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Biomedical subjects

C Wilfert

Publications and source records attributed to C Wilfert.

At least 19 recordsLinked to original sources
PubMed2000

Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children < or = 5 years of age, Pediatric Spectrum of HIV Disease project (PSD), USA.

BACKGROUND: In response to recent reports of mitochondrial dysfunction in HIV-uninfected infants exposed to antiretroviral (ARV) prophylaxis, the Perinatal Safety Review Working Group reviewed deaths in five large HIV-exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort. METHODS: Hospitalization, clinic and death records for deceased HIV-uninfected and HIV-indeterminate children who were less than 5 years of age were reviewed. Standard definitions were used to classify HIV infection status and the likelihood that signs and symptoms were related to mitochondrial dysfunction. Children were classified as having signs and symptoms that were considered (1) unrelated, (2) unlikely, (3) consistent with, or (4) likely related to mitochondrial disease. SIDS deaths were put into a separate category. RESULTS: 8,465 of 13,125 HIV-exposed children were either HIV-uninfected or HIV-indeterminate. Among the 84 deaths in the subgroup of 8,465 children, 9 were considered in Class 2 (unlikely), 4 were considered in Class 3 (consistent with), and none were considered in Class 4 (likely). 97% of those children who received ARV prophylaxis received zidovudine alone. None of the HIV-uninfected deaths were classified in 2, 3, or 4; and only one of these was exposed to ARV prophylaxis. Among the 3 HIV-indeterminate children who were classified in 3 (consistent with), 2 had no or unknown ARV exposure before 1994 when use of ZDV prophylaxis became the standard of care. Both HIV-uninfected and HIV-indeterminate children with ARV exposure or unknown exposure had lower mortality rates than children without ARV exposure. CONCLUSION: Monoprophylaxis with ZDV was not associated with higher death rates in the cohort of 8,465 children or with any findings likely consistent with mitochondrial dysfunction among the 85 deaths. Ongoing monitoring of drug safety in large multi-site prospective cohort studies of HIV-exposed children is essential in the era of highly active antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Trends in human immunodeficiency virus (HIV) counseling, testing, and antiretroviral treatment of HIV-infected women and perinatal transmission in North Carolina.

Since 1993, trends in perinatal human immunodeficiency virus (HIV) transmission have been monitored by use of chart review of patients identified at a central diagnostic laboratory. In the population studied, either pre- or postnatal antiretroviral therapy to the infant increased from 21% in 1993 to 95% in 1997. Concurrently, the number of HIV-infected infants declined from 25 in 1993 to 4 in 1997. The complete Pediatric AIDS Clinical Trials Group Protocol 076 regimen was the most effective in reducing transmission (3.1%). Twenty-two of 35 infants who became infected in 1995-1997 had mothers who did not receive antiretroviral therapy, although counseling practices improved with time. In 1995, 87% of the mothers of HIV-seropositive infants were counseled, whereas in 1997, 96% were counseled (P<.005). None of 59 infants tested had high-level phenotypic zidovudine resistance, although 5 (8.8%) of 57 infants had virus isolates with at least one mutation in the reverse transcriptase gene associated with reduced phenotypic susceptibility to zidovudine.

Anti-HIV Agents↗
PubMed1999

Planning for children whose parents are dying of HIV/AIDS. American Academy of Pediatrics. Committee on Pediatric AIDS, 1998-1999.

Although the character of acquired immunodeficiency syndrome is changing into a chronic illness, it is estimated that by the end of this century, 80 000 children and adolescents in the United States will be orphaned by parental death caused by human immunodeficiency virus infection. Plans for these children need to be made to ensure not only a stable, consistent environment that provides love and nurturing, but also the medical and social interventions necessary to cope with the tragic loss. Pediatricians should become aware of local laws and community resources and initiate discussion early in the course of parental illness to facilitate planning for the future care and custody of the children. States need to adopt laws and regulations that provide flexible approaches to guardianship and placement of children orphaned by acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Perinatal HIV infection and the effect of zidovudine therapy on transmission in rural and urban counties.

