PEDIATRICS Vol. 117 No. 2 February 2006, pp. 273-283 (doi:10.1542/peds.2005-0323)
Quality of Life for Children and Adolescents: Impact of HIV Infection and Antiretroviral Treatment
a Center for Child Health Care Studies, Department of Ambulatory Care and Prevention, Harvard Pilgrim Health Care and Harvard Medical School, Boston, Massachusetts
b Division of Infectious Diseases, Children's Hospital Boston, Boston, Massachusetts
c Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, Massachusetts
d Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
e Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Newark, New Jersey
| ABSTRACT |
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BACKGROUND. HIV/AIDS mortality rates in the United States are declining; pediatric HIV has become a chronic disease, with quality of life (QoL) outcomes assuming greater importance.
OBJECTIVES. To compare QoL among HIV-infected and uninfected children and to assess the impact of different antiretroviral regimens on QoL among HIV-infected children.
METHODS. Perinatally exposed, HIV-infected (N = 1847) and uninfected (N = 712) children and adolescents were studied. Among infected children, 1283 were available for the antiretroviral regimen analysis. QoL domain scores were assessed for subjects 6 months to 4 years, 5 to 11 years, and 12 to 21 years of age, and the impact of infection status and alternative treatment regimens on QoL domains was evaluated.
RESULTS. HIV infection was associated with significantly worse mean adjusted scores for functional status among children 6 months to 4 years of age and health perceptions, physical resilience, physical functioning, and social/role functioning among those 5 to 11 years of age. However, uninfected children 5 to 11 years of age reported significantly worse psychological functioning. HIV-infected children (511 years of age) and adolescents (1221 years of age) receiving no antiretroviral treatment had worse health perceptions. Adolescents receiving no antiretroviral agents also had worse symptoms. When antiretroviral regimens were compared, adolescents receiving protease inhibitor plus nonnucleoside reverse transcriptase inhibitor-containing therapy had worse symptoms, compared with those receiving protease inhibitor-containing therapy; otherwise, no significant differences were found.
CONCLUSIONS. Generally parents of HIV-infected children 6 months to 4 years and 5 to 11 years of age generally reported lower mean QoL scores than did parents of uninfected children, although worse psychological functioning was reported for uninfected children. HIV-infected adolescents not receiving antiretroviral treatment had worse health perceptions and symptoms. We found no consistent QoL differences among children receiving different antiretroviral regimens.
Key Words: HIV quality of life antiretroviral therapy
Abbreviations: CDCCenters for Disease Control and Prevention NNRTInonnucleoside reverse transcriptase inhibitor NRTInucleoside reverse transcriptase inhibitor PACTGPediatric AIDS Clinical Trials Group PIprotease inhibitor QoLquality of life
HIV infection continues to be a significant cause of disability and death worldwide, with an estimated 2.1 million children living with HIV in 2003.1 However, we have seen dramatic decreases in rates of childhood deaths and morbidity attributable to HIV/AIDS in the United States because of the availability of highly active antiretroviral therapy.2, 3 Because children are now living with HIV as a chronic disease, our next challenge is to optimize the health of these children.
Traditional outcome measures of health among HIV-infected children have focused on surrogate measures such as viral load, CD4+ cell percentage, or hospitalizations to describe disease morbidity.49 However, these measures do not capture fully the multidimensional nature of health and thus may not reflect accurately the health preferences of the children or their families. An alternative health measure used to evaluate outcomes for children and adolescents with chronic health conditions is health-related quality of life (QoL). Health-related QoL measures provide a comprehensive assessment of the physical, psychological, and social functioning of children within the context of their developmental stage.10
For HIV-infected children, QoL assessments may provide a distinct advantage over traditional measures of morbidity. For example, outcome measures focused on CD4+ cell percentage or viral load might provide incomplete information about the overall impact of a particular treatment regimen, especially if adverse events are not considered. In addition, benefits of treatment such as improved behavior and ability to participate in activities might remain undetected when measures such as disease progression are examined. Recently, Storm et al11 reported on a study that examined QoL among HIV-infected children 5 to 18 years of age and compared children receiving protease inhibitor (PI) therapy with those receiving non-PI therapy. Although parents of HIV-infected children reported impairment in several QoL domains overall, the authors found no significant differences in QoL between the PI and non-PI groups. However, the study was limited by a lack of available information regarding several relevant measures, including HIV RNA viral load, exact type and duration of treatment, and level of adherence. In addition, the magnitude of the impact of HIV infection on QoL could not be determined because a comparison group was not available. To provide a recent comprehensive picture of health outcomes associated with pediatric HIV infection, we sought (1) to understand the impact of HIV disease on QoL among children by comparing HIV-infected and uninfected children and (2) to determine the association of different antiretroviral regimens with QoL among HIV-infected children and adolescents, controlling for measured severity of illness.
