Impact of protease inhibitor-containing combination antiretroviral therapies on height and weight growth in HIV-infected children.

OBJECTIVE: To examine beneficial or detrimental effects of protease inhibitor (PI)-containing antiretroviral regimens on height and weight growth in children with human immunodeficiency virus (HIV) infection. METHODS: A prospective cohort study was conducted of 906 HIV-infected children, from pediatric research clinics in the United States, who were between 3 months and 18 years of age and who had height and weight assessed in 1995 (before introduction of PIs in this population) and at least once more through 1999. Changes in age- and gender-adjusted height and weight growth associated with PI use were assessed. RESULTS: Compared with a healthy reference population, children were more affected in height (mean z score: -0.90 [18th percentile]) than in weight (mean z score: -0.42 [34th percentile]) at baseline (1995). Two thirds of children received at least 1 PI during 1996 to 1999. In the multivariate mixed effects regression models adjusted for baseline log(10) CD4 cell count, baseline age, gender, and race/ethnicity, the use of PIs was associated with per-year gains of 0.13 z scores in height and 0.05 z scores in weight relative to the expected growth with non-PI-containing regimens (eg, after 1 year of PI use, a representative 6-year-old boy in our study would be approximately 0.7 cm taller and 0.1 kg heavier than if he had not received PIs). No significant differential effects of PIs on height or weight growth according to specific agents or children's sociodemographic or clinical characteristics were found. CONCLUSIONS: Although the use of PI-containing regimens was not associated with growth retardation, it was associated with only small annual increments in height and weight growth in HIV-infected children.

Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1.

BACKGROUND: Combination therapy including protease inhibitors has been shown to be effective in treating adults infected with human immunodeficiency virus type 1 (HIV-1), but there are only limited data regarding the treatment of children and adolescents. METHODS: A cohort of 1028 HIV-1-infected children and adolescents, from birth through 20 years of age, who were enrolled in research clinics in the United States before 1996 was followed prospectively through 1999. We used proportional-hazards regression models to estimate the effect on mortality of combination therapy including protease inhibitors. RESULTS: Seven percent of the subjects were receiving combination therapy including protease inhibitors in 1996; by 1999, 73 percent were receiving such therapy. In univariate analyses, a higher base-line percentage of lymphocytes that were CD4-positive, a higher weight for age, a higher height for age, black race, Hispanic ethnic background, younger age, and perinatally acquired infection were associated with a longer median time to the initiation of this type of therapy (P<0.001). After adjustment for covariates, the differences among racial and ethnic groups in the time to initiation were not statistically significant. Mortality declined from 5.3 percent in 1996 to 2.1 percent in 1997, 0.9 percent in 1998, and 0.7 percent in 1999 (P for trend <0.001). There were reductions in mortality in all subgroups defined according to age, sex, percentage of CD4+ lymphocytes, educational level of the parent or guardian, and race or ethnic background. In adjusted analyses, the initiation of combination therapy including protease inhibitors was independently associated with reduced mortality (hazard ratio for death, 0.33; 95 percent confidence interval, 0.19 to 0.58; P<0.001). CONCLUSIONS: The use of combination therapy including protease inhibitors has markedly reduced mortality among children and adolescents infected with HIV-1.

Status of selected nutrients and progression of human immunodeficiency virus type 1 infection.

BACKGROUND: Immune function is highly dependent on nutritional status because the large mass and high rate of cellular turnover of the immune system make it a major user of nutrients. Furthermore, nutrient requirements may be increased during acute and chronic infections, including HIV-1 infection. OBJECTIVE: The current study was designed to assess relations among HIV-1 progression and 11 nutritional and demographic variables. DESIGN: The participants were 106 HIV-infected outpatients and 29 uninfected control subjects (n = 89 men and 46 women; age range: 35-57 y). The HIV-infected subjects represented a broad range of disease progression. RESULTS: We found lower concentrations of plasma and erythrocyte magnesium and of erythrocyte reduced glutathione beginning early in the course of HIV-1 infection. Significantly decreased hematocrit and increased serum copper concentration developed only late in the course of the disease. Statistically significant univariate associations were found between the CD4(+) T lymphocyte count and hematocrit, plasma magnesium concentration, and plasma zinc concentration. The lowest erythrocyte magnesium concentrations occurred in HIV-infected subjects who consumed alcoholic beverages. Independent variables that were significant joint predictors of CD4(+) cell count in multiple regression analyses were hematocrit and plasma free choline and zinc concentrations. These 3 factors together explained 43% of the variability in CD4(+) cell counts. CONCLUSION: The results provide evidence that compromised nutritional and antioxidant status begin early in the course of HIV-1 infection and may contribute to disease progression.

