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Biomedical subjects

L Mandelbrot

Publications and source records attributed to L Mandelbrot.

At least 19 recordsLinked to original sources
PubMed2000

Increased risk of cervical disease among human immunodeficiency virus-infected women with severe immunosuppression and high human papillomavirus load(1).

OBJECTIVE: To investigate human papillomavirus (HPV) genotypes, HPV DNA load, and behavioral and sociodemographic factors in a series of human immunodeficiency virus (HIV)-seropositive women, and to correlate HPV infection with cervical disease according to immune status. METHODS: Three hundred seven HIV-seropositive women were tested for the presence of HPV DNA by polymerase chain reaction (PCR) and Southern blot hybridization. Cervical disease was assessed using Papanicolaou smears, colposcopy, and biopsies when necessary. Various risk factors for cervical intraepithelial neoplasia (CIN) were tested using multiple logistic regression analysis. RESULTS: Cervical disease was diagnosed in 83 (27.0%) of 307 women and HPV infection in 162 (52.8%). High HPV load (as detectable by Southern blot hybridization) was found in 90 (55.6%) of the 162 infected women. Potentially oncogenic or related genotypes were detected in 74 (82.2%) of these 90 cases. High-load HPV infection was twice as frequent in severely immunosuppressed women (CD4 cell count less than 200/microL) as in women with higher CD4 cell counts (P =.002). High-load HPV infection was associated with a high risk of cervical disease (adjusted odds ratio [OR] 16.8; 95% confidence interval [CI] 7.0, 40.3). The risk among severely immunosuppressed women was ten times greater than that among women with CD4 cell counts of at least 200/microL. Low-load HPV infection (detected by PCR only) was a risk factor for CIN in severely immunosuppressed women only (adjusted OR 7.4; 95% CI 1.3, 43.0). CONCLUSION: Immunosuppression favors cervical high-load HPV infection with oncogenic genotypes and its clinical expression in HIV-seropositive women.

AIDS-Related Opportunistic Infections↗
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↗
PubMed1999

[Pregnancy and HIV].

The issues raised have evolved over the last few years. The rate of mother-to-child transmission has decreased, mostly as a consequence of antiretroviral therapies. However, these drugs can have toxicity such as mitochondrial diseases in the infant, whose incidence and long term consequences are still unknown. The choice of therapy should be based on an estimate of benefit on risk on a case-to-case basis. If the patient requires an effective antiretroviral combination, it should not be withheld because of the pregnancy. If the mother does not require therapy for her own health, prevention of vertical transmission is based on zidovudine monotherapy beginning in the third trimester, which is most effective when combined with elective caesarean delivery. Interdisciplinary care must include clear information in a climate of dialogue with the mother.

Anti-HIV Agents↗
PubMed1999

Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues.

BACKGROUND: Zidovudine is commonly administered during pregnancy to prevent mother-to-child HIV-1 transmission. We investigated mitochondrial toxic effects in children exposed to zidovudine in utero and after birth. METHODS: We analysed observations of a trial of tolerance of combined zidovudine and lamivudine and preliminary results of a continuing retrospective analysis of clinical and biological symptoms of mitochondrial dysfunction in children born to HIV-1-infected women in France. Mitochondrial dysfunction was studied by spectrophotometry and polarography of respiratory-chain complexes in various tissues. FINDINGS: Eight children had mitochondrial dysfunction. Five, of whom two died, presented with delayed neurological symptoms and three were symptom-free but had severe biological or neurological abnormalities. Four of these children had been exposed to combined zidovudine and lamivudine, and four to zidovudine alone. No child was infected with HIV-1. All children had abnormally low absolute or relative activities of respiratory-chain complexes I, IV, or both months or years after the end of antiretroviral treatment. No mutation currently associated with constitutional disease was detected in any patient. INTERPRETATION: Our findings support the hypothesis of a link between mitochondrial dysfunction and the perinatal administration of prophylactic nucleoside analogues. Current recommendations for zidovudine monotherapy should however be maintained. Further assessment of the toxic effects of these drugs is required.

Acidosis, Lactic↗
PubMed1999

The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1--a meta-analysis of 15 prospective cohort studies.

