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Biomedical subjects

S Blanche

Publications and source records attributed to S Blanche.

At least 37 records · Page 2Linked to original sources
PubMed2001

Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1.

CONTEXT: Zidovudine reduces maternal-infant transmission of human immunodeficiency virus 1 (HIV-1) infection by two thirds. Combination antiretroviral therapies are potentially more effective prevention. OBJECTIVES: To assess the safety of perinatal lamivudine-zidovudine therapy, especially in children, and its effects on viral load, acquisition of drug resistance, and maternal-infant transmission of HIV-1 in a nonbreastfeeding population. DESIGN AND SETTING: The Agence Nationale de Recherches sur le SIDA (ANRS) 075 Study, an open-label, nonrandomized intervention trial conducted in the context of an ongoing observational cohort study in 48 sites in France. PATIENTS: A total of 445 HIV-1-infected pregnant women were enrolled as the study cohort from February 1997 to September 1998; controls consisted of 899 pregnant women who had received zidovudine monotherapy in May 1994 to February 1997 as standard care. INTERVENTION: The study cohort received lamivudine in addition to the standard Pediatric AIDS Clinical Trial Group 076 Study zidovudine prophylaxis regimen. Lamivudine was initiated in women at 32 weeks' gestation through delivery at 150 mg twice per day orally; children received lamivudine, 2 mg/kg twice per day for 6 weeks. MAIN OUTCOME MEASURES: HIV-1 infection status and tolerance of therapy in children through age 18 months; maternal plasma HIV-1 RNA levels through 6 weeks after delivery. RESULTS: The transmission rate in the study group was 1.6% (7/437; 95% confidence interval [CI], 0.7%-3.3%). In a multivariable analysis, transmission in the study group was 5-fold lower than in controls. In the study group, maternal plasma HIV-1 RNA level was less than 500 copies/mL at delivery in 74%; the median decrease was 1.24 (range, -1.63 to 3.40) log(10) copies/mL. The M184V lamivudine resistance mutation was detected at 6 weeks after delivery in specimens from 52 of 132 women. The most frequent serious adverse events in children were neutropenia and anemia, requiring blood transfusion in 9 children and premature treatment discontinuation in 19. Two uninfected children died at age 1 year from neurologic complications related to mitochondrial dysfunction. CONCLUSIONS: Lamivudine-zidovudine may be effective in preventing maternal-infant HIV transmission. However, severe adverse effects and emergence of resistance to lamivudine occurred. Thus, the role of this combination therapy in this setting is as yet unclear, and further research involving a variety of strategies is needed to definitively ascertain its utility for preventing maternal-infant HIV transmission.

Anti-HIV Agents↗
PubMed2001

Tolerance of efavirenz in children.

OBJECTIVE: To extend the limited knowledge of efavirenz tolerance in children. METHOD: An observational study of 33 children given efavirenz combined with various others agents and followed in a single institution. RESULTS: Fifteen (42%) of the children presented at least one clinically discernable side effect, cutaneous (n = 5), nervous system (n = 10), or both (n = 2). Intolerance led to treatment interruption in seven children but the main symptom was transitory dizziness or other signs similar to those observed in adults. CONCLUSION: Early, often transient nervous system side effects require careful preparation with the child and his family to avoid premature and inadequate withdrawal from treatment.

Adolescent↗
PubMed2001

X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling.

The molecular basis of X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) has remained elusive. Here we report hypomorphic mutations in the gene IKBKG in 12 males with EDA-ID from 8 kindreds, and 2 patients with a related and hitherto unrecognized syndrome of EDA-ID with osteopetrosis and lymphoedema (OL-EDA-ID). Mutations in the coding region of IKBKG are associated with EDA-ID, and stop codon mutations, with OL-EDA-ID. IKBKG encodes NEMO, the regulatory subunit of the IKK (IkappaB kinase) complex, which is essential for NF-kappaB signaling. Germline loss-of-function mutations in IKBKG are lethal in male fetuses. We show that IKBKG mutations causing OL-EDA-ID and EDA-ID impair but do not abolish NF-kappaB signaling. We also show that the ectodysplasin receptor, DL, triggers NF-kappaB through the NEMO protein, indicating that EDA results from impaired NF-kappaB signaling. Finally, we show that abnormal immunity in OL-EDA-ID patients results from impaired cell responses to lipopolysaccharide, interleukin (IL)-1beta, IL-18, TNFalpha and CD154. We thus report for the first time that impaired but not abolished NF-kappaB signaling in humans results in two related syndromes that associate specific developmental and immunological defects.

Adolescent↗
PubMed2001

Patient-specific cytotoxic T-lymphocyte cross-recognition of naturally occurring variants of a human immunodeficiency virus type 1 (HIV-1) p24gag epitope by HIV-1-infected children.