Continuum of palliative care: lessons from caring for children infected with HIV-1.

PIP: This article presents the essence of continuum of palliative and hospice care for HIV-infected children. Based on the principles of palliative care and the provision of hospice services, the relief of suffering has not always been available to most children with life-limiting illnesses. The palliative care ensures child's comfort and maximum function through the course of their illness. The guiding ethical principle of palliative care includes autonomy, beneficence, non-malfeasance, and justice. Thus, the family and child are full partners with the health care team in management decisions. Its benefit did not just be reserved for end-of-life care. It starts from the time an HIV-1 infected woman becomes pregnant through the course of disease and eventual death of her child. However, there were barriers in providing palliative care. One of which was the lack of appreciation towards acute and chronic pain associated with disease and painful procedures. Another thing was the social and economic barriers to the provisions of appropriate palliative care and hospital services, which also exist. A collaborative multidiscipline program will therefore provide the best environment in providing palliative and hospice care. To sum up, a child with life-limiting illnesses should receive palliative care and hospice services that give them the best quality of life and ease the burden of dying.^ieng

Lack of tumors in infants with perinatal HIV-1 exposure and fetal/neonatal exposure to zidovudine.

Zidovudine (ZDV) therapy during pregnancy and to the neonate reduced perinatal HIV transmission by nearly 70% in Pediatric AIDS Clinical Trials Group (PACTG) protocol 076. ZDV has been reported as positive in several in vitro carcinogenicity screening tests. We evaluated the short-term risk for tumors in 727 children with known ZDV exposure enrolled into the PACTG 076/219 and the Women and Infants Transmission Study (WITS). ZDV exposure in utero (antepartum) occurred in 97% and 99% of infants in PACTG 076/219 or WITS, respectively. Mean follow-up was 38.3 months with 366.9 person years follow-up for PACTG 076/219 and 14.5 months with 743.7 person years follow-up for WITS. No tumors of any nature were observed; relative risk was 0 (95% confidence interval [CI], 0-17.6). These data are reassuring regarding the short-term lack of tumors for ZDV-exposed infants observed to date. Longitudinal, standardized follow-up for infants with in utero antiretroviral exposure is necessary to assess long-term carcinogenicity.

When a child with a chronic condition needs hospitalization.

The hospitalization of a chronically ill child requires meticulous orchestration. Treatment recommendations must be transmitted to the family in a coherent and supportive fashion. Patient comfort and nutrition must be maintained, and psychological support provided. Discharge planning is often extensive. To promote continuity of care, appointment of a case manager is recommended.

Lead poisoning--one approach to a problem that won't go away.

A reduction in sources of environmental lead exposure has resulted in substantial declines in mean blood lead concentrations of all age groups in the United States. However, some segments of the population continue to have unacceptable levels of lead exposure and elevated blood lead concentrations. In addition, virtually all residents of industrialized countries have bone lead stores that are several orders of magnitude greater than those of our preindustrial ancestors. Recent studies suggest that these skeletal lead stores adversely affect health and can contribute to reduced birth weights, aggressive behavior in children, and anemia, hypertension, and kidney disease in adults. Evidence is described that demonstrates that an increase in dietary calcium consumption can reduce lead absorption and toxicity from exogenous and endogenous lead exposure. A relatively inexpensive and effective way to reduce the substantial morbidity that will result from widespread lead exposure is by fortification of a variety of foods with low levels of calcium. This approach can complement other efforts to prevent lead exposure and reduce lead toxicity.

Historical perspectives on the evolution in understanding the importance of nutritional care in pediatric HIV infection.

Women, perinatally-infected infants, and sexually exposed and exploited youths and adolescents have become a major focus of the worldwide HIV/AIDS pandemic. Increased perinatal screening, improvement in early infant diagnosis, and the benefits of primary HIV therapies have increased the numbers identified and longevity of infants and children living with HIV. This increase in survival is associated with HIV/AIDS becoming a chronic multiorgan system disease that requires a multidiscipline comprehensive care approach. The combination of poor oral intake, increased loss, and increased metabolic needs of long-term surviving HIV-infected children are obstacles to both survival and quality of life. HIV-infected children and their families need supportive care services including nutritional as well as primary therapy. Clinical guidelines for effective nutrition interventions must be developed to prevent and treat failure to thrive and wasting syndrome. Gains in survival duration must be linked to enhanced quality of life through supportive care, including comprehensive nutritional services that have their efficacy documented by appropriate clinical trials.

