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Biomedical subjects

Geneviève Chêne

Publications and source records attributed to Geneviève Chêne.

At least 19 recordsLinked to original sources
PubMed2007

Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis of individual patients' data.

BACKGROUND: Despite three decades of prenatal screening for congenital toxoplasmosis in some European countries, uncertainty remains about the effectiveness of prenatal treatment. METHODS: We did a systematic review of cohort studies based on universal screening for congenital toxoplasmosis. We did a meta-analysis using individual patients' data to assess the effect of timing and type of prenatal treatment on mother-to-child transmission of infection and clinical manifestations before age 1 year. Analyses were adjusted for gestational age at maternal seroconversion and other covariates. FINDINGS: We included 26 cohorts in the review. In 1438 treated mothers identified by prenatal screening, we found weak evidence that treatment started within 3 weeks of seroconversion reduced mother-to-child transmission compared with treatment started after 8 or more weeks (adjusted odds ratio [OR] 0.48, 95% CI 0.28-0.80; p=0.05). In 550 infected liveborn infants identified by prenatal or neonatal screening, we found no evidence that prenatal treatment significantly reduced the risk of clinical manifestations (adjusted OR for treated vs not treated 1.11, 95% CI 0.61-2.02). Increasing gestational age at seroconversion was strongly associated with increased risk of mother-to-child transmission (OR 1.15, 95% CI 1.12-1.17) and decreased risk of intracranial lesions (0.91, 0.87-0.95), but not with eye lesions (0.97, 0.93-1.00). INTERPRETATION: We found weak evidence for an association between early treatment and reduced risk of congenital toxoplasmosis. Further evidence from observational studies is unlikely to change these results and would not distinguish whether the association is due to treatment or to biases caused by confounding. Only a large randomised controlled clinical trial would provide clinicians and patients with valid evidence of the potential benefit of prenatal treatment.

Coccidiostats↗
PubMed2007

Salvage therapy with amprenavir, lopinavir and ritonavir is durably potent in HIV-infected patients in virological failure: 1-year results.

We report the results of the extended follow-up at one year of a randomized trial evaluating the virological efficacy of a salvage therapy combining lopinavir and amprenavir with either 200 or 400 mg/day ritonavir, along with optimized nucleoside reverse transcriptase inhibitors, in patients carrying multidrug-resistant isolates. The combination of amprenavir, lopinavir and ritonavir (400 mg/day) is durably potent, yielding a sustained virological response (HIV RNA < 50 copies) in 39% of cases.

Anti-HIV Agents↗
PubMed2006

Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy.

BACKGROUND: Immune restoration following combination antiretroviral therapy (cART) questions the maintenance of prophylaxis among HIV-infected patients with cryptococcosis. OBJECTIVE: To describe the long-term outcome after the diagnosis of cryptococcosis at the cART era. DESIGN: Multicentre cohort of patients with a diagnosis of cryptococcosis between 1996 and 2000, follow-up until December 2002. Comparison with a historical cohort (1990-1994) for survival. SETTING: Eighty-four French AIDS clinical centres. PATIENTS: Two-hundred and forty HIV-infected adult patients at the cART era and 149 at the pre-cART era experiencing a first episode of culture-confirmed cryptococcosis. RESULTS: In the cART era, 82/189 patients surviving more than 3 months after initiation of antifungal therapy had their maintenance therapy interrupted with a subsequent median follow-up of 19 months. Their relapse rate per 100 person-years was 0.9 [95% confidence interval (CI),0.0-2.0]. When considering the whole cART cohort, probability of reaching negative serum cryptococcal antigen was 71% after 48 months of follow-up. A CD4 cell count < 100/microl [relative risk (RR), 5.5; 95% CI, 1.3-22.2], antifungal therapy < 3 months over the past 6 months [RR, 5.0; 95% CI, 1.1-22.3] and serum cryptococcal antigen titre > or = 1/512 [RR, 3.5; 95% CI, 1.1-10.8] were associated with a higher rate of cryptococcosis relapse. The mortality rate per 100 person-years was 15.3 [95% CI,12.2-18.4] in the cART era versus 63.8 [95% CI,53.0-74.9] in the pre-cART era although early mortality did not differ between the two periods. CONCLUSION: Overall survival after cryptococcosis has dramatically improved at the cART era. Immune restoration and low serum cryptococcal antigen titres are associated with lower cryptococcosis relapse rates.

