Published online July 2, 2007
PEDIATRICS Vol. 120 No. 1 July 2007, pp. 100-109 (doi:10.1542/peds.2006-2052)
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ARTICLE

Trends in Opportunistic Infections in the Pre–and Post–Highly Active Antiretroviral Therapy Eras Among HIV-Infected Children in the Perinatal AIDS Collaborative Transmission Study, 1986–2004

Steven R. Nesheim, MDa, Bill G. Kapogiannis, MDa,b, Minn M. Soe, MD, MPHc, Kevin M. Sullivan, PhD, MPHc, Elaine Abrams, MDd, John Farley, MD, MPHe, Paul Palumbo, MDf, Linda J. Koenig, PhDg and Marc Bulterys, MD, PhDg

a Departments of Pediatrics
b Medicine, Division of Infectious Diseases, Emory University School of Medicine
c Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
d Department of Pediatrics, Harlem Hospital Center, New York, New York
e Department of Pediatrics, University of Maryland, Baltimore, Maryland
f Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Newark, New Jersey
g Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVE. We sought to determine the impact of highly active antiretroviral therapy on the incidence and prevalence of opportunistic infections in HIV-infected children.

METHODS. Children born from 1986 to 1998 were monitored until 2004 in the Perinatal AIDS Collaborative Transmission Study, sponsored by the Centers for Disease Control and Prevention. We determined the pre–highly active antiretroviral therapy and post–highly active antiretroviral therapy (before and after January 1, 1997, respectively) incidence rates of opportunistic infections among HIV-infected children and characterized the temporal decreases in percentages of CD4+ cells and the mortality rates among patients with and those without incident opportunistic infections.

RESULTS. The overall opportunistic infection incidence declined from 14.4 to 1.1 cases per 100 patient-years; statistically significant reductions were seen in the incidence of the most common opportunistic infections, including Pneumocystis jiroveci pneumonia (5.8 vs 0.3 cases per 100 patient-years), recurrent bacterial infections (4.7 vs 0.2 cases per 100 patient-years), extraocular cytomegalovirus infection (1.4 vs 0.1 cases per 100 patient-years), and disseminated nontuberculous mycobacterial infection (1.3 vs 0.2 cases per 100 patient-years). Kaplan-Meier analysis of time from birth to the first opportunistic infection illustrated more-rapid acquisition of opportunistic infections by HIV-infected children born in the pre–highly active antiretroviral therapy era than by those born later. In the first 3 years of life, there was a faster decline in the percentage of CD4+ cells among children with opportunistic infections. The mortality rate was significantly higher among children with opportunistic infections.

CONCLUSIONS. Reduction in the incidence of opportunistic infections and prolongation of the time to the first opportunistic infection were noted during the post–highly active antiretroviral therapy era. Children who experienced opportunistic infections had higher mortality rates than did those who did not. Younger children (<3 years) who experienced opportunistic infections had faster declines in percentages of CD4+ T cells.

Key Words: pediatric HIV/AIDS • opportunistic infections • highly active antiretroviral therapy

Abbreviations: CDC—Centers for Disease Control and Prevention • CMV—cytomegalovirus • HAART—highly active antiretroviral therapy • NTM—nontuberculous mycobacteria • OI—opportunistic infection • PACTG—Pediatric AIDS Clinical Trials Group • PACTS—Perinatal AIDS Collaborative Transmission Study • PACTS-HOPE—Perinatal AIDS Collaborative Transmission Study-HIV Follow-up after Perinatal Exposure • PCP—Pneumocystis jiroveci pneumonia • PSD—Pediatric Spectrum of Disease • RBI—recurrent bacterial infection

The introduction of protease inhibitors and nonnucleoside reverse transcriptase inhibitors for treatment of HIV infections made possible the use of antiretroviral combinations known as highly active antiretroviral therapy (HAART). Since the implementation of HAART became widespread, declines in mortality rates for HIV-infected adults1–4 and children5,6 have been well documented. The incidence rates of AIDS and specific opportunistic infections (OIs) have also declined.1,7–9 Declining OI incidence rates in children have been described10–13 but not in a birth cohort. Along with declining OI incidence rates, immunologic improvements have allowed individuals to discontinue both primary and secondary prophylactic measures for certain OIs; this approach has now become standard practice.2,14,15