BACKGROUND: To evaluate the relation between elective cesarean section and vertical transmission of human immunodeficiency virus type 1 (HIV-1), we performed a meta-analysis using data on individual patients from 15 prospective cohort studies. METHODS: North American and European studies of at least 100 mother-child pairs were included in the meta-analysis. Uniform definitions of modes of delivery were used. Elective cesarean sections were defined as those performed before onset of labor and rupture of membranes. Multivariate logistic-regression analysis was used to adjust for other factors known to be associated with vertical transmission. RESULTS: The primary analysis included data on 8533 mother-child pairs. After adjustment for receipt of antiretroviral therapy, maternal stage of disease, and infant birth weight, the likelihood of vertical transmission of HIV-1 was decreased by approximately 50 percent with elective cesarean section, as compared with other modes of delivery (adjusted odds ratio, 0.43; 95 percent confidence interval, 0.33 to 0.56). The results were similar when the study population was limited to those with rupture of membranes shortly before delivery. The likelihood of transmission was reduced by approximately 87 percent with both elective cesarean section and receipt of antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, as compared with other modes of delivery and the absence of therapy (adjusted odds ratio, 0.13; 95 percent confidence interval, 0.09 to 0.19). Among mother-child pairs receiving antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, rates of vertical transmission were 2.0 percent among the 196 mothers who underwent elective cesarean section and 7.3 percent among the 1255 mothers with other modes of delivery. CONCLUSIONS: The results of this meta-analysis suggest that elective cesarean section reduces the risk of transmission of HIV-1 from mother to child independently of the effects of treatment with zidovudine.

Anti-HIV Agents↗
PubMed1999

6-month efficacy, tolerance, and acceptability of a short regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Côte d'Ivoire and Burkina Faso: a double-blind placebo-controlled multicentre trial. DITRAME Study Group. DIminution de la Transmission Mère-Enfant.

BACKGROUND: Zidovudine reduces the rate of vertical transmission of HIV in non-breastfed populations. We assessed the acceptability, tolerance, and 6-month efficacy of a short regimen of oral zidovudine in African populations practising breastfeeding. METHODS: A randomised double-blind placebo-controlled trial was carried out in public clinics of Abidjan, Côte d'Ivoire, and Bobo-Dioulasso, Burkina Faso. Eligible participants were women aged 18 years or older, who had confirmed HIV-1 infection and pregnancy of 36-38 weeks duration, and who gave written informed consent. Exclusion criteria were severe anaemia, neutropenia, abnormal liver function, and sickle-cell disease. Women were randomly assigned zidovudine (n=214; 300 mg twice daily until labour, 600 mg at beginning of labour, and 300 mg twice daily for 7 days post partum) or matching placebo (n=217). The primary outcome was the diagnosis of HIV-1 infection in the infant on the basis of sequential DNA PCR tests at days 1-8, 45, 90, and 180. We compared the probability of infection at a given age in the two groups. Analyses were by intention to treat. FINDINGS: Women were enrolled between September, 1995, and February, 1998, when enrolment to the placebo group was stopped. Analysis was based on 421 women and 400 lifeborn infants. Baseline demographic, clinical, and laboratory characteristics were similar in the two groups. The Kaplan-Meier probability of HIV infection in the infant at 6 months was 18.0% in the zidovudine group (n=192) and 27.5% in the placebo group (n=197; relative efficacy 0.38 [95% CI 0.05-0.60]; p=0.027). Adjustment for centre, period of recruitment, mode of delivery, maternal CD4-cell count, duration of labour, prolonged rupture of membranes, and duration of breastfeeding did not change the treatment effect. The proportions of women taking more than 80% of the planned maximum dose were 75% before delivery, 81% during labour, and 83% post partum, without statistical difference between the groups. No major adverse biological or clinical event was reported in excess among women and children of the zidovudine group. INTERPRETATION: A short course of oral zidovudine given during the peripartum period is well accepted and well tolerated, and provides a 38% reduction in early vertical transmission of HIV-1 infection despite breastfeeding.

Adolescent↗
PubMed1999

Risk factors for perinatal human immunodeficiency virus transmission in patients receiving zidovudine prophylaxis. Pediatric AIDS Clinical Trials Group protocol 076 Study Group.

