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D Costagliola

Publications and source records attributed to D Costagliola.

At least 55 records · Page 3Linked to original sources
PubMed1999

Survival improvement of AIDS-related progressive multifocal leukoencephalopathy in the era of protease inhibitors. Clinical Epidemiology Group. French Hospital Database on HIV.

OBJECTIVE: To estimate the change in survival of patients with AIDS-related progressive multifocal leukoencephalopathy (PML), in relation to the introduction of protease inhibitors (PI). DESIGN: The French Hospital Database on HIV (FHDH) is a prospective cohort of 70 224 HIV-infected subjects. This study included the patients diagnosed with PML between 1 July 1995 and 30 June 1997. PML diagnosis was both presumptive and confirmed. We compared the survival probability according to the diagnosis period (period 1 or 2, before or after introduction of PI in France on 1 April 1996). Cox's model was used to calculate the relative hazards of death according to the antiretroviral regimen. RESULTS: The study included 246 patients, 109 diagnosed during period 1 and 137 during period 2. In all, 131 patients received an antiretroviral combination that included PI. By 31 December 1997, a total of 131 deaths had been reported. The probability of survival at 6 months for patients from period 2 was nearly twice as high as for patients from period 1 (60.5 versus 34.5%). In comparison with patients receiving no treatment, the risk of death in patients on combination therapy not including PI was reduced by 38% [relative hazard (RH) 0.62, 95% confidence interval (CI) (0.41; 0.95), P = 0.026] and in patients on combination therapy with PI, by 63% [RH 0.37, 95% CI (0.22; 0.64), P = 0.0004]. CONCLUSION: This study of a large cohort of patients diagnosed with PML (n = 246), provides evidence that a combination antiretroviral regimen, especially one including PI, confers marked survival benefits.

AIDS-Related Opportunistic Infections↗
PubMed1999

Visit-driven endpoints in randomized HIV/AIDS clinical trials: impact of missing data on treatment difference measured on summary statistics.

In randomized HIV/AIDS clinical trials, CD4 lymphocyte counts and plasma HIV-1 RNA measurements are often used as endpoints. The comparison between treatment groups is mainly based on a summary measure of outcome, so-called summary statistic. Such analyses are often complicated by missing data occurring as drop-outs. For the most currently used summary statistics in these trials, we examined the impact of missing data occurring as drop-outs on test size, in order to help choosing between these statistics. A simulation of missing-data patterns was performed, using HIV-1 plasma RNA measurements as the main endpoint, to compare the effect of three plausible informative patterns, depending on treatment group, and on baseline or current plasma viral load, on eight different summary statistics. Missing data resulted in test sizes over the nominal value for the area under the curve minus baseline, the least-squares slope, the slope estimated with use of a mixed effects linear model, assuming a linear trend over the entire study, the difference between baseline and nadir, and the difference between baseline and week 24. The difference between baseline and week 8 was an acceptable summary with respect to the test size, but did not reflect accurately the durability of the effect of treatment. Two criteria appeared as the best summary statistics: the slope estimated by a mixed effects model, with a change of slope after two weeks of treatment, and to a lesser degree, the area under the curve after carrying forward the last observation.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Discussion

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Journal Article↗
PubMed1999

Is the AIDS incubation time changing? A back-calculation approach.

Contradictory literature was recently published on possible changes in AIDS incubation time over the period 1978-1994. The purpose of this work was to test if a change in incubation time (shortening or lengthening) was observed in France, either globally or in specific transmission groups (homosexual-bisexual men, heterosexual subjects), using a back-calculation approach. An age dependent TSI model (time since infection), which took into account a temporary treatment effect and allowed us to test for a change in the incubation time, was applied to the French AIDS cases (Réseau National de Santé Publique). The EM algorithm was used to maximize the likelihood and the best model was selected on the basis of the likelihood ratio statistic. The analysis on all AIDS cases indicated a shortening of the AIDS incubation time estimated to begin in 1983 (95 per cent CI 1982-1984). This shortening of incubation time was also apparent when analysis was restricted to homosexual-bisexual men and to heterosexual subjects. This shortening corresponded to a median incubation time of 9.6 years (95 per cent CI 8.1-10.5) for people infected at 30 years of age in 1983, versus 12.7 years for people infected at 30 years of age before the change.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Timing of human immunodeficiency virus type 1 (HIV-1) transmission from mother to child: bayesian estimation using a mixture.

