Catherine M. Wilfert

Perinatal Transmission of Human Immunodeficiency Virus Type 1 by Pregnant Women with RNA Virus Loads <1000 Copies/mL

In a collaboration of 7 European and United States prospective studies, 44 cases of vertical human immunodeficiency virus type 1 (HIV-1) transmission were identified among 1202 women with RNA virus loads <1000 copies/mL at delivery or at the measurement closest to delivery. For mothers receiving antiretroviral treatment during pregnancy or at the time of delivery (or both), there was a 1.0% transmission rate (8 of 834; 95% confidence interval [CI], 0.4%-1.9%), compared with 9.8% (36 of 368; 95% CI, 7.0%-13.4%) for untreated mothers (risk ratio, 0.10; 95% CI, 0.05-0.21). In multivariate analysis adjusting for study, transmission was lower with antiretroviral treatment (odds ratio [OR], 0.10; P<.001), cesarean section (OR, 0.30; P=.022), greater birth weight (P=.003), and higher CD4 cell count (P=.039). In 12 of 44 cases, multiple RNA measurements were obtained during pregnancy or at the time of delivery or within 4 months after giving birth; in 10 of the 12 cases, the geometric mean virus load was >500 copies/mL. Perinatal HIV-1 transmission occurs in only 1% of treated women with RNA virus loads <1000 copies/mL and may be almost eliminated with antiretroviral prophylaxis accompanied by suppression of maternal viremia.

Disclosure of illness status to children and adolescents with HIV infection

Many children with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome are surviving to middle childhood and adolescence. Studies suggest that children who know their HIV status have higher self-esteem than children who are unaware of their status. Parents who have disclosed the status to their children experience less depression than those who do not. This statement addresses our current knowledge and recommendations for disclosure of HIV infection status to children and adolescents.

A Multicenter Trial of Oral Zidovudine in Children with Advanced Human Immunodeficiency Virus Disease

BACKGROUND AND METHODS Zidovudine has been shown to be an effective antiretroviral treatment in adults with human immunodeficiency virus (HIV) infection. We examined the safety of zidovudine and the tolerance of and therapeutic response to the drug in 88 children with advanced HIV disease. During a 24-week outpatient trial, zidovudine (180 mg per square meter of body-surface area per dose) was given by mouth every six hours and serial measurements were made of clinical, immunologic, and virologic indexes. Children who completed 24 weeks of treatment were permitted to continue receiving zidovudine. RESULTS Of the 88 children (mean age, 3.9 years; range, 4 months to 11 years), 61 completed the initial 24-week trial, and 49 continued to receive zidovudine for up to 90 weeks (median follow-up, 56 weeks). The patients generally tolerated zidovudine well. One or more episodes of hematologic toxicity occurred in 54 children (61 percent)--anemia (hemoglobin level, less than 75 g per liter) in 23 children (26 percent) and neutropenia (neutrophil count, less than 0.75 x 10(9) per liter) in 42 (48 percent). Many of these abnormalities resolved spontaneously, but 30 children required transfusions or a modification of the dose of zidovudine. Only three children had to stop receiving the drug because of hematologic toxicity. Kaplan-Meier analysis demonstrated that the probability of survival was 0.89 after 24 weeks and 0.79 after 52 weeks. There was marked improvement in weight gain, cognitive function (mainly in children less than 3 years old), serum and cerebrospinal fluid concentrations of p24 antigen, and the proportion of cerebrospinal fluid cultures negative for HIV. CD4+ lymphocyte counts (mean at base line, 0.263 x 10(9) per liter) improved during the first 12 weeks, although the improvement was not sustained through the 24th week. CONCLUSIONS Zidovudine in a dose of 180 mg per square meter every six hours can be safely administered to children with advanced HIV disease. The resultant clinical, immunologic, and virologic improvements in children are similar to those reported with zidovudine in adults.

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.