| METHODS |
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Study Population
The study population for these analyses included children and adolescents 6 months to 21 years of age enrolled in Pediatric AIDS Clinical Trials Group (PACTG) protocol 219C from September 15, 2000, to December 31, 2003. PACTG 219C is an observational, prospective, cohort study designed to assess the long-term outcomes of HIV-infected and -exposed children, including survival, QoL, growth and neurologic development, drug-related toxicity, and disease complications. All infected and uninfected infants born to HIV-infected women at PACTG study sites were considered eligible for enrollment. In addition, children and adolescents who acquired HIV infection postnatally were eligible for enrollment in PACTG 219C. Human subjects review boards at participating sites in the United Status and Puerto Rico approved the research protocol. Our analyses focused on cross-sectional data for children and adolescents with perinatal exposure, with the use of baseline clinical, laboratory, and QoL data at the time of study enrollment.
For the first objective, we included perinatally exposed HIV-infected and -uninfected children and adolescents. We excluded participants who did not complete QoL surveys or who had other missing data, such as demographic information. On the basis of these criteria, 1847 infected and 712 uninfected children were available for analysis (Fig 1).
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To address the second objective of determining differences in QoL according to antiretroviral regimen, we included perinatally HIV-infected children who were receiving one of the following treatment regimens at the time of study entry: no antiretroviral treatment, nucleoside reverse transcriptase inhibitors (NRTIs) alone, or nonnucleoside reverse transcriptase inhibitor (NNRTI)-containing, PI-containing, or PI- plus NNRTI-containing regimens. The latter 3 regimens usually included NRTIs as part of the treatment regimen. All treatment regimens were mutually exclusive. Children who were receiving blinded study medications or other antiretroviral agents, such as nucleotide reverse transcriptase inhibitors, were excluded. Furthermore, we limited this study population to subjects who had been receiving 1 of the 5 regimens described above for
3 months at the time of study entry and who reported good adherence, for better assessment of the impact of each treatment regimen. Adherence to therapy was measured with a questionnaire that asked about the number of expected doses for each medication and the number of doses taken by the respondent in the past 3 days.12 Individuals were considered adherent if primary caregivers reported no missed doses.
Among 1847 infected participants, 1283 children and adolescents (197 children 6 months to 4 years of age, 807 children 511 years of age, and 279 adolescents
12 years of age) met the criteria for inclusion in the analysis regarding the impact of treatment on QoL. Participants were excluded for the following reasons: 85 children (5%) were receiving treatment regimens that included an antiretroviral agent that was blinded or did not fall into 1 of the antiretroviral regimens for this study, 187 children (10%) had been receiving a treatment regimen for <3 months, 225 children (12%) reported nonadherence in the past 3 days, and 67 children (4%) had missing information regarding Centers for Disease Control and Prevention (CDC) classification, CD4+ cell percentage, or viral load.
Study Design
We conducted 2 cross-sectional analyses of the children enrolled in PACTG 219C from September 15, 2000, to December 31, 2003. The first analysis was limited to HIV-infected and uninfected children <12 years of age, because of the absence of uninfected youths
12 years of age enrolled in PACTG 219C. Analyses were stratified according to age (6 months to 4 years or 511 years) because of the different QoL measures and different age distributions of infected/uninfected subjects. The second analysis was also stratified according to age (6 months to 4 years, 511 years, or 1221 years) because of the different QoL measures used for each age group.
