2 groups. Finally, liver HCV load, assessed by immunostaining and reverse-transcription polymerase chain reaction, was similar in the 2 groups. We conclude that in the population of HIV-HCV coinfected patients with low-level immunosuppression referred for HCV treatment, fibrosis is worse than in HCV patients and the proportion of CD4+ lymphocytes among CD3+ cells is markedly decreased in the liver, whereas intrahepatic viral load is similar. Our data confirm the need to treat such patients against HCV, and suggest that HIV infection could favor fibrosis via the modulation of the intrahepatic immune response.

Antigens, CD↗
PubMed2003

Time-updated CD4+ T lymphocyte count and HIV RNA as major markers of disease progression in naive HIV-1-infected patients treated with a highly active antiretroviral therapy: the Aquitaine cohort, 1996-2001.

In naive HIV-1 infected patients who start a highly active antiretroviral therapy (HAART), the relationship between time-updated CD4+ cell count, HIV RNA, and clinical progression (new AIDS-defining event or death) is incompletely understood. A 2-step statistical approach was adopted: first, modeling the evolution of the 2 markers taking into account left-censoring of HIV RNA and, second, studying their respective effect on clinical progression. The study sample consisted in 551 previously untreated patients of the Aquitaine Cohort who started their first HAART regimen between 1996 and 2000. During a median follow-up of 33 months, 46 patients experienced a new AIDS-defining diagnosis and 23 died. In multivariate survival analysis, time-updated CD4+ cell count (hazard ratio [HR] = 1.92 for 100 cells/mm3 lower, P < 10(-4) and HIV RNA (HR = 1.30 for 1 log(10) copies/mL higher, P = 0.04) on continuous scale were associated with clinical progression. When analyzing the effect of updated biomarkers using usual thresholds, the association with clinical progression was weaker for CD4+ but still significant (P = 0.007) whereas it remained only significant for updated HIV RNA above 4 log(10) copies/mL (P = 0.01). The prognostic information of updated HIV RNA adjusted on updated CD4+ is significant but depends on how the markers are taken into account. Clinical decisions and interpretation of clinical trial results must weigh the signification of each of these 2 biomarkers.

Adult↗
PubMed2003

Comparison of 2 regimens that include interferon-alpha-2a plus ribavirin for treatment of chronic hepatitis C in human immunodeficiency virus-coinfected patients.

An open-label, randomized trial was conducted to compare the efficacy and safety of 2 regimens of interferon-alpha-2a (IFN-alpha-2a) plus ribavirin for management of chronic hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-coinfected patients. Sixty-eight patients were randomized to receive IFN-alpha-2a at a dosage of either (1) 6 MU given 3 times per week for 24 weeks, followed by 3 MU 3 times per week for an additional 24 weeks (group A; 31 patients); or (2) 9 MU per day for 2 weeks, followed by 3 MU per day for 22 weeks, followed by 3 MU 3 times per week for 24 weeks (group B; 37 patients). Ribavirin was added at week 16 of therapy if HCV RNA remained detectable at week 12. Sustained virological response was achieved in 10 patients (15%; 6 in group A and 4 in group B). HCV genotypes 2 or 3 and a decrease in the HCV load of >or=3 log(10) copies/mL between inclusion and week 4 were associated with virological response. In conclusion, the combination of conventional IFN-alpha-2a and ribavirin has poor virological efficacy in HCV-HIV-coinfected patients.

Adolescent↗
PubMed2003

Hepatitis C virus genetic variability in 52 human immunodeficiency virus-coinfected patients.

The aim of this study was to examine whether hepatitis C virus (HCV) pretreatment quasispecies complexity was linked to virological response or other clinical and biological parameters, in human immunodeficiency virus (HIV)-coinfected patients undergoing anti-HCV treatment. In addition, HCV quasispecies composition is described longitudinally in these patients before, during, and after treatment. The 52 HIV-coinfected patients were included in a randomized therapeutic trial. At inclusion, they had CD4(+) counts of >250/micro l, HIV plasma load of <10,000 copies/ml, and chronic HCV infection with genotype 1 (n = 27), 2 (n = 2) or 3 (n = 23). These values were compared at baseline with 32 HCV-only-infected, interferon-naive patients who were infected with genotype 1, 2, or 3 (n = 16, 1, or 15, respectively). HCV complexity was studied by single-strand conformation polymorphism (SSCP) in E2 hypervariable region 1 (HVR1), and diversity was evaluated at inclusion in 20 coinfected patients by sequencing four major SSCP bands. The baseline number of SSCP bands was identical in HIV-infected and control patients. In HIV-infected patients, HCV complexity was not predictive of sustained virological response to anti-HCV treatment and was unrelated to epidemiological factors, immunological parameters linked to HIV infection (CD4(+) counts, T CD4(+) proliferative responses to HIV-1 p24), protease inhibitor treatment, HCV plasma load, or genotype. HCV diversity was lower in genotype 2- and 3-infected patients. Six months after completion of the anti-HCV treatment, in comparison with baseline, SSCP profiles were modified in 13 of the 21 nonresponding coinfected patients with analyzable samples. In conclusion, in HIV-infected patients, HCV variability had no significant influence on virological response to anti-HCV treatment.

AIDS-Related Opportunistic Infections↗
PubMed2003

Borna disease virus RNA in immunocompromised patients in southwestern France.

Borna disease virus (BDV) is a neurotropic RNA virus with a wide host range. Human infections, although controversial, have been described in Europe, Asia, and the United States. The present study investigated the existence of BDV infections in immunocompromised human beings, namely, 82 human immunodeficiency virus (HIV)-infected and 80 therapeutically immunosuppressed patients. BDV p40 RNAs were detected in peripheral white blood cells with reverse transcription-nested PCR and hybridization in, respectively, 11 (13.41%) and 1 (1.25%) of the two groups of patients. BDV p24 RNAs were identified in only one of those. BDV RNA was detected in the absence of any neuropsychiatrical illness, suggesting that BDV infections may occur in asymptomatic carriers. The severity and particularity of cellular immunosuppression could explain the significantly increased detection of BDV RNA in HIV-infected patients.

Base Sequence↗