ART indicates antiretroviral therapy; HAART, highly active antiretroviral
therapy; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, nonnucleoside
reverse transcriptase inhibitor; PATG, Pediatric AIDS Clinical Trials Group;
PI, protease inhibitor.
NRTI indicates nucleoside reverse transcriptase inhibitor; NNRTI, nonnucleoside
reverse transcriptase inhibitor; PI, protease inhibitor.
ART indicates antiretroviral therapy; HAART, highly active antiretroviral
therapy; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
Brogly S, Williams P, Seage GR, Oleske JM, Van Dyke R, McIntosh K, PACTG 219C Team FT. Antiretroviral Treatment in Pediatric HIV Infection in the United StatesFrom Clinical Trials to Clinical Practice. JAMA. 2005;293(18):2213-2220. doi:10.1001/jama.293.18.2213
Author Affiliations: Center for Biostatistics
in AIDS Research (Drs Brogly, Williams, and Seage), and Departments of Biostatistics
(Drs Brogly and Williams) and Epidemiology (Dr Seage), Harvard School of Public
Health, Boston, Mass; Department of Pediatrics, University of Medicine &
Dentistry of New Jersey, Newark (Dr Oleske); Department of Pediatrics, Tulane
University Health Sciences Center, New Orleans, La (Dr Van Dyke); and Division
of Infectious Diseases, Children’s Hospital Boston, Boston, Mass (Dr
Context Antiretroviral therapy (ART) for pediatric human immunodeficiency virus
(HIV) infection has evolved from simple nucleoside reverse transcriptase inhibitor
(NRTI) regimens to complex combination therapies based largely on evidence
from clinical trials. However, the integration of novel ART into the clinical
care of pediatric HIV infection has not been examined.
Objectives To describe changes in the treatment of pediatric HIV infection in the
United States from 1987-2003, to assess concordance of initial regimens with
US pediatric guidelines, and to identify predictors of the first regimen switch.
Design, Setting, and Participants The study population included 766 perinatally HIV-infected children
in the Pediatric AIDS Clinical Trials Group 219C cohort born before January
1, 2004, who had not participated in an ART clinical trial at 219C enrollment
or during follow-up.
Main Outcome Measures Proportion of children receiving specific ART regimens, proportion of
children initiating ART according to pediatric guidelines, and time to first
regimen switch (risk of switching).
Results Single and dual NRTI regimens were used most frequently through 1997.
In 1998, 2 years after protease inhibitors were approved for adult HIV infection
and at the time pediatric guidelines were issued, regimens of highly active
antiretroviral therapy including a protease inhibitor became most frequently
used. From 1998-2003, 22% of children initiated ART with a regimen not recommended
by pediatric guidelines. In multivariate regression, the risk of switching
decreased with age at ART initiation (hazard ratio [HR], 0.96; 95% confidence
interval [CI], 0.94-0.99) and increased with year of initiation (HR, 1.28;
95% CI, 1.23-1.33). The risk of switching was higher in children who started
with 1 NRTI (HR, 8.05; 95% CI, 5.80-11.18), 2 NRTIs (HR, 4.08; 95% CI, 3.08-5.40),
or an unconventional regimen (HR, 6.23; 95% CI, 3.36-11.54) vs children who
started with a protease inhibitor–containing regimen; and in children
who initiated ART at CD4 T lymphocyte percentages less than 15 vs 15 or greater
(HR, 2.90; 95% CI, 1.03-8.13).
Conclusions There was a short lag between the identification of novel ART and its
adoption in the pediatric community. A variety of regimens were used, including
some unorthodox therapies. Important predictors of first regimen switch were
Antiretroviral therapy (ART) for pediatric human immunodeficiency virus
(HIV) infection has evolved from the single or dual nucleoside reverse transcriptase
inhibitor (NRTI) regimens of the 1980s and early 1990s to today’s complex
regimens of NRTI in combination with protease inhibitors (PIs) and/or nonnucleoside
reverse transcriptase inhibitors (NNRTIs). Changes in the treatment of pediatric
HIV infection were driven by evidence from randomized controlled trials in
HIV-infected adults,1- 6 a
small number of pediatric trials,7- 10 and
nonexperimental pediatric studies.11- 14 No
studies have examined how novel therapies have been integrated into the clinical
care of pediatric HIV infection.
