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Dominique Costagliola

Publications and source records attributed to Dominique Costagliola.

79 records · Page 5Linked to original sources

Time to AIDS from 1992 to 1999 in HIV-1-infected subjects with known date of infection.

To estimate the change in AIDS incubation time during three periods characterized by different availability of antiretroviral treatments, data from the French Hospital Database on HIV of 4702 HIV-1-positive subjects with a documented date of infection were analyzed. Times from seroconversion to AIDS were compared in three periods: period 1 from January 1992 to June 1995 (monotherapy); period 2 from July 1995 to June 1996 (dual therapy); and period 3 from July 1996 to June 1999 (triple therapy). Nonparametric survival analyses were performed to account for staggered entries in the database and during each period. From periods 1 to 3, antiretroviral treatments were initiated earlier after infection, more subjects were treated, and the nature of regimens changed (25.6% of subjects were treated with monotherapy in period 1, 34.6% were treated with dual therapy in period 2, and 53.4% were treated with triple therapy in period 3). Compared with period 1, the relative hazard (RH) of AIDS was 0.31 in period 3 (95% confidence interval [CI]: 0.24-0.39). When comparing period 3 with period 2, the RH of AIDS was 0.36 (CI: 0.29-0.45). Assuming a log normal distribution, the median time to AIDS was estimated as 8.0 years in period 1 (CI: 6.0-10.6), 9.8 years in period 2 (CI: 8.5, 11.2), and 20.0 years in period 3 (CI: 17.1-23.3). This lengthening in time to AIDS from 1992 to 1999 was particularly marked in the period after the introduction of triple therapy, including protease inhibitors.

Acquired Immunodeficiency Syndrome↗

Phenotypic or genotypic resistance testing for choosing antiretroviral therapy after treatment failure: a randomized trial.

OBJECTIVE: To assess the respective value of phenotype versus genotype versus standard of care for choosing antiretroviral therapy in patients failing protease inhibitor-containing regimens. METHODS: Patients with plasma HIV-1 RNA exceeding 1000 copies/ml were randomly allocated to phenotyping, genotyping, or standard of care. RESULTS: Five-hundred and forty-one patients were randomized, 190 to phenotyping, 192 to genotyping and 159 to standard of care. The baseline median CD4 cell count (280 x 106 cells/l), the plasma HIV-1 RNA level (4.3 log10 copies/ml), and the number of drugs previously received (n = 6) were similar in the three arms. More patients in the standard-of-care arm received at least three new drugs (55% versus 20% in the other arms; P < 0.001) and a regimen containing drugs from the three different classes. Plasma HIV-1 RNA was < 200 copies/ml at week 12 in 35% of patients in the phenotyping arm, 44% in the genotyping arm and 36% in the standard-of-care arm (phenotyping versus standard of care, P = 0.918; genotyping versus standard of care, P = 0.120). In a secondary analysis of 179 patients experiencing a first protease inhibitor failure, the percentage of patients achieving HIV-1 RNA < 200 copies/ml was significantly higher in the genotyping arm (65%) than in the phenotyping (45%) and the standard-of-care arms (45%) (genotyping versus standard of care, P = 0.022). CONCLUSIONS: Overall, resistance assays did not demonstrate benefit over standard of care. In patients with the most limited protease inhibitor experience, a significant benefit was observed in the genotyping arm.

Anti-HIV Agents↗

The incubation period of kuru.

BACKGROUND: Kuru is a transmissible spongiform encephalopathy that was identified in Papua New Guinea in the late 1950s. Several thousand cases of the disease occurred during a period of several decades. Epidemiologic investigations implicated ritual endocannibalistic funeral feasts as the likely route through which the infectious agent was spread. METHODS: We estimated the incubation period distribution of kuru using a back-calculation model and explored the relation among sex, age at infection, and incubation period. Key assumptions in the model were that the number of new kuru infections in a year was proportional to the number of kuru cases dying that year, and that the epidemic arose from a single case of sporadic Creutzfeldt-Jakob Disease occurring around 1900. RESULTS: The mean incubation period of kuru was estimated at between 10.3 and 13.2 years. Point estimates of the 90th percentile ranged from 21.1 to 27.0 years. The incubation period in females was estimated to be shorter than that in males. The shortest incubation periods were estimated in adult women, who may have been exposed to the largest doses of infectious material. CONCLUSIONS: Our findings suggest that the relatively young age of cases of variant Creutzfeldt-Jakob disease probably reflects increased levels of exposure in young people, rather than age-dependency in the incubation period.

Adolescent↗

Prevalence of IgG antibodies to human parvovirus B19 in haemophilia children treated with recombinant factor (F)VIII only or with at least one plasma-derived FVIII or FIX concentrate: results from the French haemophilia cohort.