AIDS-Related Opportunistic Infections↗
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

No association between GB virus C infection and disease progression in HIV-2-infected patients from the French ANRS HIV-2 cohort.

Out of 183 HIV-2-infected patients tested in the ANRS CO8 HIV-2 cohort, 69 were exposed to GB virus C (GBV-C), yielding a prevalence of 38% (95% CI 30.7, 45.2). There was no significant difference between the CD4 cell count and HIV-2-RNA plasma viral load in patients exposed and not exposed to GBV-C. After adjusting for age and CD4 cell count, co-infection with GBV-C was not associated with clinical progression (hazard ratio 0.78; 95% CI 0.24-2.56, 16 clinical events).

Adult↗
PubMed2006

An additive/subtractive genotypic score as a determinant of the virological response to didanosine in HIV-1 infected patients.

OBJECTIVE: To assess the genotypic determinants of the virological response (VR) to didanosine (ddI) in nucleoside reverse transcriptase inhibitors (NRTI)-experienced patients. METHODS: Human immunodeficiency virus type 1 (HIV-1) genotype was determined at baseline in 74 ddI-naive-patients with baseline viral load >500 copies/ml and receiving ddI as part of a new regimen. VR was defined as a plasma HIV-1 RNA <50 copies/ml after three months on ddI. NRTI resistance mutations associated with higher or lower frequencies of VR with a p-value<0.25 were retained in different sets of mutations, where the mutations associated with a worse VR were added, whereas the mutations associated with a better VR were subtracted. The most significant mutation scores were then studied in a multivariate analysis. RESULTS: Changes at three codons (M41L, L210W, T215Y/F/D/C/E) were associated with a worse VR and three mutations (K70R, M184V, K219Q) with a better VR. The strongest association with the VR was obtained with the score M41L+L210W+T215Y/F/D/C/E-K70R-K219Q. The score was independently associated with the VR in the multivariate analysis. CONCLUSION: Taking into account the mutations associated with a better VR may improve genotypic resistance algorithms. Our results are of interest for the management of antiretroviral therapy in NRTI-experienced patients.

Algorithms↗
PubMed2006

Low genetic barrier to large increases in HIV-1 cross-resistance to protease inhibitors during salvage therapy.

HIV-1 resistance to protease inhibitors (PIs) is characterized by extensive cross-resistance within this drug class. Some PIs, however, appear less affected by cross-resistance and are often prescribed in salvage therapy regimens for patients who have failed previous PI treatment. To examine the capacity of HIV-1 to adapt to these treatment changes, we have followed the evolution of HIV-1 protease genotypes and phenotypes in 21 protease-inhibitor-experienced patients in whom 26 weeks of an aggressive salvage regimen associating lopinavir, amprenavir and ritonavir failed to suppress viral replication. Baseline genotypes exhibited a median of seven resistance mutations in the protease. After 26 weeks of treatment, changes in protease genotypes were seen in 13/21 patients. The evolution of these protease genotypes was rapid, with more than one-third of the changes occurring during the first 6 weeks. Although the mean number of additional mutations was small (2.15 new mutations at week 26) these mutations were sufficient to promote remarkable changes in resistance phenotype. In several patients, some of the new mutations were found to exist before salvage treatment as part of minority quasi-species. Thus, in the face of the strong pharmacological pressure exerted by combinations of PIs to which it has never been exposed, and in spite of limited cross-resistance to these drugs before salvage therapy, HIV-1 can rapidly adapt its resistance genotype and phenotype at a minimal evolutionary cost.

Drug Administration Schedule↗
PubMed2005

Biases in observational studies of the effect of prenatal treatment for congenital toxoplasmosis.

The paper reviews methodological difficulties that arise when using observational studies to evaluate the effect of prenatal screening and treatment. The principle of each difficulty is described and then illustrated by a clinical example of toxoplasmosis in pregnancy and its consequences. Methods to deal with these difficulties are described. Given the limitations of existing observational studies and lack of randomised controlled trials, a systematic review of cohort studies offers the best approach for exploring potential biases.

Adult↗
PubMed2005

Use of a Bayesian approach to decide when to stop a therapeutic trial: the case of a chemoprophylaxis trial in human immunodeficiency virus infection.