Race/ethnicity was categorized as white non-Hispanic, black non-Hispanic, Hispanic, or other, on the basis of caregiver reports. The primary caregiver at the time of enrollment was categorized as a biological parent (mother, father, or both), relative, or other. The highest educational level completed by the primary caregiver was used as an indicator of socioeconomic status. Social/environmental context was assessed as the number of negative life events that occurred in the past 12 months, including parent lost job, family member left home, loss of housing or had to move, loss of entitlement, loss of health insurance, family member hospitalized, family member very sick, change of caretaker, separation of parents, divorce of parents, jail sentence of parent, and death in the family. We calculated a total event score as the sum of the number of negative life events.13
A medical history and physical examination were performed at study enrollment. Children were assigned a CDC clinical classification of N (no signs/symptoms), A (mild signs/symptoms), B (moderate signs/symptoms), or C (severe signs/symptoms).14, 15 Laboratory data, including CD4+ cell percentage and HIV-1 RNA viral load, were also collected at study enrollment. Information on the type of medications at study enrollment and the number of antiretroviral regimens the child received before study entry was available to study investigators. The total number of treatment regimens children had experienced before study entry ranged from 1 to 6.
QoL Instruments
Three age-specific instruments were used to assess QoL among HIV-infected and uninfected patients enrolled in PACTG 219C, ie, 6 months to 4 years, 5 to 11 years, and 12 to 21 years. Primary caregivers completed questionnaires for children and adolescents. The instrument was based on a multidimensional conceptualization of QoL and included any of the following domains, depending on the age of the child: health perceptions, physical resilience, functional status, physical functioning, psychological functioning, social/role functioning, and symptoms.11, 16 Symptoms included items such as pain, gastrointestinal symptoms, respiratory symptoms, and constitutional symptoms (eg, fevers or loss of appetite) that might have been attributable to progressive disease, medication side effects, or intercurrent illness.
Prior analyses have supported the reliability and validity of using these instruments to measure health outcomes in this population.16 Examples of questions and the internal consistency of each domain (as measured with Cronbach's
) are described in the Appendix. The measure of social/role functioning included items designed to describe several latent constructs such as limited activity and days in the past month spent in bed; therefore, social/role functioning was considered an index rather than a scale, and Cronbach's
was not assessed as a measure of reliability for this domain.17 Limitations in school attendance were included in the adolescent social/role functioning index.
Outcome Measures
Our outcome measures were age-specific, standardized, domain scores of QoL. To calculate these domain scores, each domain was given a raw score computed as a simple algebraic sum.16 Each raw scale score was then transformed to a 0 to 100 scale with the following formula: transformed score = [(actual raw score lowest possible raw score)/(highest possible raw score lowest possible raw score)] x 100. These domain scores were transformed, or standardized, for each age group so that higher scores indicated better functioning for the following domains: health perceptions, physical resilience, functional status, physical functioning, psychological functioning, and social/role functioning. Higher scores for the HIV-related symptoms domain indicated fewer symptoms.
Statistical Analyses
Patient characteristics were compared by using t tests for continuous variables and
2 tests for categorical variables. We compared age-specific QoL domain scores according to infection status and alternative antiretroviral regimens by using t tests or analysis of variance in unadjusted analyses. Age-stratified, multivariate, linear regression models were constructed to assess the association of infection status with QoL domains with adjustment for demographic and social/environmental characteristics, including age, gender, race/ethnicity, year of enrollment, primary caregiver, educational level of primary caregiver, and negative life event score, on the basis of previous studies.11, 18, 19 We also constructed age-stratified, adjusted, analysis of variance models to assess the association of different treatment regimens with QoL domains. If significant differences were found, then we compared each pair of regimens with the Wald test, to determine the source of these differences. Covariates in these adjusted models were based on previous studies and included demographic and social/environmental characteristics (as described above), clinical data (CDC classification), and laboratory data (CD4+ cell percentage and viral load).11, 20 P values (2-tailed) of <.05 were considered statistically significant. All analyses were performed with Intercooled Stata 7.0 (Stata, College Station, TX).