OBJECTIVES: To assess health care providers' identification of human immunodeficiency virus (HIV)-exposed infants, to ascertain the prevalence of transplacental or oral zidovudine treatment among infants exposed to HIV, and to estimate the impact of zidovudine use on perinatal transmission in rural and urban North Carolina. DESIGN: Survey of North Carolina newborns tested for HIV infection in 1993 and 1994 compared with the number of anonymous HIV-positive childbearing women. SETTING: North Carolina hospitals, public health clinics, and private physicians' offices. MAIN OUTCOME MEASURES: Rates of identification of HIV-exposed infants and of perinatal HIV-1 transmission, determined by HIV culture and polymerase chain reaction testing in the infants. RESULTS: The proportion of HIV-exposed children in North Carolina who were identified and tested increased from 60% in 1993 to 82% for all of 1994, and to more than 90% for the last quarter of 1994. The HIV-exposed infants born in rural counties were more likely to be recognized than those born in urban counties (P<.001). In 1994, most infants were evaluated relatively early in life: 39% by 1 week of age, 63% by 6 weeks, and 76% by 3 months. Among infants with recognized HIV exposure, transmission decreased significantly between 1993 and 1994, from 21% to 8.5%, respectively (P=.009). After the announcement of the results of the AIDS Clinical Trials Group Protocol 076, zidovudine was given to 75% of HIV-positive women who delivered infants in North Carolina. Only 5.7% of infants who received any zidovudine became infected, compared with 18.9% of infants who received no zidovudine (P=.007). CONCLUSIONS: Health care providers in North Carolina are identifying most of the state's HIV-seropositive pregnant women, treating them with zidovudine, and testing their infants soon after birth for HIV infection. The use of zidovudine in pregnant women and their infants has reduced perinatal HIV transmission in the state.

AIDS Serodiagnosis↗
PubMed1994

Growth as a prognostic indicator in children with human immunodeficiency virus infection treated with zidovudine. AIDS Clinical Trials Group Protocol 043 Study Group.

OBJECTIVE: To assess measures of growth as prognostic indicators in response to zidovudine treatment in children with symptomatic human immunodeficiency virus infection. METHODS: We retrospectively assessed data from AIDS Clinical Trials Group Protocol 043, an open-label, phase II study of oral zidovudine therapy (180 mg/m2 per dose every 6 hours) in children with human immunodeficiency virus who have severe symptoms. Several variables were evaluated for their prognostic significance: CD4+ lymphocyte percentage; rates of weight gain and linear growth; entry weight, height, and weight-for-height z scores for age; race; gender; age; and route of transmission. RESULTS: The overall survival rate as of April 1, 1992 (4 years after study initiation), was 44%, with a median survival of 37.9 months. The risk of death was greatest in children with CD4+ lymphocyte percentages < 20% (relative risk, 3.49), but was also increased in children who had a weight-for-age z score < -2 on entry to the study (relative risk, 1.53) and in those who failed to gain weight at the 25th percentile rate or greater during the first 6 months of therapy (relative risk, 2.03). These three factors, as well as race and gender, were found to be significant predictors in a multivariate, proportional-hazards model of survival. Entry height-for-age and height growth rates did not have predictive value for survival in univariate or multivariate analyses. CONCLUSIONS: Weight-for-age and rate of weight gain are important, easily obtained, and inexpensive prognostic indicators in children with symptomatic human immunodeficiency virus treated with zidovudine. Both were less predictive of survival than the entry CD4+ lymphocyte percentage.

Adolescent↗
PubMed1993

Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus.

