Therapeutic and other interventions to reduce the risk of mother-to-child transmission of HIV-1 in Europe

OBJECTIVES: To document policies regarding the use of interventions to reduce risk of vertical transmission of human immunodeficiency virus (HIV) and assess the extent of changes since 1994. DESIGN: A postal questionnaire survey and data from the European Collaborative Study (ECS), a prospective multi-centre cohort study. SETTING: Fifty-four obstetric centres in 16 European countries. SAMPLE: A questionnaire response from 54 obstetricians; 669 deliveries to HIV-infected women enrolled in the ECS from 1994 to 1997. MAIN OUTCOME MEASURES: Use of zidovudine during pregnancy, at delivery and to the neonate; caesarean section delivery rates; vaginal lavage; avoidance of breastfeeding; vertical transmission rate. RESULTS: Zidovudine therapy to reduce vertical transmission is now widespread in Europe and routine in all but one centre surveyed, although regimens vary. In 11 (26%) centres elective caesarean section is offered to all HIV-infected women and a further nine (21%) have a policy of routine vaginal lavage. In all centres HIV-infected women are advised to avoid breastfeeding. In the ECS there has been a significant temporal decline in the vertical transmission rate with an increase in zidovudine use. More than 90% of women in the ECS who were delivered in 1997 received one or more components of zidovudine therapy; the rate of vertical transmission is 9% where zidovudine has been used, compared with 15% without use of zidovudine. CONCLUSIONS: Although the use of zidovudine to reduce vertical transmission is increasing in Europe and, with the avoidance of breastfeeding, is associated with a decline in vertical transmission, the success of these interventions will be limited by the uptake of antenatal screening

Identifying predictors of interferon-gamma release assay results in pediatric latent tuberculosis: a protective role of BCG?

Rationale: Interferon-gamma release assays are widely used to diagnose latent infection with Mycobacterium tuberculosis in adults, but their performance in children remains incompletely evaluated to date. Objectives: To investigate factors influencing results of interferon gamma release assays in children using a large European dataset. Methods: The Pediatric Tuberculosis Network European Trials group pooled and analysed data from five sites across Europe comprising 1128 children who were all investigated for latent tuberculosis infection by using TST and at least one interferon-gamma release assay. Multi-variate analyses examined age, Bacille Calmette-Guérin (BCG) vaccination status, and gender as predictor variables of results. Subgroup analyses included children who were household contacts. Measurements and results:1,093 children had a Quantiferon Gold In-Tube and 382 had a T-SPOT.TB interferon gamma release assay. Age was positively correlated with a positive blood result (Quantiferon Gold In-Tube: OR=1.08 per year increasing age, p<0.0001; T-SPOT.TB: OR=1.14 per year increasing age, p<0.001). 5.5% of children with a tuberculin skin test result <5mm, 14.8% if <10mm, and 23.9% if <15mm, had a positive Quantiferon Gold In-Tube result. Prior BCG vaccination was associated with a negative interferon gamma release assay result (Quantiferon Gold In-Tube: OR=0.41, p<0.001; T-SPOT.TB: OR=0.41, p<0.001). Young age was a predictor of indeterminate IGRA, but indeterminate rates were low (3.6% in <5years, 1% in >5 years). Conclusions: Our data show BCG vaccination may be effective in protecting children against Mycobacterium tuberculosis infection. To restrict use of interferon-gamma release assays to children with positive skin tests risks underestimating latent infection

Vulvar carcinoma in a 12-year-old girl with vertically acquired human immunodeficiency virus infection

We report the first case of a girl with vertically acquired human immunodeficiency virus (HIV) infection, who developed invasive squamous cell carcinoma of the vulva at 12 years of age. Lesions resembling bowenoid papulosis covered the perianal area as well. She underwent a nonmutilating surgical excision of the infiltrating lesion. More than 3 years later, her clinical condition is excellent, although dysplastic, noninfiltrating multifocal lesions persist. This case highlights the need to perform careful periodic genital examinations in all HIV-infected children and adolescents born to HIV-positive mother