Role of Clinical Microbiology Laboratories in the Management and Control of Infectious Diseases and the Delivery of Health Care

Modern medicine has led to dramatic changes in infectious diseases practice. Vaccination and antibiotic therapy have benefited millions of persons. However, constrained resources now threaten our ability to adequately manage threats of infectious diseases by placing clinical microbiology services and expertise distant from the patient and their infectious diseases physician. Continuing in such a direction threatens quality of laboratory results, timeliness of diagnosis, appropriateness of treatment, effective communication, reduction of health care-associated infections, advances in infectious diseases practice, and training of future practitioners. Microbiology laboratories are the first lines of defense for detection of new antibiotic resistance, outbreaks of foodborne infection, and a possible bioterrorism event. Maintaining high-quality clinical microbiology laboratories on the site of the institution that they serve is the current best approach for managing todays problems of emerging infectious diseases and antimicrobial agent resistance by providing good patient care outcomes that actually save money.

Integrating prevention of mother-to-child HIV transmission into routine antenatal care: the key to program expansion in Cameroon.

With funds from Elizabeth Glaser Pediatric AIDS Foundation, the Cameroon Baptist Convention Health Board implemented a program to prevent mother-to-child transmission of HIV-1 (PMTCT) as part of its routine antenatal care, with single-dose maternal and infant peripartum nevirapine (NVP) prophylaxis of HIV-positive mothers and their babies. Nurses, midwives, nurse aides, and trained birth attendants counseled pregnant women, obtained risk factor data, and offered free HIV testing with same-day results. From February 2000 through December 2004, this program rapidly expanded to 115 facilities in 6 of Cameroons 10 provinces, not only to large hospitals but to remote health centers staffed by trained birth attendants. We trained 690 health workers in PMTCT and counseled 68,635 women, 91.9% of whom accepted HIV testing. Of 63,094 women tested, 8.7% were HIV-1-positive. Independent risk factors for HIV-1 infection included young age at first sexual intercourse, multiple sex partners, and positive syphilis serology (P < 0.001 for each). We counseled 98.7% of positive and negative mothers on a posttest basis. Of 5550 HIV-positive mothers, we counseled 5433 (97.9%) on single-dose NVP prophylaxis. Consistent training and programmatic support contributed to rapid upscaling and high uptake and counseling rates.

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.

Over five-year follow-up of Oka/Merck varicella vaccine recipients in 465 infants and adolescents.

A total of 465 healthy infants and adolescents ages 12 months to 17 years without a known history of varicella or recent exposure to varicella-zoster virus VZV were immunized with live attenuated Oka/Merck varicella vaccine from November, 1984, through April, 1989. The vaccine administered was from 1 of 7 production lots containing from 950 to 3265 plaque-forming units and was well-tolerated with few side effects. The seroconversion rate for seronegative subjects was 94.6% (403 of 426). This varied by lot from 85% (950 plaque-forming units) to 100% (3010 and 3265 plaque-forming units). Breakthrough disease after exposure to varicella in seroconverters during 5 to 10 years of follow-up was 18.6% (75 of 403). The breakthrough disease was characterized by a maculopapular rash with a median of 35 lesions, most of which were macules. Breakthrough disease lasted a median of 5 days and the median temperature was 99°F; 65.3% (49 of 75) of subjects were afebrile and 2.7% (2 of 75) of subjects had temperatures of > 102.9°F. Varicella vaccine provides excellent (94.6%) seroconversion, and most children who developed breakthrough disease (18.6%) experienced a modified, milder form of illness than has been observed with natural varicella in unvaccinated subjects.

Provision of care following prevention of mother-to-child HIV transmission services in resource-limited settings

Objective:To evaluate the provision of care for mother and child after institution of prevention of mother-to-child transmission (PMTCT) of HIV services. Design:As part of an effort to improve services, we undertook a review of our multicountry PMTCT program. Methods:Review of key indicators from our PMTCT database and reporting practices from January 2005 to June 2006 throughout 18 resource-limited countries. Results:1 066 606 pregnant women were counseled and tested, and 102 336 tested HIV-positive. Antiretroviral prophylaxis was dispensed to 81 384 mothers and 52 342 HIV-exposed infants. From available reporting, 1388 pregnant women were dispensed antiretroviral drugs for treatment and 9060 children received cotrimoxazole prophylaxis at 6 weeks. Conclusions:PMTCT services are integrated into maternal-child health services but adult and pediatric care and treatment programs often function independently, without coordination or linkages. Integrating care into maternal-child health services and linking mothers HIV status to child are necessary for HIV-infected mothers and HIV-exposed children to receive appropriate follow-up and treatment.

Growth as a prognostic indicator in children with human immunodeficiency virus infection treated with zidovudine

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.