From 1996 to 1998, a phase III, placebo-controlled, therapeutic trial was conducted in Abidjan, Ivory Coast, to assess the efficacy of cotrimoxazole prophylaxis in reducing severe morbidity in adults at early stages of human immunodeficiency virus infection. The authors used the real data from this trial to simulate three Bayesian interim analyses. Three prior distributions were considered: a noninformative one, a skeptical one, and one based on external information. The posterior distribution was calculated by using directed acyclic graphs and Gibbs sampling. This Bayesian approach showed different results according to the prior distribution chosen. Although use of the noninformative prior would have led to stopping the trial at the same time that the frequentist approach would have, the skeptical prior would have led to continuing it, and the prior based on external data would have led to stopping it 1 year earlier.

Anti-Infective Agents↗
PubMed2005

Immunological markers after long-term treatment interruption in chronically HIV-1 infected patients with CD4 cell count above 400 x 10(6) cells/l.

OBJECTIVE: To analyse immunological markers associated with CD4+ lymphocyte T-cell count (CD4+) evolution during 12-month follow-up after treatment discontinuation. METHOD: Prospective observational study of chronically HIV-1 infected patients with CD4+ above 400 x 10(6) cells/l. RESULTS: CD4+ changes took place in two phases: an initial rapid decrease in the first month (-142 x 10(6) cells/l on average), followed by a slow decline (-17 x 10(6) cells/l on average) The second slope of CD4+ decline was not correlated with the first and only baseline plasma HIV RNA was associated with it. The decline in CD4+ during the first month was steeper in patients with higher CD4+ and weaker plasma HIV RNA baseline levels. Moreover, the decline was less pronounced (P < 10(-4)) in patients with CD4+ nadir above 350 x 10(6) cells/l (-65 x 10(6) cells/l per month) in comparison with those below 350 x 10(6) cells/l (-200 x 10(6) cells/l per month). A high number of dendritic cells (DCs) whatever the type was associated with high CD4+ at the time of treatment interruption and its steeper decline over the first month. Moreover, the myeloid DC level was stable whereas the lymphoid DC count, which tended to decrease in association with decrease in CD4+, was negatively correlated with the HIV RNA load slope. CONCLUSIONS: The results support the use of the CD4+ nadir to predict the CD4+ dynamic after treatment interruption and consideration of the CD4+ count after 1-month of interruption merely reflects the 12-month level of CD4+. Although DCs seem to be associated with the CD4+ dynamic, the benefit of monitoring them has still to be defined.

Adult↗
PubMed2005

Can highly active antiretroviral therapy be interrupted in patients with sustained moderate HIV RNA and > 400 CD4+ cells/microl? Impact on immunovirological parameters.

Because the effects of treatment interruption on patients with >400 CD4(+) cells/microl and prolonged moderate HIV loads is unknown, their HIV1 RNA and DNA loads, plasma, and PBMC resistance mutations and CD4+ kinetics were studied during 12 months of treatment interruption. Fifty-seven patients were included: 28 with undetectable (median 40 months) and 29 with moderate (>1 year) HIV1 RNA levels (3.3 log10 copies/ml) at the baseline M0. HIV1 RNA and CD4+ counts were determined monthly. PBMC HIV1 DNA was quantified (real-time PCR) and its reverse transcriptase (RT) and protease (PR) genotypes analyzed (M0, M6, M12). Regardless of HIV1 RNA detectability at the baseline M0, all patients had comparable HIV1 RNA (median 4.6), DNA (median 2.9), CD4+ (median 455) at month 12 (M12). The decisive moment was month 1 (M1), when the HIV1 RNA increase and CD4 decline stabilized, rendering M0 differences non-significant and predicting outcome. The lower the CD4+ nadir was before HAART, the steeper the CD4+ decline at M1. HIV1 DNA shifted to wild-type genotype in 47% (M6) and 79% (M12) of RT; 64% of PR major resistance mutations disappeared (M12). Treatment interruption is possible, regardless of the baseline M0 HIV RNA status, but it must take into consideration the CD4+ nadir, an outcome predictor, to initiate HAART before too severe depletion to preserve the possibility of treatment interruption. HIV1 DNA genotyping helps monitor patients with undetectable HIV RNA at M0.

Anti-HIV Agents↗
PubMed2005

Intermittent viremia during first-line, protease inhibitors-containing therapy: significance and relationship with drug resistance.