Hospitalization of children born to human immunodeficiency virus-infected women in Europe. The European Collaborative Study

OBJECTIVE: To describe the pattern of inpatient hospital service use in the first 5 years of life of all children born to HIV-infected women in 10 pediatric centers of the European Collaborative Study. BACKGROUND: Little information is available on the need for hospitalization of children born to HIV-infected women, especially those uninfected, despite the fact that they may be at risk of social deprivation and poor health because of family circumstances. METHODS: Data on 1189 children enrolled between 1986 and 1997 and followed prospectively since birth according to a standard protocol were analyzed. RESULTS: This analysis included 151 HIV-infected and 811 uninfected children. One hundred forty (12%) infants had delayed postnatal discharge, mainly for drug withdrawal symptoms and prematurity. Uninfected children had 0.5 admission per 5 child years compared with 2.4 for infected children. From life table analysis, an estimated 48% of infected and 17% of uninfected children will have been admitted by age 12 months. Nearly 60% (3304 of 5604) of the total inpatient days of infected children occurred after AIDS diagnosis. Infected children were 4 times more likely to be hospitalized than uninfected children of the same age, and children with symptomatic mothers were 13 times more likely to be admitted for a nonmedical reason. CONCLUSIONS: Whereas hospitalization of infected children poses an expected burden on the health care system, the use of such services by uninfected children is largely explained by their social background and provides an argument for better support for families affected by HI

Vertical transmission of HIV-1: maternal immune status and obstetric factors. The European Collaborative Study.

OBJECTIVE: To estimate the effect of maternal factors and events around the time of delivery on HIV-1 vertical transmission risk. DESIGN: Prospective study. SETTING: Twenty-two obstetric and paediatric clinics in seven European countries. PATIENTS OR OTHER PARTICIPANTS: Mothers identified as HIV-infected before or at delivery and their children. MAIN OUTCOME MEASURE: Paediatric HIV infection. RESULTS: By November 1995, 1846 mothers with 1945 children had been enrolled. The vertical transmission rate was 16.4% (95% confidence interval, 14.5-18.3). Parity, maternal age, race, mode of HIV acquisition, injecting drug use and sex of infant were not statistically significantly associated with risk of transmission. Children delivered vaginally were more likely to be infected than those delivered by Caesarean section. However, in vaginal deliveries the procedures used, duration of ruptured membranes or length of second-stage labour were not related to transmission. Transmission increased almost linearly with decreasing CD4 cell count, but there was no such trend for CD8 cell count. Women with CD4 cell counts below 200 x 10(6)/l were significantly more likely to deliver early (chi 2 for trend, 14.02; P < 0.001). Very premature infants were at increased risk of infection, but after about 35 weeks gestation the transmission rate remained stable, with no increase in late pregnancy. This trend was confirmed after allowing for maternal CD4 cell count. CONCLUSIONS: The rate of vertical transmission increases linearly with decreasing maternal CD4 cell count. Women with fewer than 200 x 10(6) CD4 cells/l have an increased risk of premature delivery, which would affect timing of interventions. The stable transmission rate after 35 weeks gestation suggests little acquisition of infection during late pregnanc

Prolonged zidovudine administration induces a moderate increase in the growth and steroidogenic capacity of the rat adrenal cortex