Older children and adolescents living with perinatally acquired human immunodeficiency virus infection.

OBJECTIVE: To describe the clinical, immunologic, and psychosocial characteristics of children living with perinatally-acquired human immunodeficiency virus (HIV) infection beyond the age of 9 years. METHODS: This is a descriptive cohort study of 42 surviving perinatally infected children older than 9 years followed at the Children's Hospital Acquired Immunodeficiency Syndrome (AIDS) Program (part of a university-based inner city medical center) as of June 1993. The study is based on medical record data of clinical, immunologic, and psychosocial parameters. RESULTS: The cohort includes 20 boys and 22 girls with a mean age of 136 months. The mean age at diagnosis of HIV infection was 88 months, and 59.5% were asymptomatic at the time of diagnosis. Currently, after a mean follow-up period of 48 months from diagnosis, 23.8% remain asymptomatic, 19.1% have non-AIDS-defining HIV-related symptoms, and 57.1% have AIDS; 85.7% of the cohort did not develop HIV-related symptoms until after 48 months of age (late-onset prolonged survivors). There was an average annual decline of 71.4 CD4+ cells/microL in the cohort from the ages of 7 to 16 years, and 21.4% have a current CD4+ lymphocyte count of greater than 500 cells/microL, 28.6% between 200 and 500 cells/microL, and 50% less than 200 cells/microL; 76% are orphaned as a result of maternal death, with the majority of the cohort (60%) cared for by extended family members. Disclosure of diagnosis has occurred in 57.1%. The vast majority of the cohort (76%) are attending regular school, with the remainder in special education. CONCLUSIONS: Although close to one quarter of the children and adolescents ages 9 to 16 years living with perinatally acquired HIV infection described in this cohort remain asymptomatic and have a relatively intact immune system, the remainder are living with significant HIV-related symptoms, many of which are chronic in nature and have an impact on daily living. The children in this cohort had both significant immunologic deterioration and symptomatic disease progression during the mean follow-up period of 48 months from the time of diagnosis with HIV infection.

Determination of CD4 and CD8 lymphocyte subsets by a new alternative fluorescence immunoassay.

The purpose of this study was to evaluate a new alternative fluorescence immunoassay method (Zymmune CD4/CD8 Cell Monitoring Kit; Zynaxis, Inc., Malvern, Pa.) for determining the absolute CD4+ and CD8+ T-lymphocyte concentrations in whole blood. The investigation was performed as a two-site comparison of the reference whole blood flow cytometric method with the Zymmune method. In this investigation, a total of 166 patient samples were evaluated of which approximately 20% were from human immunodeficiency virus-positive individuals. The mean value for samples performed by the Zymmune CD4 assay was 1,094 (range, 74 to 2,586) cells per microliters, while the reference method yielded a mean of 890 (range, 35 to 2,033) cells per microliter. The correlation coefficient for regression analysis was 0.940. The mean value for samples performed by the Zymmune CD8 assay was 700 (range, 212 to 1,813) cells per microliter, while the reference method yielded a mean of 546 (range, 82 to 2,158) cells per microliter. The correlation coefficient for regression analysis was 0.921. No site-specific differences or trends in CD4 or CD8 values were seen when the data were analyzed by site of collection. The average precision of the CD4 assay varied from 6 to 14%, corresponding to the high and low concentration ranges. For CD8, the average precision varied from 8.3 to 16% over the respective high to low concentration ranges. We conclude that the Zymmune CD4/CD8 Cell Monitoring Kit method provides absolute CD4+ and CD8+ T-lymphocyte concentrations which are equivalent to those given by the reference flow cytometric method.

Viral measurement by polymerase chain reaction-based assays in human immunodeficiency virus-infected infants.

Serial samples from human immunodeficiency virus-infected infants in the first year of life were analyzed by quantitative human immunodeficiency virus polymerase chain reaction assays. Very high, persistent levels of plasma RNA and proviral DNA were detected throughout the study period, suggesting the absence of an effective immune response. Most patients had normal CD4 lymphocyte counts and were symptom free for the first 3 to 6 months despite high levels of viral replication. These findings support the evaluation of early intervention (before symptoms develop) and efforts to establish the predictive value of these assays.

The many needs of the HIV-infected child.

25% to 35% of infants exposed to maternal HIV during the perinatal period become infected. The virus is now the fifth leading cause of death in children under 15 years. Until recently, most infected children were symptomatic by age two and died by age six, but today many survive into their teens. The medical, physical, and psychosocial needs of these long-term survivors are discussed.