Since 1998, the US Working Group on Antiretroviral Therapy and the Medical
Management of HIV-Infected Children has published guidelines for the use of
combination ART for pediatric HIV infection.15 Current
pediatric guidelines recommend a regimen of 2 NRTIs in combination with a PI
or an NNRTI.16 These guidelines exist to aid
the practicing physician and are not meant to supplant clinical decision-making.
To date, concordance between the US pediatric guidelines and treatment in
clinical practice has not been assessed.
As HIV becomes a treatable disease, it is becoming increasingly important
to take a long-term strategic approach to initial and subsequent ART. Quantifying
the frequency of treatment switches provides an estimate of the rate at which
regimens are failing or not tolerated.17 We
identified only 1 study of ART use in HIV-infected children from 6 US sites
that reported increases in use of highly active antiretroviral therapy (HAART)
and frequent regimen changes from 1998 through 2000.18
The objectives of this study were to describe changes in the treatment
of pediatric HIV in the United States from 1987 to 2003; to determine initial
treatment choices, including the concordance between the US pediatric ART
guidelines and clinical practice; and to identify predictors of first regimen
The source population for this study was the Pediatric AIDS Clinical
Trials Group (PACTG) 219C cohort. All children born to an HIV-positive mother,
whether infected or uninfected, younger than 24 years, and receiving care
at a PACTG site were eligible. The PACTG 219C cohort has been enrolling and
following up children since September 2000. PACTG 219C was a revised version
of PACTG 219—a protocol initiated in 1993 to study the long-term effects
of in utero ART exposure and complications of HIV infection in children.19 Children eligible for the present study must have
been perinatally HIV infected, born before January 1, 2004, and must not have
participated in an ART clinical trial at 219C enrollment or during follow-up.
Although the latter criterion excluded roughly two thirds of perinatally infected
children, it was essential to allow investigation of trends in the treatment
of pediatric HIV infection in clinical practice. The institutions obtained
approval from their respective review boards for human research, and each
child’s parent or guardian provided written informed consent.
At 219C enrollment, medical and clinical histories and lifetime ART
use including start and stop dates were abstracted from clinical records,
CD4 T lymphocyte percentages and HIV viral loads were measured, and sociodemographic
information was obtained. Information on race/ethnicity was volunteered by
each child and/or guardian. Use of ART, HIV immunological and virological
parameters, and clinical diagnoses were recorded at follow-up visits every
3 months. CD4 percentages and HIV viral load at ART initiation and by calendar
year also were obtained from PACTG 219 when available; most children initiated
ART before 219C enrollment and the 219C protocol did not collect information
on CD4 percentages or viral load prior to enrollment. Thus, measures at ART
initiation were unavailable for many children.
We used the following ART regimen classification: 1 NRTI, 2 NRTIs, 3
or more NRTIs, HAART (3 or more drugs from at least 2 classes) including a
PI, HAART including an NNRTI, HAART including a PI plus an NNRTI, and other.
Zidovudine prophylaxis taken in the first 6 weeks of life to prevent HIV infection
was not counted as a regimen. The duration of use of each regimen was constructed
from the start and stop dates of lifetime ART use. When examining the number
of unique drug regimens, individual drugs rather than drug classes were considered.
To examine trends in ART use by calendar time, the proportion of children
receiving each of the above regimens from 1987 (the earliest date of ART use
in the study population) through 2003 was determined. If a child used more
than 1 regimen in a given year, 1 regimen was randomly selected. The use of
specific drugs, CD4 percentages, and viral load by calendar year also were
Concordance between first regimens and US pediatric guidelines was assessed
in children who initiated ART at 11 years or younger and on or after April
17, 1998—the date on which the pediatric guidelines for HIV infection
in the HAART era were published (Table 1).15 The upper age limit was used to ensure children were
treated according to pediatric, not adult and adolescent, guidelines. The
first regimen was classified according to the pediatric guidelines in effect
at the time each child started therapy. The guidelines classified initial
regimens as “strongly recommended,” “alternative,”
“secondary alternative,” “special circumstance,” and
“not recommended.” The proportion of children who initiated therapy
in each regimen category was reported. Children who started with a regimen
that did not correspond to one of the pediatric guideline categories were
classified as “other.”