Zidovudine (AZT) is an antiretroviral drug widely used in the treatment of human immunodeficiency virus (HIV)-infected patients, whose prolonged administration was found to cause toxic lesions in cardiomyocytes in humans and experimental animals. Alterations in adrenocortical secretion were frequently observed in HIV patients, but it is not clear whether medication is involved in the production of these complications. Hence, we studied in vivo and in vitro, the effects of AZT on the rat adrenal cortex. The prolonged AZT administration (100 mg/kg per day for 4 months) did not cause overt qualitative morphological alterations of adrenocortical cells, which, however, underwent a net hypertrophy. Hypertrophy is associated with increases in the volume and surface area per cell of the mitochondrial compartment and smooth endoplasmic reticulum (where the enzymes of steroid synthesis are located), and a marked decrease in the volume of the lipid-droplet compartment (where cholesterol and its esters, the precursors of steroid hormones, are stored). AZT chronic treatment induced rises in the plasma concentrations of aldosterone and corticosterone, and in the basal and ACTH-stimulated in vitro secretion of these hormones from adrenal slices. The 24-h exposure to AZT (10(-5) M) did not significantly affect either secretory activity or proliferation and apoptotic rates of cultured rat adrenocortical cells. Taken together, these findings suggest that AZT chronic treatment enhances the growth and steroidogenic capacity of rat adrenal cortex, probably by activating the central branch of the hypothalamic-pituitary-adrenal axis. The toxic activity of AZT is thought to depend on increased production of ROS. On these grounds, it is likely that the lack of toxic effect of AZT on adrenocortical cells is due to their very elevated content in vitamin C, which prevents the deleterious effect of the AZT-induced increase in intracellular ROS production

HIV-infected pregnant women and vertical transmission in Europe since 1986

Prospective study. Methods: Analysis of prospective data on 2876 pregnant HIV-infected women and their 3076 infants. Factors examined included maternal socio-demographic, immunological and virological characteristics, antiretroviral therapy and pregnancy outcome. Results: Among women enrolled, the proportion with heterosexual acquisition of infection has increased significantly from 59% (201/342) in 1985-1987 to 69% (327/ 471) after 1997 while the proportion acquiring HIV through injecting drug use has declined. Overall median CD4 cell count was 440 x 10(6)/l and 41% of women had undetectable viral load at delivery. In 1995 28% (72/256) of mother-child pairs received the full 076 regimen to reduce risk of vertical transmission, rising significantly to 89% (116/130) by 1999. Use of triple therapy started in pregnancy has increased significantly from (1% 1/153) in 1997 to 44% (47/107) in 1999. Exposure to antiretroviral therapy was not associated with prevalence or pattern of congenital abnormalities (P = 0.88) but was associated with reversible anaemia in the infant (P<0.002). The elective cesarean section rate has increased from 10% in 1992 to 71% in 1999/2000. The vertical transmission rate declined from 15.5% by 1994 to 2.6% after 1998. In multivariate analysis, adjusting for maternal CD4 cell count, risk of vertical transmission was reduced by 66% (95% confidence interval, 37-82%) with the full 076 regimen and by 60% (95% confidence interval, 33-73%) with elective cesarean section delivery. Conclusions: Changes in treatment of adult HIV disease have affected the management of infected pregnant women. Despite therapeutic and surgical interventions, vertical transmission still occurs

Clinical Features and Follow-Up in Patients with 22q11.2 Deletion Syndrome

Objective To investigate the clinical manifestations at diagnosis and during follow-up in patients with 22q11.2 deletion syndrome to better define the natural history of the disease. Study design A retrospective and prospective multicenter study was conducted with 228 patients in the context of the Italian Network for Primary Immunodeficiencies. Clinical diagnosis was confirmed by cytogenetic or molecular analysis. Results The cohort consisted of 112 males and 116 females; median age at diagnosis was 4 months (range 0 to 36 years 10 months). The diagnosis was made before 2 years of age in 71% of patients, predominantly related to the presence of heart anomalies and neonatal hypocalcemia. In patients diagnosed after 2 years of age, clinical features such as speech and language impairment, developmental delay, minor cardiac defects, recurrent infections, and facial features were the main elements leading to diagnosis. During follow-up (available for 172 patients), the frequency of autoimmune manifestations (P =.015) and speech disorders (P =.002) increased. After a median follow-up of 43 months, the survival probability was 0.92 at 15 years from diagnosis. Conclusions Our data show a delay in the diagnosis of 22q11.2 deletion syndrome with noncardiac symptoms. This study provides guidelines for pediatricians and specialists for early identification of cases that can be confirmed by genetic testing, which would permit the provision of appropriate clinical management