The timing of mother-to-child HIV transmission is not directly observable but influences the infected child's viral and immune status in the neonatal period. A hierarchical model was developed in a Bayesian framework to 'back-calculate' the timing of HIV-1 transmission from mother to child from the virological and immunological kinetics in the infected infant. Joint evolution of viral markers and immune response was modelled as a continuous time Markov process. The modelling of the period from infection to birth was based on a mixture of three distributions taking into account the various mother-to-child transmission pathways: In utero (early or late in gestation) and intrapartum (during the delivery process), integrating the fact that transmission is a continuum during the pregnancy. Gibbs sampling was used to estimate the marginal posterior distributions of the transition intensities between stages of HIV infection and those of the individual times from infection to birth. We applied our model to data on 135 perinatally HIV-1-infected children included in the French Prospective Study on Pediatric HIV infection. The model suggested that transmission occurred late in utero during the last month of pregnancy and that the day of delivery was a particularly critical time in HIV-1 transmission from mother to child. The paper ends with a discussion of model assumptions and a comparison with results obtained using a non-parametric method.

Antibodies, Viral↗
PubMed1999

Combined genotypes of CCR5, CCR2, SDF1, and HLA genes can predict the long-term nonprogressor status in human immunodeficiency virus-1-infected individuals.

Human immunodeficiency virus (HIV)-1-infected long-term nonprogressors (LT-NP) represent less than 5% of HIV-1-infected patients. In this work, we tried to understand whether combined genotypes of CCR5-triangle up32, CCR2-64I, SDF1-3'A and HLA alleles can predict the LT-NP status. Among the chemokine receptor genotypes, only the frequency of the CCR5-triangle up32 allele was significantly higher in LT-NP compared with the group of standard progressors. The predominant HLA alleles in LT-NP were HLA-A3, HLA-B14, HLA-B17, HLA-B27, HLA-DR6, and HLA-DR7. A combination of both HLA and chemokine receptor genotypes integrated in a multivariate logistic regression model showed that if a subject is heterozygous for CCR5-triangle up32 and homozygous for SDF1 wild type, his odds of being LT-NP are increased by 16-fold, by 47-fold when a HLA-B27 allele is present with HLA-DR6 absent, and by 47-fold also if at least three of the following alleles are present: HLA-A3, HLA-B14, HLA-B17, HLA-DR7. This model allowed a correct classification of 70% of LT-NPs and 81% of progressors, suggesting that the host's genetic background plays an important role in the evolution of HIV-1. The chemokine receptor and chemokine genes along with the HLA genotype can serve as predictors of HIV-1 outcome for classification of HIV-1-infected subjects as LT-NPs or progressors.

Adolescent↗
PubMed1999

In vitro endothelialization of PTFE vascular grafts: A comparison of various substrates, cell densities, and incubation times.

To establish the optimal conditions for achieving endothelial cell coverage of the luminal surfaces of small-caliber vascular grafts in vitro, the attachment of endothelial cells (ECs) cultured from human umbilical veins to polytetrafluoroethylene (PTFE) grafts was studied. Cell attachment and spreading were compared after PTFE grafts were (a) precoated with fibronectin (HFN), type I collagen, type IV collagen, plasma and fibrin with or without thrombin, singly or in combination; (b) seeded with cell densities varying from 0.5 x 10(5) to 6 x 10(5) cells/cm2; and (c) incubated at 30, 60, or 90 min. Cell coverage and spreading were assessed by means of scanning electron microscopy. Quantification of graft surface coverage was performed with computer-assisted image analysis. To determine optimal conditions of endothelialization among the 189 treatment combinations, analysis of variance was used. We conclude that a virtually confluent cell monolayer can be established on small-caliber PTFE grafts when precoated with fibrin glue or plasma, seeded with cell densities >/=4 x 10(5) cells/cm2, and incubated for 60 min. These parameters are compatible with an operating room vascular procedure.