To identify trends in the first, second, and third ART regimens and
to account for the temporal availability of ART, children were classified
into 4 birth cohorts. Birth cohort 1980-1990 was the period during which zidovudine
was the only US Food and Drug Administration (FDA)–approved ART for
HIV or AIDS; birth cohort 1991-1995 was the period during which additional
NRTIs became available; birth cohort 1996-1999 reflected the advent of HAART,
when PIs and NNRTIs were approved and began to be used; and birth cohort 2000-2003
reflected widespread use of PIs and NNRTIs. Dates of FDA approval of initial
drugs in each class are provided in Table 1.
The first, second, and third regimens and duration of use of each regimen
by birth cohort were determined.
Multivariate Cox proportional hazards regression was used to identify
predictors of time to first regimen switch. Variables considered included
sex, race/ethnicity, age at ART initiation, calendar year of ART initiation,
the first ART regimen, ART adherence at cohort enrollment, and whether the
child lived in a state with an AIDS Drug Assistance Program. Additional models
were constructed including CD4 percentages at the time of ART initiation for
children for whom these data were available. There were too few children with
HIV viral load measured at ART initiation to include this variable. The validity
of the proportional hazards assumption was assessed, and no marked violations
were identified. Analyses were performed using SAS version 8.2 (SAS Institute
Inc, Cary, NC); P<.05 was used to determine statistical
Of 2399 perinatally HIV-infected children enrolled in PACTG 219C between
September 2000 and April 2004, 1633 (68.1%) participated in an ART clinical
trial and thus were excluded. The remaining 766 children in the study population
were recruited from 79 institutions in 25 states across the United States.
The study population was significantly younger, more likely to be non-Hispanic
black and less likely to be Hispanic, and less likely to have CD4 lymphocyte
percentages in the lower range than ART trial participants (Table 2). At 219C enrollment, the participants’ ages ranged
from 1.2 months to 21.9 years, with a mean age of 8.1 years.
Figure 1 provides the proportion
of children receiving each ART regimen by year. Dual NRTI regimens began to
be used in 1993 and became the most frequently used regimens in 1996-1997.
In 1998—2 years after the implementation of PIs for adult HIV infection—regimens
of HAART including a PI became the most frequently used. In 2003, 51.3% of
children were receiving HAART including a PI; 12.3% were receiving HAART including
an NNRTI; 16.3% were receiving HAART including a PI plus an NNRTI; 12.5% were
receiving single, dual, and triple NRTIs; and 3.3% were receiving unconventional
regimens (ie, 1 NRTI plus 1 PI, 1 NRTI plus 1 NNRTI, PI only). After 2000,
the most frequently used regimen was either combination lamivudine, stavudine,
and nelfinavir or combination lamivudine, zidovudine, and nelfinavir, with
18.7% and 13.6% of children taking one of these regimens in 2000 and 2003,
respectively. The increased proportion of children receiving HAART was accompanied
by increases in CD4 percentages (<15: 20.0%, 20.0%, 18.3%, 9.7%, and 7.4%
in 1997, 1998, 1999, 2000, and 2003, respectively) and by decreases in HIV
viral load (>10 000 copies/mL: 75.0%, 60.0%, 77.8%, 32.1%, and 23.2%).
Trends in individual drug use by calendar time are shown in Figure 2. Zidovudine was the most frequently
used NRTI in the early years of the epidemic, reaching a peak of 90.4% in
1991 and decreasing to around 35% in 1999 as other NRTIs became available.