BACKGROUND: In HIV-infected patients on first-line antiretroviral therapy, the significance of intermittent viremia and their relationship with drug resistance remain unclear. OBJECTIVE: To study the virological characteristics of intermittent viremia (IV) and the association between IV and later virological failure (VF) in patients on a first-line, PI-containing therapy. STUDY DESIGN: Antiretroviral-naive patients were enrolled in the APROVIR substudy of the prospective, multicenter APROCO cohort at the time they initiated a PI-containing therapy and were followed-up at month 1 and every 2 months. IV was defined as plasma HIV-1 RNA > 500 copies/ml on a single specimen. VF were defined as: (1) viral rebound on two consecutive plasma specimens with HIV-1 RNA > 500 copies/ml after an initial response below 500 copies/ml, or (2) persistence of plasma HIV-1 RNA> or =500 copies/ml during the first year of follow-up. Genotypic resistance analysis was performed at baseline and at the time of IV. PI plasma concentrations were determined at the time of IV. RESULTS: IV was found in 20/219 patients in a 2 years follow-up. The occurrence of IV in the first year of therapy was associated with a higher risk of virological failure during the second year (p = 0.03). Genotypic resistance at the time of IV was found in only 4/16 patients and was not predictive of a subsequent virological failure. PI plasma levels suggested lack of adherence in 50% of patients with IV. CONCLUSION: The occurrence of IV > 500 copies/ml among patients on first-line, PI-containing ART is suggestive of a lack of adherence rather than the selection of resistant variants and should lead to an intensification of adherence monitoring in order to reduce the risk of subsequent VF.

Anti-HIV Agents↗
PubMed2005

Liver disease as a major cause of death among HIV infected patients: role of hepatitis C and B viruses and alcohol.

BACKGROUND/AIMS: We analyzed the characteristics of HIV infected patients who died from liver disease, focusing on hepatitis virus co-infection. METHODS: One-hundred and eighty-five French hospital departments involved in HIV/AIDS management prospectively notified all deaths occurring in 2000. Patients whose hepatitis C (HCV) and hepatitis B (HBV) serostatus was known were classified as being infected by HCV alone, HBV alone (HBsAg positive), both HCV and HBV, or neither HCB nor HBV. RESULTS: Among 822 HIV infected patients, 29% were infected by HCV alone, 8% by HBV alone, and 4% by both HCV and HBV. The most frequent causes of death were liver disease (31% of cases) and AIDS (29%) among HIV-HCV co-infected patients, and AIDS (38%) and liver disease (22%) among HIV-HBV co-infected patients. Liver disease was a more frequent cause of death among patients co-infected by both HCV and HBV (44% of cases). Hepatocellular carcinoma was present in 15% of patients who died from liver disease, and was associated with HBV co-infection. Nearly half the patients who died from liver disease had more than 200 CD4/mm3. CONCLUSIONS: Liver disease is now a leading cause of death among HIV-HCV co-infected patients and is becoming an important cause of death among HIV-HBV co-infected patients. The risk of death from liver disease is highest in patients co-infected by both HCV and HBV.

Adult↗
PubMed2005

Dialyzer membrane permeability and survival in hemodialysis patients.

BACKGROUND: We previously showed that nutritional protein concentrations were predictive of outcome, whereas variables reflecting body composition and dialysis dose were not, in a 30-month prospective follow-up of 1,610 hemodialysis patients. Information on dialysis membrane and erythropoietin use had to be evaluated in an additional follow-up. METHODS: A subset of 650 patients from the initial cohort of 1,610 was analyzed for survival in a 2-year extension of follow-up. Detailed data were collected: demographics; cause of renal failure; time on dialysis therapy; type of membrane; erythropoietin treatment; body mass index (BMI); predialysis albumin, prealbumin, and bicarbonate levels; and outcome. Normalized protein catabolic rate (nPCR), dialysis adequacy, and lean body mass were computed from predialysis and postdialysis urea and creatinine values. RESULTS: Patient characteristics were age of 61 +/- 16 years, 58% men, BMI of 22.7 +/- 4.4 kg/m2 , time on dialysis therapy of 102 +/- 73 months, and 8.8% had diabetes. Dialysis parameters were duration of 247 +/- 31 minutes, Kt/V of 1.4 +/- 0.3, and nPCR of 1.2 +/- 0.3 g/kg/d. Albumin level was 3.73 +/- 0.53 g/dL (37.3 +/- 5.3 g/L), and prealbumin level was 31 +/- 8 mg/dL. The survival rate was 78.7% after 2 years. Survival was influenced by age, presence of diabetes, use of high-flux membrane, and serum albumin level, but not other variables, including Kt/V and prealbumin level. Two-year variations in values for urea, creatinine, and weight were predictive of survival in univariate, but not multivariate, analyses. CONCLUSION: In patients on dialysis therapy for a long period, better survival was observed when high-flux dialysis membranes were used.