This study evaluated the safety, tolerability, and pharmacokinetics of zidovudine administered intravenously and orally to infants born to women infected with the human immunodeficiency virus. Thirty-two symptom-free infants were enrolled before 3 months of age. The pharmacokinetics of zidovudine were evaluated in each infant after single intravenously and orally administered doses of zidovudine on consecutive days, and during long-term oral administration of the drug for 4 to 6 weeks. As new patients were enrolled, doses of zidovudine were progressively increased from 2 to 4 mg/kg. Therapy was continued for up to 12 months in 7 of the infants proved to be infected with human immunodeficiency virus. Zidovudine was generally well tolerated; 20 children (62.5%) had anemia (hemoglobin level < 10.0 gm/dl) during therapy and 9 (28.1%) had neutropenia (neutrophil count < or = 750 cells/mm3); these hematologic abnormalities usually resolved spontaneously. The total body clearance of zidovudine increased significantly with age, from an average of 10.9 ml/min per kilogram in infants < or = 14 days of age to 19.0 ml/min per kilogram in older infants (p < 0.0001). Concurrently, there was a significant decrease in serum half-life from 3.12 hours in infants < or = 14 days to 1.87 hours in older infants (p = 0.0002). Oral absorption was satisfactory and bioavailability decreased significantly with age, from 89% in infants < or = 14 days to 61% in those > 14 days of age (p = 0.0002). Plasma concentrations of zidovudine were calculated to be in excess of 1 mumol/L (0.267 micrograms/ml) for 4.12 +/- 1.86 hours and 2.25 +/- 0.78 hours after oral doses of 2 mg/kg in infants younger than 2 weeks and 3 mg/kg in older infants, respectively. We conclude that zidovudine administered at oral doses of 2 mg/kg every 6 hours to infants aged less than 2 weeks and 3 mg/kg every 6 hours to infants older than 2 weeks resulted in plasma concentrations that are considered virustatic against human immunodeficiency virus. Zidovudine was well tolerated by infants at these doses.

Administration, Oral↗
PubMed1989

Pharmacokinetics of zidovudine administered intravenously and orally in children with human immunodeficiency virus infection.

Zidovudine pharmacokinetics were determined in 16 children with human immunodeficiency virus infection who were being treated intravenously and orally on an intermittent schedule (every 6 hours). The intravenous doses studied were 80 (n = 3), 120 (n = 4), and 160 (n = 5) mg/m2/dose, infused over 1 hour. Fourteen patients were monitored after an oral dose of zidovudine at 120 (n = 2), 180 (n = 7), or 240 (n = 5) mg/m2/dose. Zidovudine was assayed with a reverse-phase high-pressure liquid chromatography method. Zidovudine disappearance after intravenous administration was rapid and biexponential, with half-lives of 14 and 90 minutes and a total clearance of 641 +/- 161 ml/min/m2. The volume of distribution at steady state was 45 +/- 28 L/m2. These pharmacokinetics parameters are very similar to those reported in adults. When administered orally, zidovudine was rapidly absorbed. The fraction of the oral dose that was bioavailable was 0.68 +/- 0.25, so that a 50% increment in the dose, in the conversion from intravenous to oral administration, resulted in plasma zidovudine concentrations after oral dosing that were nearly identical to those achieved with the 1-hour intravenous infusion. However, a dose of 180 mg/m2 given orally every 6 hours maintained plasma zidovudine concentrations in the target range of 1 mumol/L for less than half of the dosing interval. Other schedules, routes of administration, or oral drug formulations may have to be considered if sustained continuous exposure to micromolar zidovudine concentrations is desired.

Acquired Immunodeficiency Syndrome↗
PubMed1988

The poliovirus sensitivity (PVS) gene is on chromosome 19q12----q13.2.

Sensitivity to nonmodified poliovirus infection is an autosomal dominant trait, specific to primates. The gene for poliovirus sensitivity (PVS) is encoded on human chromosome 19. In order to sublocalize the PVS gene, we infected rodent-human hybrid cell lines that divide human chromosome 19 into four regions with poliovirus 1 and/or 3. When infected, these hybrid cell lines showed the typical cytopathic effect of poliovirus infection only if they contained 19q12----q13.2 as the smallest region of overlap. Appropriate negative and positive controls were used. PVS may be of relevance to myotonic dystrophy (DM) and the inherited motor neuron diseases: to DM because it localizes to the same region of chromosome 19 and to the inherited motor neuron diseases because it encodes a cell-surface receptor expressed on motor neurons.

Cell Line↗