| RESULTS |
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Infection Status and QoL
We compared demographic and social/environmental characteristics for 1847 infected and 712 uninfected children (Table 1). Because most uninfected children were enrolled at birth at the time of perinatal HIV exposure, the mean age of uninfected children was younger. Infected children were more likely to be female, to be black non-Hispanic, and to live with a primary caregiver who was not a biological parent. Conversely, uninfected children were more likely to be Hispanic and to live with a biological parent. In addition, primary caregivers of uninfected children 6 months to 4 years of age were less likely to provide information about their educational level, and uninfected children 5 to 11 years of age were found to have higher negative life event scores.
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In unadjusted analyses, primary caregivers of infected children 6 months to 4 years of age reported significantly lower health perceptions, physical resilience, functional status, and symptoms (Table 2). In adjusted analyses, only functional status scores remained significantly lower for HIV-infected children.
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For children 5 to 11 years of age, unadjusted analyses demonstrated significantly lower domain scores for health perceptions, physical resilience, and social/role functioning among infected children (Table 2). However, higher domain scores for psychological functioning were reported for infected children. In adjusted analyses, parents of infected children reported worse health perceptions, physical resilience, physical functioning, and social/role functioning. Uninfected children were reported to have worse psychological functioning in adjusted analyses. As described previously, uninfected children 5 to 11 years of age also reported higher negative life event scores, compared with infected children. In particular, the following life events occurred more often in families of uninfected children: family member left home (17% vs 9%; P = .006), loss of housing or had to move (16% vs 10%; P = .038), loss of health insurance (9% vs 4%; P = .034), separation of parents (9% vs 5%; P = .019), mother starting work (15% vs 7%; P = .002), change in financial status of parents (22% vs 13%; P = .003), and death in the family (23% vs 15%; P = .013).
We were unable to assess the impact of infection status among adolescents
12 years of age, because there were no uninfected children enrolled in this age group. However, mean domain scores were as follows: health perceptions, 79.3; physical functioning, 85.7; psychological functioning, 79.6; social/role functioning, 82.5; symptoms, 94.1.
Antiretroviral Regimen and QoL
Characteristics of children receiving different antiretroviral regimens are presented in Table 3. Overall, there were few significant differences in sociodemographic characteristics for children and adolescents receiving different antiretroviral regimens (except that more female subjects 511 years of age were receiving NRTIs); however, differences in treatment experience, or mean number of antiretroviral regimens, did exist in all age groups (the NRTI group had the least treatment experience). Children 5 to 11 years of age exhibited significant differences in mean negative life event scores (more negative life events in the NNRTI-treated group); children 5 to 11 years of age and adolescents 12 to 21 years of age exhibited differences in CDC clinical classification (more children with AIDS-defining illnesses in the PI and PI plus NNRTI treatment groups). CD4+ cell percentages and viral loads also varied according to treatment group for children 6 months to 4 years and 5 to 11 years of age. Therefore, severity of illness (CDC classification, CD4+ cell percentage, and viral load) and treatment experience varied depending on the type of antiretroviral regimen in this observational study.
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Comparisons of unadjusted mean domain scores for different antiretroviral regimens are shown in Table 4. In adjusted analyses controlling for sociodemographic variables and severity of illness, no significant differences were found for children 6 months to 4 years of age. However, children 5 to 11 years of age and adolescents 12 to 21 years of age in the no-antiretroviral treatment group had worse health perceptions than did those receiving antiretroviral agents. Adolescents 12 to 21 years of age were also found to have significant differences in symptoms in adjusted analyses. Again, those receiving no antiretroviral treatment had significantly worse symptoms, compared with those receiving any antiretroviral regimen.