We tested seven human immunodeficiency virus-infected children for their cytotoxic T-lymphocyte (CTL) activities towards the p24gag QASQEVKNW epitope and its nine variant sequences. Our data confirm that most, but not all, CTL responses are broadly cross-specific. For the first time, we show the high interpatient variability in cross-recognition of mutant CTL epitopes. These interindividual variations in the CTL response to the same epitope should be taken into account in the design and the evaluation of vaccines.

Child↗
PubMed2001

Cytotoxic T cells in AIDS colonic cryptosporidiosis.

BACKGROUND/AIMS: It is not known how enteric cryptosporidiosis induces severe intestinal impairment despite minimal invasion by the parasite. The aim of this study was to analyse the histological features and locally implicated immune cells in colonic biopsies of AIDS related cryptosporidiosis. PATIENTS/METHODS: Colonic biopsies from patients with AIDS related cryptosporidiosis (n = 10, group I), patients with AIDS but without intestinal infection (n = 9, group II), and human seronegative controls (n = 9, group III) were studied. Using immunohistochemistry the infiltrating mononuclear cells were analysed in both the epithelium and lamina propria for the expression of CD3, CD8, TiA1, granzyme B, and CD68 and for glandular expression of human major histocompatibility complex DR antigen (HLA-DR). RESULTS: Severe histological changes, resulting in abundant crypt epithelial apoptosis and inflammatory infiltrate in the lamina propria, were seen in all biopsies from group I. A significant increase of CD8+, TiA1+, and granzyme B+ T cells in the lamina propria and HLA-DR glandular expression was noted in group I compared with groups II and III. However, the number of intraepithelial lymphocytes, lamina propria CD3+ T cells, and macrophages was not significantly increased in cryptosporidiosis specimens compared with controls. CONCLUSION: Epithelial apoptosis mediated by granzyme B+ cytotoxic host T cells might play a major role in the development of colonic lesions in AIDS related cryptosporidiosis.

AIDS-Related Opportunistic Infections↗
PubMed2000

Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy.

BACKGROUND: The childhood-onset cerebral form of X-linked adrenoleukodystrophy, a demyelinating disorder of the central nervous system, leads to a vegetative state and death within 3-5 years once clinical symptoms are detectable. The hypothesis to be tested was whether bone-marrow transplantation can over an extended period of time halt the inexorable progressive demyelination and neurological deterioration. METHODS: 12 patients with childhood onset of cerebral X-linked adrenoleukodystrophy have been followed for 5-10 years after bone-marrow transplantation. Magnetic resonance imaging (MRI), neurological, neuropsychological, electrophysiological, and plasma very-long-chain fatty acid (VLCFA) measurements were used to evaluate the effect of this treatment. FINDINGS: MRI showed complete reversal of abnormalities in two patients and improvement in one. One patient showed no change from baseline to last follow-up. All eight patients who showed an initial period of continued demyelination stabilised and remained unchanged thereafter. Motor function remained normal or improved after bone-marrow transplantation in ten patients. Verbal intelligence remained within the normal range for 11 patients. Performance (non-verbal) abilities were improved or were stable in seven patients. Decline in performance abilities followed by stability occurred in five patients. Plasma VLCFA concentrations decreased by 55% and remained slightly above the upper limits of normal. INTERPRETATION: 5-10-year follow-up of 12 patients with childhood-onset cerebral X-linked adrenoleukodystrophy shows the long-term beneficial effect of bone marrow transplantation when the procedure is done at an early stage of the disease.

Adrenoleukodystrophy↗
PubMed2000

HIV-1-related encephalopathy in infants compared with children and adults. French Pediatric HIV Infection Study and the SEROCO Group.

OBJECTIVE: To characterize the specificities of HIV-1-related encephalopathy in children. METHODS: Comparison of patients from the French Perinatal Cohort of children born to HIV-1-infected mothers and followed from birth with the French SEROCO Cohort of adults with a known date of infection. Our study examines 1) the characteristics of encephalopathy with onset before 1 year, after 1 year, and in adults, and 2) the maternal and birth characteristics of infants who developed AIDS before 1 year and went on to develop either encephalopathy or opportunistic infection. RESULTS: The incidence of encephalopathy was higher in children than in adults during the first year (9.9% versus 0.3%) and intermediate during the second year (4.2% versus 0%) after infection but was similar thereafter (less than 1% per year in each group). The resulting cumulative incidence at 7 years postinfection reached 16% in children and 5% in adults. Encephalopathy that developed before 1 year 1) was more frequently an isolated symptom of AIDS, 2) was associated with a reduction of intrauterine brain growth, 3) was associated with a very low level of HIV-1 RNA in CSF, 4) occurred at a higher level of immunocompetence after taking into account the decrease in CD4 lymphocytes with age, and 5) was not prevented by zidovudine treatment during gestation. CONCLUSIONS: Early encephalopathy in infants has a different pathophysiologic mechanism than that occurring in children, which in turn shows similarities with that observed in adults. Early encephalopathy is probably related to the occurrence of pathologic events during late fetal life.