The use of didanosine also decreased after its peak of 51.3% in 1996. Stavudine
and lamivudine were the most frequently used NRTIs (approximately 55%) from
1998 onward. The use of both nevirapine and efavirenz steadily increased following
FDA approval in 1996 and 1998, respectively, with efavirenz becoming the most
frequently used NNRTI in 2002. However, less than 20% of children were receiving
either drug. The uptake of PIs was steady; nelfinavir was the most frequently
used PI from 1998-2002 but declined after its peak of 38.4% in 1999. In 2003,
boosted lopinavir was the most frequently used PI (28.4%), followed in frequency
by nelfinavir (27.3%).
In 2000, 20% of children initiated ART with combination lamivudine,
zidovudine, and nelfinavir, and 20% initiated ART with combination lamivudine,
stavudine, and nelfinavir. The proportion who initiated ART with combination
lamivudine, zidovudine, and boosted lopinavir has increased since 2001 (5.3%)
to become the most frequent initial regimen (30.0%) in 2003.
Concordance between the first regimens of the study population and pediatric
guidelines was assessed in 261 children who started therapy after the guidelines
were published (Table 1). These 261
children initiated therapy with the following pediatric guideline–classified
regimens: “strongly recommended” (49.0%), “alternative”
(14.6%), “secondary alternative” (8.8%), “special circumstance”
(5.4%), “not recommended” (7.3%), and “other” (14.9%).
The regimens of the 19 children who initiated a “not recommended”
regimen included 1 NRTI (84.2%), 1 NNRTI (5.3%), 3 NRTIs (including both zidovudine
and stavudine) (5.2%), and 1 PI (5.3%). The regimens of the 39 children who
initiated a regimen classified as “other” included HAART with
a PI plus an NNRTI (66.7%), HAART with an NNRTI but not the recommended one
(10.3%), HAART with a PI but not the recommended one (7.7%), 1 NRTI and 1
PI (5.1%), 3 NRTIs but not the recommended combination (5.1%), 1 NRTI and
1 NNRTI (2.6%), and 1 NNRTI and 1 PI (2.6%).
Among the 4 birth cohorts, 0.5% of cohort 1980-1990, 7.3% of cohort
1991-1995, 27.7% of cohort 1996-1999, and 50.0% of cohort 2000-2003 used zidovudine
prophylaxis in the first 6 weeks of life. The first, second, and third regimens
of each birth cohort were examined, and key findings are summarized in Figure 3. Most of birth cohort 1980-1990 initiated
therapy with 1 NRTI (66.1%), mainly zidovudine, which gradually decreased
to 11.5% in birth cohort 2000-2003 (Figure 3A).
HAART including a PI became the most frequently used first regimen in birth
cohort 1996-1999 (37.4%), increasing to 61.5% of birth cohort 2000-2003. In
the earlier birth cohorts, children frequently switched between single and/or
dual NRTI regimens, with a small number returning to single or dual NRTI regimens
after HAART. In contrast, none of birth cohort 2000-2003 switched to single
or dual NRTIs after HAART. Forty-one percent of birth cohort 1980-1990 used
HAART including a PI by their third regimen, which increased to almost 90%
of birth cohort 2000-2003 (Figure 3B).
The median age at the initiation of ART decreased from 5.8 years in the 1980-1990
birth cohort to 2.4 months in the 2000-2003 cohort, as did the median age
at initiation of HAART including a PI. Age at ART initiation decreased irrespective
of the availability of ART, but the decrease in age at first PI use was affected
by the availability of PIs. The median number of regimens used was 4 (10th,
90th percentiles: 1, 9) in birth cohort 1980-1990, 4 (10th, 90th: 1, 10) in
birth cohort 1991-1995, 2 (10th, 90th: 1, 6) in birth cohort 1996-1999, and
2 (10th, 90th: 1, 3) in birth cohort 2000-2003. Five children (2.2%) of birth
cohort 1980-1990, 5 children (1.8%) of birth cohort 1991-1995, 1 child (0.5%)
of birth cohort 1996-1999, and 2 children (2.5%) of birth cohort 2000-2003
never initiated ART.