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When antiretroviral regimens were compared with each other, there were no significant differences in health perceptions for children 5 to 11 years of age or adolescents 12 to 21 years of age. However, adolescents receiving PI plus NNRTI therapy had worse symptom scores than did those receiving PI therapy alone. In particular, adolescents receiving PI plus NNRTI therapy were significantly more likely than those receiving PI therapy to report the following symptoms: physical or bodily pain (14% vs 4%; P = .016), nausea/vomiting/abdominal or stomach pain (7% vs 1%; P = .011), diarrhea (14% vs 5%; P = .030), feeling dizzy/lightheaded (5% vs 1%; P = .040), fevers/night sweats/shaking/chills (9% vs 1%; P = .003), dry or painful mouth/trouble swallowing (5% vs 1%; P = .040), or chest pain/tightness (7% vs 0%; P = .002).
| DISCUSSION |
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Our study examined QoL outcomes among HIV-infected and uninfected children and adolescents with perinatal exposure. Our data set is unique in that we had a comparison group of children who were born to HIV-infected mothers and were subsequently found to be uninfected. This data set provides a much more direct and relevant comparison group than the general population, although we still found significant differences in race/ethnicity, type of primary caregiver, educational attainment, and total number of negative life events between infected and uninfected children. In addition, we were able to study the impact of different antiretroviral regimens on QoL outcomes for children, which has not been done before.
Overall, HIV infection was associated with a negative impact on QoL among children, with lower scores for functional status for children 6 months to 4 years of age and lower scores for health perceptions, physical resilience, physical functioning, and social/role functioning for children 5 to 11 years of age. Previous studies of adults that compared HIV-infected individuals with the general population showed similar findings, with lower scores for general health perceptions and physical functioning being reported for infected adults.2022 In contrast, we found lower psychological functioning scores among uninfected children 5 to 11 years of age. The greater number of negative life events might have contributed to this finding, although we attempted to adjust for this in our analysis. Alternatively, it may be that infected children have better access to support and social services from health care providers in HIV clinics. Selection bias also might have played a role, because uninfected children who are well usually are not monitored in pediatric HIV clinics and those who were brought regularly by their caretakers might have had greater psychosocial needs.
When different antiretroviral regimens (NRTI, NNRTI, PI, or PI plus NNRTI) were compared with each other for children 6 months to 21 years of age, no significant differences were found in health perceptions, physical resilience, functional status, social/role functioning, physical functioning, or psychological functioning across these groups. Our findings suggest that there is no evidence at this point to favor one type of antiretroviral regimen over another, on the basis of these QoL considerations. A study by Storm et al11 that evaluated QoL outcomes among children 5 to 18 years of age also demonstrated no significant differences for children receiving PI therapy versus non-PI therapy. In that study, however, information was not available at the time regarding specific types of antiretroviral regimens (such as NRTI versus NNRTI versus PI plus NNRTI).
We did find significant differences in reported symptoms for adolescents 12 to 21 years of age. Individuals receiving PI- plus NNRTI-containing regimens had worse symptoms, compared with those receiving PI-containing regimens. Although we attempted to control for potentially confounding variables, we might not have been able to adjust adequately for severity of illness in our analysis, with more children with progressive HIV disease in the PI plus NNRTI treatment group. Another potential explanation might be that therapy with 2 classes of antiretroviral agents resulted in adverse events associated with treatment that were additive, and thus worse symptoms were reported.
Interestingly, children who were not receiving any antiretroviral therapy reported worse QoL in 2 domains. Although the total number of children receiving no treatment was small, children 5 to 11 years of age were found to have worse health perceptions, whereas adolescents 12 to 21 years of age had worse health perceptions and symptoms. We think that the findings that those receiving any antiretroviral treatment had better health perceptions and fewer symptoms than did those receiving no antiretroviral treatment are reassuring. Antiretroviral therapy may indeed be associated with improved QoL among HIV-infected children and adolescents, similar to the experience among adults.2325
Our findings should be interpreted with several limitations in mind. First, this was a cross-sectional analysis of HIV-infected and uninfected children enrolled in a prospective observational study. Therefore, we could evaluate only the presence of associations between types of therapy and QoL domains and not their causality. Longitudinal analyses potentially could address this issue by evaluating how changes in antiretroviral regimens among children affect their QoL over time. Second, children with severe illness might have been more likely to receive one type of antiretroviral regimen than another. Although we attempted to adjust for severity of illness in our model, there might be additional important factors that were not included in these analyses.