Human parvovirus B19 (B19) has been transmitted by some brands of virally attenuated plasma-derived factor VIII (FVIII) or IX (FIX) concentrates. To quantify the differences of human parvovirus B19 risk transmission between albumin-stabilized recombinant factor and plasma-derived factor, we studied the prevalence of IgG antibodies to B19 (anti-B19) in 193 haemophiliac children between 1 and 6-years of age who had previously been treated with albumin-stabilized recombinant FVIII only (n = 104), and in children previously treated with solvent/detergent high-purity non-immunopurified and non-nanofiltered FVIII or IX concentrates (n = 89). Association between the prevalence of anti-B19 and the treatment group was analysed using multivariate logistic regression. Age, severity and type of haemophilia, number of cumulative days of exposure to factor VIII or IX, previous history of red blood cells or plasma transfusion were considered as potential confounding variables. A higher prevalence of anti-B19 was found in children previously treated with solvent/detergent high-purity non-immunopurified and non-nanofiltered FVIII or IX concentrates than in children treated with albumin- stabilized recombinant FVIII only (OR: 22.3; CI: 7.9-62.8), independently of the other factors studied.

Antibodies, Viral↗

Impact of stavudine phenotype and thymidine analogues mutations on viral response to stavudine plus lamivudine in ALTIS 2 ANRS trial.

OBJECTIVE: Stavudine-based antiretroviral combinations are less effective in zidovudine-experienced patients than in naive subjects and recently, mutations have been described to be associated to the use of both stavudine and zidovudine. In the ALTIS 2 trial, it was shown that a combination of stavudine and lamivudine is less effective in zidovudine-experienced patients than in naive patients. We conducted a retrospective genotypic and phenotypic resistance study (expressed as stavudine phenotypic index, calculated by dividing the inhibitory concentrations 50% [IC50] by the mean value of the sensitive viruses) to evaluate the factors associated with decrease in plasma HIV-1 RNA. DESIGN: Associations with continuous variables were studied using non-parametric Spearman correlation coefficients. Associations with categorical variables were studied using non-parametric Mann-Whitney tests. Multivariate stepwise regression analyses were used to determine independent prognostic factors of the virological response. RESULTS: At baseline, most of the subjects harboured zidovudine-associated mutations in plasma and peripheral blood mononuclear cells. Zidovudine and stavudine IC50 and IC50 were strongly associated with response. It appears that a cut-off of stavudine phenotypic index of 1.8-fold of IC50, much lower than the usually used value, could be clinically significant for response to stavudine. In the multivariate analysis, the stepwise model with the higher multiple correlation coefficient (R2 = 0.742) included the presence of a 215 Y/F mutation, the number of previously used nucleoside analogues and a resistant stavudine phenotype. CONCLUSION: These results argue for a phenotypic and genotypic cross resistance between stavudine and zidovudine. Modest increases of IC50 and IC50 for stavudine had an important impact on the virological response during the trial and plead for a new definition of the threshold value for stavudine phenotypic index.

Adult↗

The unrecognised French BSE epidemic.

In France, implementation of systematic screening programs in 2000, as a complement to the mandatory reporting of animals with clinical signs of BSE (passive surveillance), revealed certain limitations of the mandatory system. Indeed, systematic screening showed that some BSE cases were not detected by the clinical surveillance system, implying considerable BSE case under-reporting throughout the epidemic. As the most likely explanation for variant Creutzfeldt-Jakob disease (vCJD) is exposure to the aetiologic agent of BSE, it is essential to reconstruct the French BSE epidemic pattern accounting for this under-reporting. We estimated age- and year-specific incidence rates of BSE by using a back-calculation method. This approach relies on the principle that the number of clinical BSE cases is the consequence of the number of BSE-infected animals after a known incubation time, defined as the time between infection and clinical onset. We generalized this model to take into account epidemiological characteristics of BSE, such as French cattle mortality, BSE case reporting probability, and age-dependent susceptibility and/or exposure to the BSE agent. We confirmed that the average BSE incubation period is five years and that the peak risk of bovine infection occurs between 6 and 12 months of age. The results also showed that the proportion of underreporting is the most influential parameter in the model, and that BSE was substantially underreported until rapid tests were introduced. Indeed, only 103 BSE cases were detected by passive surveillance up to June 2000, while we estimated that there was 301 200 (95% confidence interval (CI) [27 600-837 600]) cattle infected by the BSE agent. Despite uncertainty over the beginning of the epidemic, we showed that the French BSE epidemic in the late 1980s was completely undetected, and only the second wave, after 1990, was observed.

Animals↗