Eleven children died from HIV infection or a related diagnosis, 10 from
birth cohort 1980-1990 and 1 from birth cohort 1991-1995. The median age of
death was 14.6 years (10th, 90th percentiles: 11.9, 19.2). All 11 children
were ART experienced, with a median age of ART initiation of 7.1 years (10th,
90th: 0.5, 14.0).
Six hundred six (80.5%) of the 753 children receiving ART switched from
a first to a second regimen. The median time to first regimen switch decreased
from 31.3 months in the 1980-1990 birth cohort to 13.8 months in the 2000-2003
cohort. The unadjusted hazard ratio (HR) for a first regimen of 1 NRTI, 2
NRTIs, or other ART (Table 3) dramatically
increased when adjusted for other covariates in the multivariate model, primarily
because of confounding by year of ART initiation. Thus, we focus on the multivariate
results. As shown, male participants had a higher risk of switching—or
shorter time to switch—than female participants (HR, 1.17; 95% confidence
interval [CI], 1.00-1.38). Risk of switching significantly decreased (ie,
a significantly longer time to switch) with age (years) at ART initiation
(HR, 0.96; 95% CI, 0.94-0.99) and significantly increased (ie, a significantly
shorter time to switch) with calendar year of ART initiation (HR, 1.28; 95%
CI, 1.23-1.33). The first regimen was associated with the likelihood of switching:
children who initiated therapy with 1 or 2 NRTIs or an unconventional regimen
had a significantly higher risk of switching (ie, shorter time to switch)
than those who initiated therapy with HAART including a PI. There was no significant
difference in the risk of switching among children who initiated ART with
3 or more NRTIs or HAART including an NNRTI or a PI plus an NNRTI vs those
who initiated therapy with HAART including a PI. Adherence to ART and living
in a state with an AIDS Drug Assistance Program were not associated with switching,
did not change the other parameter estimates, and therefore were not retained
in the model.
The likelihood of switching was examined in 39 children for whom CD4
percentages were available at ART initiation. In this multivariate model (adjusted
for a first regimen of 1 NRTI, 2 NRTIs vs other, and ART initiation at 3 years
or younger vs other), children who initiated ART at CD4 percentages less than
15 had a significantly higher risk of switching (ie, a shorter time to switch)
than did children who initiated ART with CD4 percentages of 15 or greater
(HR, 2.90; 95% CI, 1.03-8.13).
This study describes changes in the treatment of pediatric HIV infection
in the United States from 1987 through 2003. There was a short lag between
the identification of novel ART—including new drugs and drug combinations—and
its adoption in the pediatric community; both ritonavir and nelfinavir were
approved for children in 1997 and were in widespread use the following year.
Pediatricians involved in ART clinical trials treated the children in our
study population, which probably enhanced the transfer of research to clinical
practice. Some children who initiated dual NRTI before the HAART era continued
to have good immunological and clinical profiles, which thwarted the need
to switch to a more potent regimen.10 Further,
the uptake of PIs in 1998 corresponded to the publication of the pediatric
guidelines for combination ART.15 Thus, the
clinicians, patients, and caregivers may have been reluctant to use novel
treatment in the absence of recommendations for use in children.
To our knowledge, this is the first study to examine concordance between
the US pediatric ART guidelines16 and clinical
practice. We found that most clinicians of the collaborating institutions—of
which the majority were university affiliated HIV clinics—followed pediatric
guidelines. However, since publication of the pediatric guidelines in 1998,
22% of children initiated therapy with a regimen not recommended by the guidelines,
and a small proportion was receiving unorthodox treatment at any time in therapy.
Children who initiated therapy with these unorthodox regimens had a shorter
time to switch than did those who initiated therapy with HAART plus a PI.
A shorter time to switch might affect prognosis because of the increased exposure
to multiple drugs and drug classes, the consequent development of resistance,
and the reduction of future therapy options.16 The
relatively common use of nonstandard regimens may reflect some children’s
intolerance of standard therapy or the willingness of this group of physicians
to try unorthodox regimens.