The Centers for Disease Control and Prevention (CDC)-sponsored Perinatal AIDS Collaborative Transmission Study (PACTS) and its successor study, Perinatal AIDS Collaborative Transmission Study-HIV Follow-up after Perinatal Exposure (PACTS-HOPE), followed from birth until 2004 a large, multicenter cohort of perinatally HIV-infected children born in the United States between 1986 and 1998. This period spans a number of major milestones in pediatric HIV/AIDS management and allowed us to examine the decline in the incidence of OIs among HIV-infected children.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Study Subjects and Design
PACTS is a CDC-sponsored, multicenter, prospective cohort study of mother-to-child HIV transmission and the natural history of HIV disease, enrolling HIV-exposed infants and their mothers in 4 US cities. The study was described in detail previously.16,17 Each site began enrollment as follows: New York City, 1986; Baltimore, 1989; Atlanta and Newark, 1990. Follow-up monitoring of mother-infant pairs was discontinued on September 30, 1999, 1 year after enrollment was terminated. HIV-infected PACTS enrollees were enrolled subsequently in a new follow-up study (PACTS-HOPE) that began in 2000. Clinical data on PACTS-HOPE enrollees were collected for the period between the 2 studies (October 1, 1999, to March 1, 2000) and then every 6 months.18,19 Follow-up monitoring continued until April 2004. Hereafter, PACTS and PACTS-HOPE enrollees collectively are referred to as the study cohort. An analysis was undertaken to determine the incidence and prevalence of HIV-related OIs and the impact of HAART on these events.

Definition of HAART Era
At each study visit, data were collected on the use of any antiretroviral medications since the previous visit. HAART was defined as the receipt of combination antiretroviral therapy that consisted of ≥3 antiretroviral medications. The regimens usually consisted of 2 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor; a few children received 3 nucleoside reverse transcriptase inhibitors. OIs that occurred during the pre-HAART and post-HAART eras were defined as those that occurred before and after January 1, 1997, respectively. The reasons for the choice of this date as the cutoff point are twofold. First, 1997 was the year in which many centers throughout the United States were initiating HAART for HIV-infected children.5 Second, the exact date of HAART initiation varied according to site and caregiver, necessitating an arbitrary estimate. We determined the most relevant date for our entire HIV-infected cohort by using Kaplan-Meier analysis for time to initiation of HAART, analyzing several potential dates while choosing the date whose corresponding curve allowed minimal misclassification of patients. This date was confirmed by analyzing the frequency distribution of HAART initiation according to calendar year among children born before January 1, 1997, and those born after January 1, 1997, which showed that 1997 was the year in which most children (42%) started HAART. Of the remainder, 25% started HAART in 1996 or earlier and 33% in 1998 or later.

The following variables were analyzed for subjects with OIs in the pre-HAART and post-HAART eras: patient demographic characteristics, antiretroviral treatment, immunologic status (absolute CD4+ cell count and percentage), and virologic status (plasma HIV RNA quantification). Except where noted otherwise, patients could contribute data more than once and, if they were born in the pre-HAART era, to both time periods.

Definition of OIs
OIs were defined as infectious illnesses (including recurrent bacterial infections [RBIs]) on the list of AIDS-qualifying conditions included in the revised CDC AIDS case definition.20

Incidence Rate Calculation
The incidence rate of OI first was calculated for the pre-HAART and post-HAART periods by using a person-time approach and then was stratified according to age, gender, and race, to yield stratum-specific incidence rates with stratum-specific rate ratios and Mantel-Haenszel adjusted incidence rate ratios with 95% confidence intervals. Disease-specific incidence rates were calculated by censoring follow-up data after the first occurrence of that specific OI for a given patient; however, follow-up monitoring continued for that patient in other disease categories until a different OI occurred or, if no additional OI occurred, the end of follow-up monitoring was attained. Stratum-specific incidence rates were calculated by including only the first OI for a given patient, censoring the follow-up data at that time. If a zero cell resulted because of the lack of an OI, then the confidence interval with exact mid-P method was used to obtain an upper confidence limit (Computer Programs for Epidemiologic Analysis).21 The follow-up times for the pre-HAART and post-HAART eras were the total numbers of months all subjects lived before and after January 1, 1997, respectively.