Aged↗
PubMed2005

Opportunistic infections as causes of death in HIV-infected patients in the HAART era in France.

The objective of the study was to describe the underlying causes of death of HIV-infected patients in the HAART era and to focus on those related to opportunistic infection (OI), in a national multicentre study ('Mortalité 2000'). A total of 964 deaths were recorded and 924 cases were available for analysis. Underlying cause of death were AIDS-related (47%), viral hepatitis (11%), non-AIDS cancers (11%), cardiovascular diseases (7%) and others (11%). Among patients who died of AIDS events, 262 (27%) died of at least one OI. OIs reported at the time of death were Cytomegalovirus infection 67 times, Pneumocystis jiroveci pneumonia 56, disseminated Mycobacterium avium intracellulare infection 53 and cerebral toxoplasmosis 48. Compared to patients who died of other causes, patients who died of OIs were younger and more likely to be infected through heterosexual contact, in poor socioeconomic conditions, migrants, more recently diagnosed for HIV infection, and naive of antiretroviral therapy and OI prophylaxis. OIs are still a major cause of death in HIV-infected patient in the HAART era, especially among patients recently diagnosed for HIV infection and who do not have access to care, as well as in long term infected patients where prophylaxis should be revisited.

AIDS-Related Opportunistic Infections↗
PubMed2005

Letter. In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene.

In HIV-2 infection, many studies have reported a high frequency of selection of the Q151M mutation, but its impact on phenotypic susceptibility of HIV-2 isolates remains unclear. Four HIV-2 infected patients from the French ANRS HIV-2 cohort, with evidence of Q151M mutation in both plasma and available peripheral blood mononuclear cells (PBMCs) co-cultivated supernatants, were selected. In vitro phenotypic susceptibilities to different nucleoside reverse transcriptase inhibitors (NRTIs) were determined using a PBMC assay. In HIV-2 isolates, the Q151M mutation alone impacts only the phenotypic susceptibility to stavudine and abacavir. A decrease in susceptibility to all NRTIs was observed when Q151M was selected with V111I, a mutation of unknown impact on HIV-1 resistance. Clinical relevance of these phenotypic susceptibility results needs to be evaluated in HIV-2 treated patients.

Drug Resistance, Multiple, Viral↗
PubMed2004

Causes of death among human immunodeficiency virus (HIV)-infected adults in the era of potent antiretroviral therapy: emerging role of hepatitis and cancers, persistent role of AIDS.

BACKGROUND: In the era of highly active antiretroviral therapy (HAART) mortality has decreased substantially among human immunodeficiency virus (HIV)-infected people with access to HAART, but there are concerns regarding co-morbidities and adverse effects of HAART, which may impair vital prognosis. The Mortality 2000 study examined the causes of death in HIV-infected adults at a national level in France in the year 2000. METHODS: All French hospital wards known to be involved in the management of HIV infection were asked to notify prospectively the deaths that occurred in 2000 among HIV-infected adults. The causes of death were documented using a standardized questionnaire. RESULTS: The 185 participating wards notified 964 deaths. The main underlying causes of death were AIDS-related (47%, non-Hodgkin's lymphoma: 23%), viral hepatitis (11%, hepatitis C: 9%, hepatitis B: 2%), cancer not related to AIDS or hepatitis (11%), cardiovascular disease (7%), bacterial infections (6%), suicide (4%), and adverse effect of antiretroviral treatments (1%). Among AIDS-related deaths, HIV infection had been diagnosed recently in 20%. Smoking was recorded in 72% of cancer-related deaths and alcohol consumption in 54% of hepatitis-related deaths. Among non-HIV related deaths between 25 and 64 years, the proportion of infectious diseases (including HCV and HBV-related deaths) was higher in HIV-infected adults than in the general population. CONCLUSIONS: Improved strategies for detecting HIV infection before AIDS-defining complications occur are needed in the era of HAART. The prevention of non-AIDS related cancers, especially lung cancer, the management of non-Hodgkin's lymphoma, and of viral hepatitis are also important priorities.

Acquired Immunodeficiency Syndrome↗