OBJECTIVE: To identify modifiable obstetric factors associated with the failure of zidovudine chemoprophylaxis to prevent perinatal human immunodeficiency virus type 1 (HIV-1) transmission. METHODS: We analyzed data from Pediatric AIDS Clinical Trials Group protocol 076, a randomized, double-masked, placebo-controlled trial that demonstrated that a zidovudine regimen could prevent perinatal HIV-1 transmission. We estimated the zidovudine treatment effect using the relative reduction in transmission risk among women randomized to treatment with zidovudine compared with women randomized to receive placebo. Univariate and multivariate statistical analyses were used to assess whether the treatment effect differed in magnitude according to potential antepartum or intrapartum risk factors. RESULTS: In the univariate analysis, the zidovudine treatment effect was found to differ significantly in magnitude according to quartile of maternal weight at the time of study entry (interaction test, P = .03); among women in the heaviest-weight quartile (weight more than 82 kg), there was a 26% relative reduction in transmission risk, compared with a 79% relative reduction among the other three quartiles (interaction test, P = .05). In the zidovudine treatment group, women who transmitted HIV-1 were significantly more likely than nontransmitters to have had antepartum procedures or conditions associated with increased risk of fetal exposure to maternal blood or cervicovaginal secretions (43% compared with 19%, P = .04). In the multivariate analysis, adjustment for the plasma HIV-1 RNA level and CD4+ cell percentage did not eliminate the differential treatment effect according to these factors. CONCLUSION: High maternal weight and conditions associated with fetal exposure to maternal blood or cervicovaginal secretions may diminish the efficacy of zidovudine chemoprophylaxis.

Anti-HIV Agents↗
PubMed1999

Safety and acceptability of vaginal disinfection with benzalkonium chloride in HIV infected pregnant women in west Africa: ANRS 049b phase II randomized, double blinded placebo controlled trial. DITRAME Study Group.

OBJECTIVES: To study the tolerance and acceptability in Africa of a perinatal intervention to prevent vertical HIV transmission using benzalkonium chloride disinfection. DESIGN: A randomized, double blinded phase II trial. SETTING: Prenatal care units in Abidjan (Côte d'Ivoire) and Bobo-Dioulasso (Burkina Faso). PATIENTS: Women accepting testing and counselling who were seropositive for HIV-1 and under 37 weeks of pregnancy were eligible. A total of 108 women (54 in each group) enrolled from November 1996 to April 1997, with their informed consent. INTERVENTION: Women self administered daily a vaginal suppository of 1% benzalkonium chloride or matched placebo from 36 weeks of pregnancy, and a single intrapartum dose. The neonate was bathed with 1% benzalkonium chloride solution or placebo within 30 minutes after birth. MAIN OUTCOME MEASURES: Adverse events were recorded weekly, with a questionnaire and speculum examination in women through delivery, and examination of the neonate through day 30. The incidence of genital signs and symptoms in the women and cutaneous or ophthalmological events in newborns were compared between groups on an intent to treat basis. RESULTS: The median duration of prepartum treatment was 21 days (range 0-87 days). Compliance was 87% for prepartum and 69% for intrapartum treatment, and 88% for the neonatal bath, without differences between the two groups. In women, the most frequent event was leucorrhoea; the incidence of adverse events did not differ between treatment groups. In children, the incidence of dermatitis and conjunctivitis did not differ between the benzalkonium chloride and placebo groups (p = 0.16 and p = 0.29, respectively). CONCLUSION: Vaginal disinfection with benzalkonium chloride is a feasible and well tolerated intervention in west Africa. Its efficacy in preventing vertical HIV transmission remains to be demonstrated.

Administration, Intravaginal↗
PubMed1999

HIV infection among pregnant women in Bobo-Dioulasso, Burkina Faso: comparison of voluntary and blinded seroprevalence estimates.

The objective of our study was to estimate the prevalence of HIV infection among pregnant women in Bobo-Dioulasso (Burkina Faso) according to 2 survey methods. Unlinked anonymous HIV screening was performed among women attending 2 antenatal clinics. Voluntary and confidential HIV counselling and testing were offered to women attending 2 other antenatal clinics in the same time period, September-October 1996. Voluntary HIV testing was performed in the context of a clinical trial on mother-to-child transmission of HIV (ANRS 049 clinical trial) with an acceptance rate of HIV testing of 93%. The first survey recruited 200 women and the second, 424. The mean age (24.6 years vs 24.8 years) and the mean number of pregnancies (3.1 vs 3.3) of women were comparable, in the 2 studies (P=0.69 and P=0.26, respectively). Prevalence of HIV infection in the blinded survey was estimated at 10.0% (95% confidence interval (CI): 6.4-15.2), while it was 9.4% (95% CI: 6.9-12.7) in the voluntary HIV screening programme. These 2 estimates were not statistically different (P=0.82). In the voluntary screening study, the prevalence of HIV infection was significantly different between age groups 15-24 years and 25-49 years (13.9% vs 4.5%, P < 0.001). In the age group 25-49 years, the prevalence of HIV infection estimated in the blinded study and in the voluntary screening study were significantly different (10.5% vs 4.5%, P=0.04) suggesting a potential participation bias among pregnant women of older age in the voluntary, confidential HIV screening group. In conclusion, for the purpose of HIV surveillance, the most reliable method for HIV prevalence remains the unlinked, anonymous testing.