Blood Vessel Prosthesis↗
PubMed1999

Direct HIV testing in blood donations: variation of the yield with detection threshold and pool size.

BACKGROUND: This study was designed to evaluate the potential yield of introducing nucleic acid amplification testing (NAT) in blood donation, according to the detection threshold and the pool size. STUDY DESIGN AND METHODS: A mathematical model of early HIV-1 population dynamics in blood has been developed and is used to predict the window period for NAT, according to the detection threshold and the pool size. The corresponding number of undetected, infected blood donations and the residual risk are estimated by using a previously published simulation model for the United States (9.96 million blood donations from regular donors, and an observed rate of HIV antibody-positive blood donations of 3.18/100,000) and for France (2.32 million blood donations, and a rate of antibody-positive donations of 0.9/100,000). RESULTS: The average window period from infection predicted by the mathematical model for NAT ranges from 8.4 to 15.6 days, according to the detection threshold and the pool size. The maximum yield of adding NAT to the current antibody tests is estimated at 14 donations for the United States and 2 for France. The maximum yield of adding NAT to the newly developed combined HIV antibody and p24 antigen tests is 7 donations for the United States and 1 for France. CONCLUSION: NAT at blood donation could reduce the HIV-1 window period to a minimal value of 8 days without pooling the blood samples, but the yield of NAT would be close to that of combined HIV antibody and p24 antigen tests for high values of the detection threshold and the pool size.

Blood Donors↗
PubMed1999

Status of long-term asymptomatic HIV-1 infection correlates with viral load but not with virus replication properties and cell tropism. French ALT Study Group.

Qualitative and quantitative virological parameters were investigated in 68 long-term nonprogressor (LTNP) HIV-1-infected patients and 9 slow-progressor controls. LTNP status was defined as an asymptomatic HIV infection for at least 8 years, a stability of CD4+ cell counts > or =600 cells/mm3 and no antiretroviral therapy. LTNP subjects exhibited a lower median plasma RNA load than controls (6,000 vs. 40,000 RNA copies/ ml) despite a wide range of values in both groups. When compared to the control group, LTNP subjects also exhibited a lower virus isolation rate (65% vs. 100%) and cell-associated viremia (0.75 vs. 56.8 number of infectious unit/ million cells) when CD8-depleted CD4+ cells were tested. By contrast, no major differences in virus replication properties or cell tropism were observed. After 1 year of follow-up, no major overall changes in the virological parameters was observed in the 50 LTNP subjects evaluated at this time. However, nine patients had started antiretroviral therapy, and six others had increased viral loads. Despite the progression observed during the first year of follow-up, the hypothesis that there is a specific subgroup of LTNP patients who will not develop disease cannot be ruled out as yet.

CD4-Positive T-Lymphocytes↗
PubMed1998

Efficacy and tolerability of stavudine plus lamivudine in treatment-naive and treatment-experienced patients with HIV-1 infection.