AIDS Dementia Complex↗
PubMed2000

[Lymphomas in children infected with HIV-1].

PURPOSE: To describe the features of lymphoma in human immunodeficiency virus (HIV)-infected children, their treatments and the outcome of patients. RESULTS: We analyzed seven HIV-infected children (four by mother-to-child transmission and three by transfusion) (25 months to 18.5 years old) with lymphoma (one Hodgkin's disease and six non-Hodgkin's lymphomas). All of them presented with a severe immunodepression and a high viral load. Five of six were high grade-B cell non-Hodgkin's lymphoma of large-cell histologies (immunoblastic or centroblastic). Five were extranodular disease and three were metastatic at diagnosis. Epstein-Barr virus was detected in four tumors. Five of seven received a multiagent chemotherapy. Toxicity was high. Treatment for the skin T lymphoma consisted of radiation therapy. Five children were complete responders (with survival three years, 2.5 years, 12, 18 and 18 months) and two died of progression of lymphoma (four and five months later). CONCLUSION: Incidence of lymphoma is increased in HIV-infected children. Anticancer chemotherapy regimens that include aggressive supportive care and concomitant antiretroviral therapy or immunotherapy may yield high survival rates.

Adolescent↗
PubMed2000

[Accidental HIV exposure of children through injury with discarded syringes].

Potential HIV exposure through injury with discarded syringes is a frequent event among children. Although no case of HIV infection has been reported so far in this context, an antiretroviral prophylaxis is generally proposed. Such treatment is extrapolated from consensus for management of exposed health care workers. Extremely low-risk and difficult administration of available drugs allows a case-by-case analysis and generally a less aggressive treatment.

Anti-HIV Agents↗
PubMed1999

CCR2B-64I chemokine receptor allele and mother-to-child HIV-1 transmission or disease progression in children. French pediatric HIV infection study group.

The beneficial role of a variant of the chemokine receptor CCR2B (CCR2B-641) in the evolution of HIV-1 infection in adults is still controversial. Furthermore, no studies have been performed in HIV-1-infected children. A multicenter and prospective study of 745 infants born to HIV-1-seropositive mothers was performed. The CCR2B-641 allele was studied in 525 non-African children among whom 523 had been previously genotyped for the CCR5delta32 allele and 220 African children. Of the 745 total, 376 children were infected and 369 were uninfected. In the complete population studied, the children homozygous for the CCR2B-64I allele and the heterozygous children were found distributed equally in the infected (respectively, 1.6% and 21%) and uninfected (respectively, 1.9% and 26.3%) groups (p < .22). Among 376 infected children, the incidence of stage C symptoms (U.S. Centers for Disease Control and Prevention [CDC] classification) or the progression of severe immune deficiency (CD4 <15%, CDC stage 3) was not significantly different in heterozygous infected children or children homozygous for the normal allele (p < .17 and p < .75, respectively). The same lack of protective effect was obtained when a separate analysis was performed in the non-African and African HIV-1-infected children.

Adult↗
PubMed1999

Frequent detection of HIV-1 in the gastric aspirates of neonates born to HIV-infected mothers.

OBJECTIVE: To evaluate the frequency and correlates of oral route exposure of infants born to HIV-1-infected women. METHODS: A multicenter study was performed within the prospective French Perinatal Cohort Study of mother-to-child HIV transmission. Oropharyngeal and gastric aspirates from 122 neonates were studied by reverse transcriptase (RT) polymerase chain reaction (PCR) for the presence of HIV-1, as well as for standard microbiology (Gram staining and culture). RESULTS: Aspirates from 101 neonates were analyzed by RT-PCR; 28% of these were positive for HIV RNA. Another 21 aspirates could not be tested because of PCR inhibition. The median concentration of HIV RNA in the positive aspirates was 126 copies/ml (range: 8-1270). Detection of HIV-1 in the aspirate was significantly related to high maternal plasma-viral load, presence of blood in the aspirate, positive Gram stain or culture, episiotomy or perineal lesions, and sexually transmitted infections during the pregnancy. Most of the mothers received zidovudine prophylaxis during pregnancy and delivery. Among the six infants who were infected with HIV, three had positive aspirates. Of the three assumed to have acquired the infection intrapartum, only one had an HIV RNA-positive aspirate. CONCLUSION: Exposure of the fetus to HIV via the oral route occurs frequently, even in the presence of zidovudine prophylaxis, and is likely to be one of the mechanisms of intrapartum transmission, but not the only one.

Adult↗