Adult↗
PubMed1999

Anaemia during pregnancy in Burkina Faso, west Africa, 1995-96: prevalence and associated factors. DITRAME Study Group.

We report the results of a cross-sectional study carried out in 1995-96 on anaemia in pregnant women who were attending two antenatal clinics in Bobo-Dioulasso, Burkina Faso, as part of a research programme including a clinical trial of zidovudine (ZDV) in pregnancy (ANRS 049 Clinical Trial). For women infected with human immunodeficiency virus (HIV) in Africa, anaemia is of particular concern when considering the use of ZDV to decrease mother-to-child transmission of HIV. The objectives were to determine the prevalence of and risk factors for maternal anaemia in the study population, and the effect of HIV infection on the severity of maternal anaemia. HIV counselling and testing were offered to all women, and haemograms were determined for those women who consented to serological testing. Haemoglobin (Hb) levels were available for 2308 of the 2667 women who accepted HIV testing. The prevalence of HIV infection was 9.7% (95% confidence interval (CI): 8.6-10.8%). The overall prevalence of anaemia during pregnancy (Hb level < 11 g/dl) was 66% (95% CI: 64-68%). The prevalence of mild (10 g/dl < or = Hb < 11 g/dl), moderate (7 g/dl < or = Hb < 10 g/dl) and severe (Hb < 7 g/dl) anaemia was 30.8%, 33.5% and 1.7%, respectively. The prevalence of anaemia was 78.4% in HIV-infected women versus 64.7% in HIV-seronegative women (P < 0.001). Although the relative risk of HIV-seropositivity increased with the severity of anaemia, no significant association was found between degree of anaemia and HIV serostatus among the study women with anaemia. Logistic regression analysis showed that anaemia was significantly and independently related to HIV infection, advanced gestational age, and low socioeconomic status. This study confirms the high prevalence of anaemia during pregnancy in Burkina Faso. Antenatal care in this population must include iron supplementation. Although HIV-infected women had a higher prevalence of anaemia, severe anaemia was infrequent, possibly because few women were in the advanced stage of HIV disease. A short course regimen of ZDV should be well tolerated in this population.

Adolescent↗
PubMed1998

Attitude of pregnant women towards HIV testing in Abidjan, Côte d'Ivoire and Bobo-Dioulasso, Burkina Faso. DITRAME Study Group (ANRS 049 Clinical Trial). Diminution de la Transmission Mère Enfant du VIH. Agence Nationale de Recherches sur le SIDA.

OBJECTIVE: To evaluate the attitude of pregnant women towards HIV testing in two cities of West Africa: Abidjan, Côte d'Ivoire and Bobo-Dioulasso, Burkina Faso. METHODS: In the context of a clinical trial to prevent HIV vertical transmission, HIV counselling and testing was offered systematically to women attending antenatal clinics. Informed consent was obtained and test results were given anonymously. Multiple logistic regression was performed to identify factors associated with refusal for testing and failure to return for test results. RESULTS: A total of 9724 pregnant women were interviewed from January 1995 to September 1996. In Abidjan (n=5766) and Bobo-Dioulasso (n=3958), 78 and 92.4% of the women consented to HIV testing, respectively, and 58.4 and 81.8% of them returned for the test results disclosure, respectively. In the two sites, the counsellors themselves and high educational level of the women appeared to be related to refusal of the test, whereas last trimester gestation was associated with failure to return for test results. In Abidjan, foreigners and employees were more likely to refuse testing, and HIV-infected women were three times less likely to return for results than uninfected women. CONCLUSION: Future implementation of interventions to reduce vertical transmission of HIV that require antenatal HIV testing and counselling will have to solve issue of acceptability of HIV testing by pregnant women.

Burkina Faso↗
PubMed1998

Perinatal HIV-1 transmission: interaction between zidovudine prophylaxis and mode of delivery in the French Perinatal Cohort.