BACKGROUND: A combination of two nucleoside analogues is currently the core of any antiretroviral regimen for HIV-1 infection. Stavudine plus lamivudine has shown an additive effect in vitro, as well as an absence of overlapping toxicity and cross-resistance. OBJECTIVE: To evaluate the antiviral efficacy of stavudine plus lamivudine in treatment-naive patients and in patients previously treated with other nucleoside reverse transcriptase inhibitors. DESIGN: Prospective, open-label pilot study. SETTING: Three urban clinical centers in Paris. PATIENTS: 83 patients with CD4+ cell counts between 50 and 400 cells/mm3 (42 treatment-naive and 41 treatment-experienced patients). INTERVENTIONS: Stavudine, 40 mg twice daily (30 mg twice daily in patients with a body weight < or = 60 kg), and lamivudine, 150 mg twice daily. MEASUREMENTS: Primary end points for efficacy included changes in plasma viral load and CD4+ cell count at 24 weeks compared with baseline. RESULTS: Therapy with stavudine plus lamivudine resulted in a median decrease of 1.66 log10 (10(1.66)) (range, -3.04 to -0.79 log10) in plasma HIV-1 RNA; the median increase in CD4+ cell count was 108 cells/mm3 (range, -58 to 406 cells/mm3) at week 24 in treatment-naive patients. In treatment-experienced patients, the median reduction in plasma HIV-1 RNA was 0.55 log10 (range, -2.86 to 0.52 log10), and the median increase in CD4+ cell count was 46 cells/mm3 (range, -188 to 311 cells/mm3). The percentages of patients with less than 3000 HIV-1 RNA copies/mL and less than 400 copies/mL at 24 weeks were, respectively, 57% (95% CI, 41% to 72%) and 26% (CI, 12% to 40%) among treatment-naive patients and 22% (CI, 10% to 38%) and 5% (CI, 1% to 17%) among treatment-experienced patients. Of 82 patients, 14 (17%) experienced grade 3 or 4 toxicity and 2 discontinued therapy because of intolerance toward treatment. CONCLUSION: Stavudine plus lamivudine seems to have a potent antiviral effect in treatment-naive and treatment-experienced patients. No major drug-limiting toxicity was found. This two-nucleoside combination should be considered in multidrug therapy for HIV.

Adult↗
PubMed1998

Early regression of cervical lesions in HIV-seropositive women receiving highly active antiretroviral therapy.

OBJECTIVE: Advanced HIV disease is associated with a high prevalence of cervical squamous intra-epithelial lesions (SIL) and of infection with oncogenic human papillomavirus (HPV) genotypes. Triple-combination antiretroviral therapy results in decreased plasma HIV viral load, increased CD4 cell counts and partial restoration of immune functions in patients with severe HIV disease. This study investigated the outcome of SIL in HIV-seropositive women undergoing triple combination antiretroviral treatment. METHODS: Forty-nine women who started triple-combination antiretroviral therapy, including a protease inhibitor, were examined prior to and after a median 5-month treatment. We collected cytological, colposcopic and histologic data and assessed the presence of HPV DNA in cervical smears by PCR and Southern blot hybridization (SBH). RESULTS: The prevalence of SIL decreased from 69 to 53% during follow-up (P < 0.0001). Among 13 women who initially presented with high-grade SIL, conversion to lower grade was observed in two women and a full regression to normality was observed in one. Cytology also returned to normality in nine out of 21 women who initially presented with low-grade SIL. The high prevalence of HPV infection as detected by SBH and PCR was similar at the first and second examinations and the same high-risk viral genotypes were identified at both examinations in all infected patients but one. There was a higher increase in absolute CD4 cells in the subgroup of patients whose lesions regressed (99 versus 50 x 10(6)/l, P=0.03). CONCLUSION: Our observations demonstrate that active antiretroviral therapy may result in a reduced prevalence of cervical squamous intra-epithelial lesions despite the absence of clearance of HPV infection.

Adult↗
PubMed1998

Serum ferritin, desferrioxamine, and evolution of HIV-1 infection in thalassemic patients.

To study the respective roles of mean serum ferritin level and the mean desferrioxamine (DFX) dose on progression of HIV-1 infection, data from 49 HIV-seropositive thalassemic patients were analyzed using a Cox proportional hazards model including known confounding variables. Nine years after seroconversion, 10% of those who had been prescribed >40 mg/kg of DFX daily had entered stage IV versus 39% of those who had been prescribed a lower dose. Patients with ferritin level >1935 g/L entered stage IV more rapidly than those with a lower level (31% versus 16%). In multivariate analysis, the ferritin level was found to be an independent predictor of progression of HIV disease, whereas the mean daily dose of DFX was not. Similar results were obtained when death was the endpoint. Our results support a hypothesis that was recently expressed, that iron overload could be associated with a more rapid progression of HIV-1 infection.

Child↗