Because a key objective of this study was to describe and assess the
treatment of pediatric HIV infection in clinical practice, the study population
was restricted to children in the PACTG 219C cohort who were not participants
in ART clinical trials. Although there was no difference in the virological
status of the 2 groups, the study population was younger, more likely to be
black and less likely to be Hispanic, and less likely to have CD4 lymphocyte
percentages in the lower range than were children who participated in ART
clinical trials. Furthermore, the clinical sites were university-affiliated
institutions, which may differ from other HIV clinics. As a result, our findings
may not be generalizable to all HIV-infected children. Nonetheless, 766 children
from 79 institutions in 25 states across the United States constituted our
study population, and therefore their ART experience should validly characterize
clinical practice in these university settings.
Although not statistically significant, time to first regimen switch
was shorter in male vs female participants. Studies in HIV-infected adults
have found that women have lower HIV RNA levels than men with comparable CD4
cell counts,22,23 and this was
observed in a study of HIV-infected infants.24 If
this phenomenon is in fact true of the pediatric population and clinicians
primarily are basing treatment initiation and switches on HIV RNA levels,
then this could explain our observed association. Levels of HIV RNA at ART
initiation were unavailable for most of the study population, and therefore
we were unable to examine this association. The role of sex, HIV RNA, and
ART should be studied further; the adult guidelines propose considering lower
HIV RNA thresholds when initiating therapy in women with CD4 cell counts greater
than 350 cells/μL.25
Others have reported that poor ART adherence is associated with an increased
likelihood of virological failure26,27 and
disease progression,27 which could warrant
a change in therapy. In our study, we found no association between switching
and ART adherence. Our adherence data concerned missed doses in the past 3
days and was measured at cohort enrollment, which was after ART initiation
for many children and may have misclassified ART adherence prior to switching.
Time to first regimen switch decreased with calendar year of ART initiation.
Children who initiated ART in the era of viral load monitoring, a larger selection
of treatments, and more potent therapies had a shorter time to first regimen
switch. Unfortunately, the 219C protocol did not record reasons for treatment
switch. While we have speculated that most switches were due to virological,
immunological, or clinical failure, other reasons such as drug toxicity and
palatability, age appropriateness of formulations, number of pills or volume
of liquid, frequency of dosing, and availability of new ART also may have
prompted a regimen switch.
A European survey conducted in 1998 found that most pediatric HIV physicians
delayed therapy until disease progression—evident through symptoms,
low CD4 cell counts, or high viral load—was apparent.28 In
our study, children who began ART when severely immunosuppressed (CD4 percentages
<15) had a significantly shorter time to first regimen switch than children
who were immunocompetent or moderately immunosuppressed at initiation. Studies
conducted in adults also have found that lower CD4 cell counts and higher
viral load have been associated with switching.17,29,30 Although
our analysis included children from all birth cohorts and who initiated ART
at varying ages, our findings on CD4 percentages were based on a small number
of children and may not be generalizable to the larger pediatric population.
In sum, this study describes changes in the treatment of pediatric HIV
infection in US children from 1987 through 2003. We identified demographic
differences in children who were participating in ART clinical trials and
in those who were not, as well as a short lag in the uptake of novel therapies
in this latter group of children. The use of unorthodox regimens not recommended
by the US pediatric guidelines was relatively common, and was related to a
shorter time to first regimen switch. Younger age at ART initiation, recent
ART initiation, immunosuppression at ART initiation, and initial therapy of
1 or 2 NRTIs were significantly associated with a shorter time to first regimen
switch. Monitoring and documenting ART use in HIV-infected children can provide
important insight regarding the clinical care of this population.
Corresponding Author: Susan Brogly, PhD,
Center for Biostatistics in AIDS Research, Harvard School of Public Health,
651 Huntington Ave, FXB-607, Boston, MA 02115-6017 (email@example.com).
Author Contributions: Dr Brogly had full access
to all of the data in the study and takes responsibility for the integrity
of the data and the accuracy of the data analysis.