CONTEXT: It is unclear whether elective cesarean delivery may have a protective effect against the transmission of human immunodeficiency virus 1 (HIV-1). OBJECTIVE: To investigate whether mode of delivery has an impact on perinatal HIV-1 transmission in the presence of zidovudine prophylaxis. DESIGN: A prospective cohort study. SETTING: The 85 perinatal centers in the French Perinatal Cohort, from 1985 to 1996. PATIENTS: A total of 2834 singleton children born to mothers with HIV-1 infection. MAIN OUTCOME MEASURE: Human immunodeficiency virus 1 infection of the infant. RESULTS: No zidovudine was used in 1917 pregnancies and zidovudine prophylaxis was used in 902 pregnancies. Cesarean deliveries were performed in 10.9% on an emergent basis and in 8.3% electively, prior to labor or membrane rupture. In 1917 mothers who did not receive zidovudine, of 1877 with information on mode of delivery, 17.2% transmitted HIV-1 to their child. Risk factors statistically significantly associated with transmission were maternal p24 antigenemia, cervicovaginal infections during pregnancy, amniotic fluid color, and rupture of membranes 4 hours or more before delivery. Mode of delivery was not related to transmission. In 902 mothers receiving zidovudine, transmission was 6.4% in 872 with information on mode of delivery, and elective cesarean delivery (n = 133) was associated with a lower transmission rate than emergent cesarean or vaginal delivery (0.8%, 11.4%, and 6.6%, respectively; P=.002). In a multivariate analysis of all mother-child pairs, including obstetrical risk factors, maternal p24 antigenemia, and zidovudine prophylaxis, interaction between mode of delivery and zidovudine prophylaxis was significant (P=.007). In the multivariate analysis of pregnancies with zidovudine prophylaxis, factors related to transmission rate were maternal p24 antigenemia, amniotic fluid color, and mode of delivery. Adjusted odds ratios (95% confidence intervals) were 1.6 (0.7-3.6) for emergent cesarean delivery and 0.2 (0.0-0.9) for elective cesarean delivery (P = .04) in comparison with vaginal delivery. CONCLUSIONS: We observed an interaction between zidovudine prophylaxis and elective cesarean delivery in decreasing transmission of HIV-1 from mother to child. This observation may have clinical implications for prevention.

Anti-HIV Agents↗
PubMed1998

Prenatal diagnosis of an 8p23.1 deletion in a fetus with a diaphragmatic hernia and review of the literature.

The prenatal diagnosis of an 8p23.1 deletion is reported. The diagnosis was ascertained at 22 weeks of gestation because of the discovery of a diaphragmatic hernia at ultrasound. Following cytogenetic studies and counselling, the pregnancy was terminated. An autopsy confirmed the presence of a diaphragmatic hernia and revealed also the existence of an atrio-ventricular canal (AVC) and an atrial septal defect (ASD). The clinical features of this antenatally diagnosed case are compared with those observed in 16 previously reported cases with an identical deletion of the short arm of chromosome 8. This suggests that a deletion 8p23.1 should be considered whenever a diaphragmatic hernia and/or an AVC is detected on ultrasound.

Adult↗
PubMed1998

Vertical transmission of viral infections.

A variety of congenital viral infections are responsible for a large proportion of the mortality and morbidity in infancy and childhood. Vertical transmission may occur during primary maternal infection or during chronic or recurrent infection, with different implications for counselling and testing in pregnancy. Strategies for the diagnosis and prevention of mother-to-child transmission differ according to the timing and mechanisms involved. As demonstrated by hepatitis B research in the past and human immunodeficiency virus today, multicenter cohort studies and clinical trials are a key to developing effective interventions.

Cytomegalovirus Infections↗
PubMed1998

A randomised trial of mode of delivery in women infected with the human immunodeficiency virus.

OBJECTIVE: During the pilot phase of a trial to evaluate the effectiveness of caesarean section delivery compared with vaginal delivery in reducing mother-to-child transmission of human immunodeficiency virus (HIV) infection, the feasibility of randomisation to mode of delivery was assessed. DESIGN: At 36 weeks of pregnancy, women infected with HIV were randomly allocated to either caesarean section delivery at 38 weeks or vaginal delivery. Information was also collected on the reasons why women were not enrolled, either because they refused or had a contraindication. SETTING: Fifty-one centres in six European countries. POPULATION: Pregnant women with confirmed HIV-1 infection. MAIN OUTCOME MEASURES: Randomisation. RESULTS: Three-hundred and thirty-nine women had been randomised by the end of 1996, the large majority from Italy (n = 250) and France (n = 54), with 22 from South Africa, three from Sweden, nine from Barcelona and one from London. A further 150 women were eligible but had not been randomised. Forty-eight women (14%) were not delivered according to the arm to which they were randomised; the majority (n = 44) were changed from vaginal to caesarean section delivery. There is wide variation between European countries in the acceptability and adherence to the mode of delivery trial. CONCLUSION: The pilot phase of this trial has shown that in some settings randomisation to mode of delivery is feasible and acceptable, but that in other settings clinicians and pregnant women are more reluctant to be randomised. Pending further information on transmission rates and accrual, enrollment into the trial continues.

Cesarean Section↗