Third, the total number of children in the no-treatment group was small (n = 17). Therefore, our power to detect a significant difference for this group, compared with the antiretroviral therapy groups, was limited. Nevertheless, we demonstrated significant persistent differences in unadjusted and adjusted analyses, which suggested that this small group of children was markedly different from the group of children receiving antiretroviral treatment. When we compared the total number of antiretroviral regimens they had received at the time of study entry, we noted that these children already had significant treatment experience, which suggests that the children receiving no antiretroviral treatment represented a selected group of children who failed therapy for unclear reasons or were nonadherent because of difficult circumstances, as reflected by their poor QoL. The direction of this relationship cannot be assessed in a cross-sectional analysis.
Fourth, parents and caregivers were the most common source of QoL assessments and might or might not have given accurate assessments of the children's QoL. Clearly, additional research identifying techniques to obtain preferences directly from children would be preferred when treatment decisions need to be considered. Finally, although we found statistically significant differences in QoL domain scores, the clinical significance of such differences was not assessed and should be addressed in additional QoL evaluations.
We conclude that HIV infection is associated with worse QoL among children and that antiretroviral therapy may be related to better QoL among infected children. We found no consistent differences between antiretroviral regimens. Future efforts should continue to focus on identifying opportunities to prevent pediatric HIV infection and to optimize QoL outcomes for children who are infected with HIV.
APPENDIX QoL Questionnaire
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NA indicates not available.
a Social/role functioning was considered an index, rather than a scale; therefore, Cronbach's
was not assessed as a measure of reliability for this domain.
| ACKNOWLEDGMENTS |
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This study was funded by the Pediatrics AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases and the Pediatric-Perinatal HIV Clinical Trials Network of the National Institute of Child Health and Human Development. Dr Lee was also supported in part by a grant from the Agency for Healthcare Research and Quality (grant K-08 HS013908-01 A1).
We thank Sandra Burchett, Rosemary Galvin, Nancy Karthas, Catherine Kneut, and Lynne Lewis from the Children's Hospital AIDS Program at Children's Hospital Boston and George Seage from the Harvard School of Public Health for their invaluable input. We also thank the children and their families for their participation in this research and the personnel at the following institutions involved in PACTG 219C: University of Medicine and Dentistry of New Jersey: P. Palumbo, P. Andrew, A. Dieudonne, B. Dashefsky; Robert Wood Johnson Medical School: S. Gaur, P. Whitley-Williams, A. Malhotra, L. Cerracchio; Harbor-University of California, Los Angeles, Medical Center: M. Keller, J. Hayes, A. Gagajena, C. Mink; Johns Hopkins University Pediatrics: N. Hutton, B. Griffith, M. Joyner, C. Kiefner; Baylor Texas Children's Hospital: F. Minglana, M. E. Paul, W. T. Shearer, C. D. Jackson; Sinai Children's Hospital: D. C. Johnson, D. Kowalski, B. Wolfe, D. Ryan; Columbia Presbyterian Medical Center and Cornell University New York Presbyterian Hospital: A. Higgins, M. Foca, P. LaRussa, A. Gershon; University of Miami: G. B. Scott, C. D. Mitchell, L. Taybo, C. Gamber; Children's Hospital and Research Center at Oakland: A. Petru, T. Courville, K. Gold, L. Johnson; Phoenix Children's Hospital: J. P. Piatt, J. Foti, L. Clarke-Steffen; University of North Carolina at Chapel Hill: T. Belho, B. Pitkin, J. Eddleman; Schneider Children's Hospital: V. R. Bonagura, S. J. Schuval, C. Colter; Harlem Hospital: E. J. Abrams, M. Frere, D. Calo, S. Champion; Children's Hospital at Downstate: E. Handelsman, H. J. Moallem, D. M. Swindell, J. M. Kaye; Jacobi Medical Center: M. Chin, K Dorio, A. Wiznia, M. Donovan; San Juan Hospital: M. Acevedo, M. Gonzalez, L. Fabregas, M. E. Texidor; Yale University School Of Medicine: W. A. Andiman, S. Romano, L. Hurst, J. de Jesus; State University of New York Upstate Medical University: L. B. Weiner, K. A. Contello, W. A. Holz, M. J. Famiglietti; State University of New York at Stony Brook: S. Nachman, D. Nikolic-Djokic, D. Ferraro, J. Perillo; Howard University: S. Rana, H. Finke-Castro, P. H. Yu, J. C. Roa; University of Florida Health Science Center, Jacksonville: M. H. Rathore, A. Khayat, K. Champion, S. Cusic; St Jude Children's Research Hospital, Memphis: P. M. Flynn, K. Knapp, N. Patel; Vanderbilt University Medical Center: G. Wilson; Department of Pediatrics, Washington University School of Medicine, St Louis: K. A. McGann, L. Pickering, G. A. Storch; Children's Hospital of Philadelphia: S. D. Douglas, G. Koutsoubis, R. M. Rutstein, C. A. Vincent: Charity Hospital of New Orleans and Earl K. Long Early Intervention Clinic: M. Silio, T. Alchediak, C. Boe, M. Cowie; Baystate Medical Center Children's Hospital: B. W. Stechenberg, D. J. Fisher, A. M. Johnston, M. Toye; Medical College of Georgia: C. S. Mani, S. Foshee, B. Kiean, S. Cobb; University of Maryland: J. Farley, K. Klipner; Cooper Hospital-University Medical Center; Children's Hospital Boston; University of California, Los Angeles, Medical Center; Children's Hospital of Los Angeles; Long Beach Memorial; Chicago Children's Memorial Hospital; Cook County Hospital; University of Chicago Children's Hospital; Women's and Children's HIV Program; University of California, San Francisco; Moffitt Hospital; University of California, San Diego, Mother, Child, and Adolescent HIV Program; Phoenix Children's Hospital; Duke University; New York University School of Medicine; Children's National Medical Center; Children's Hospital and Regional Medical Center; University of South Florida; Oregon Health and Science University; Children's Hospital of the King's Daughters; Lincoln Medical and Mental Health Center; Mount Sinai Medical Center; University of Illinois; Children's Hospital of Michigan; Children's Medical Center of Dallas; Los Angeles County Medical Center/University of Southern California; Children's Hospital, University of Colorado, Denver; North Broward Hospital District; University of Florida, Gainesville; University of Rochester Medical Center; University of Mississippi Medical Center; Medical College of Virginia; University of Puerto Rico, University Children's Hospital AIDS; St Christopher's Hospital for Children, Philadelphia; Bronx Lebanon Hospital Center; St Luke's/Roosevelt Hospital Center; Montefiore Medical-Albert Einstein College of Medicine; Metropolitan Hospital Center; University of Massachusetts Medical School; Connecticut Children's Medical Center; University of Alabama at Birmingham; University of South Alabama Medical Center.
| FOOTNOTES |
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Accepted Jun 1, 2005.
Address correspondence to Grace M. Lee, MD, MPH, Center for Child Health Care Studies, Department of Ambulatory Care and Prevention, 133 Brookline Ave, 6th Floor, Boston, MA 02215. E-mail: grace_lee{at}hphc.org
Financial Disclosure: Dr Hughes has received consultancies/grants from GlaxoSmithKline, Bristol-Myers Squibb, Roche, Tibotec, and Abbott. Drs Lee, Gortmaker, McIntosh, and Oleske have no disclosures to report.
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