Study concept and design; critical revision of the
manuscript for important intellectual content: Brogly, Williams, Seage,
Oleske, Van Dyke, McIntosh.
Acquisition of data: Oleske, Van Dyke, McIntosh.
Analysis and interpretation of data: Brogly,
Williams, Seage, Oleske.
Drafting of the manuscript: Brogly.
Statistical analysis: Brogly, Williams.
Obtained funding: Oleske.
Administrative, technical, or material support:
Brogly, Oleske, Van Dyke.
Study supervision: Van Dyke, McIntosh.
Financial Disclosures: None reported.
Funding/Support: This study was funded by the
US National Institute of Allergy and Infectious Diseases and the National
Institute of Child Health and Human Development. This work was further supported
by Center for Biostatistics in AIDS Research at the Harvard School of Public
Health (the statistical and data analysis center of the Pediatric AIDS Clinical
Trials Group) under the National Institute of Allergy and Infectious Diseases
cooperative agreement 5 U01 AI41110.
Role of the Sponsors: The US National Institute
of Allergy and Infectious Diseases and the National Institute of Child Health
and Human Development were involved in the design, data collection, and conduct
of protocol 219C but were not involved in the present analysis, the interpretation
of the data, the writing of the manuscript, or the decision to submit for
Contributing PACTG 219C Site Personnel:University of Medicine & 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-UCLA 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; The Columbia Presbyterian Medical Center & 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 & 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; The 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; SUNY Upstate Medical University: L.
B. Weiner, K. A. Contello, W. A. Holz, M. J. Famiglietti; SUNY 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 Children’s Hospital:
K. A. McGann, L. Pickering, G. A. Storch; The Children’s
Hospital of Philadelphia: S. D. Douglas, G. Koutsoubis, R. M. Rutstein,
C. A. Vincent; Charity Hospital of New Orleans & 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 Medical Center: J. Farley, K. Klipner.
PACTG Centers: Cooper Hospital–University Medical
Center; Children’s Hospital Boston; Boston Medical Center; UCLA Medical
Center; Children’s Hospital of Los Angeles; Long Beach Memorial; Chicago
Children’s Memorial Hospital; Cook County Hospital; The University of
Chicago Children’s Hospital; Mount Sinai Medical Center, Womens &
Children’s HIV Program; UCSF, Moffitt Hospital; UCSD Mother, Child &
Adolescent HIV Program; Phoenix Children’s Hospital; Duke University;
New York University School of Medicine/Bellevue Hospital; Children’s
National Medical Center; Children's Hospital and Regional Medical Center,
Washington, DC; University of South Florida; Oregon Health and Science University;
Children’s Hospital of the King’s Daughters; Lincoln Medical &
Mental Health Center; University of Illinois; Children’s Hospital of
Michigan; Children’s Medical Center of Dallas; Los Angeles County Medical
Center/USC; Children’s Hospital, University of Colorado, Denver; North
Broward Hospital District; University of Florida at Gainesville; University
of Rochester Medical Center; University of Mississippi Medical Center; Medical
College of Virginia; University of Puerto Rico, University Children’s
Hospital AIDS Program; St Christopher’s Hospital for Children, Philadelphia;
Bronx Lebanon Hospital Center; St Luke’s/Roosevelt Hospital Center;
Montefiore Medical–AECOM; Metropolitan Hospital Center; University of
Massachusetts Medical School; Connecticut Children’s Medical Center;
University of Alabama at Birmingham; University of South Alabama; The Medical
Center, Pediatric Columbus, Georgia; Incarnation Children’s Center,
New York; St Joseph’s Hospital and Medical Center, New Jersey; Children’s
Hospital of Oakland; Emory University Hospital; Ruiz Arnau University Hospital;
Medical University of South Carolina; Children’s Hospital at Albany
Medical Center; Columbus Children’s Hospital; Public Health Unit of
Palm Beach County; Children’s Hospital of Los Angeles.
Acknowledgment: We thank the children and families
for their participation in PACTG 219C and the individuals and institutions
involved in the conduct of 219C.