Time to First OI
Survival analysis was used to compare the time until the development of the first OI among HIV-infected children born before or after January 1, 1997. For this analysis, subjects born in the pre-HAART era who were monitored beyond January 1, 1997, had their follow-up times censored after January 1, 1997. Kaplan-Meier and adjusted survival plots controlling for gender and race were constructed for comparisons between the 2 groups described previously. To determine the effect of the post-HAART era on the time to development of a first OI, we used Cox proportional-hazard analysis to yield the final model, after testing interaction terms and assessing confounding by other covariates such as gender and race. When constructing the models, we applied multicolinearity and regression diagnostic tests to evaluate model fit.

Immunologic and Virologic Status
Immunologic status was assessed as the percentage of CD4+ cells, and virologic status was assessed through plasma HIV RNA quantification (HIV viral load). Percentage of CD4+ cells was used instead of the absolute CD4+ cell count for the analysis because the former is generally accepted as a more stable parameter, particularly during the early years of life, when there can be large fluctuations in normal absolute CD4+ cell count ranges.22 To determine the trends for these parameters, their distributions according to age were estimated through linear regression analysis with 95% confidence intervals, as described previously by Denny et al.22 Data chosen for this analysis were limited to children 0 through 72 months of age; this interval was selected because it included nearly all of the OI occurrences (195 of 211 cases; 92%). Data from the same patient at different ages were identified, and a single result was selected randomly for analysis; this approach was used to avoid overrepresentation of individual data, which might be highly correlated. The comparison of the slopes of the 2 regression lines (children with OIs and children without OIs) was analyzed through assessment of an interaction term in the linear regression model.

Mortality Analysis
Deaths of HIV-infected children were analyzed through survival analysis, to compare the time until death between children with and without OIs. Subjects born in the pre-HAART era who were monitored beyond January 1, 1997, had their follow-up times censored after January 1, 1997. Cox proportional-hazard analysis was also performed, to explore the contribution of other covariates, such as gender, race, and clinical sites of care.

Statistical Analyses
Demographic data were analyzed with SAS 9.0 (SAS Institute, Cary, NC) and Epi Info 3.3.2 (CDC, Atlanta, GA) software. Estimates of incidence density rates and rate ratios were computed by using OpenEpi software (OpenEpi, Atlanta, Georgia). Survival analyses, including Cox proportional-hazard models, were conducted with SAS software. All significance tests were 2-tailed, and a P value of ≤.05 was considered statistically significant. Confounding by a variable was defined at the analytical stage if the adjusted incidence rate ratio derived from stratification of that variable differed from the crude rate ratio by ≥5%.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
During 1986 to 1998, 364 HIV-infected children were enrolled in PACTS (Table 1); 165 OIs occurred in 113 children (31%) during the entire period in which the study cohort was observed. One hundred fifty-three OIs occurred (in 1061 person-years of observation) during the pre-HAART era, and 12 OIs occurred (in 1101 person-years of observation) during the post-HAART era, which yielded an incidence rate ratio of 0.08 (95% confidence interval: 0.04–0.14). The outcome for each child enrolled depended on many dynamic exposure variables over the 18-year course of the study, including age, birth date, and length of exposure in defined time periods at high-risk ages (before HAART, before trimethoprim/sulfamethoxazole, and before intravenously administered immunoglobulin) (Fig 1).


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  		TABLE 1 Characteristics of HIV-Infected Children Who Developed OIs (N = 165) in the Pre-HAART Era (Before January 1, 1997) and the Post-HAART Era

 

Figure 1
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  		FIGURE 1 Relationship of birth and OI event distribution to potential effect-modifying exposures experienced by HIV-infected children enrolled in PACTS/PACTS-HOPE who developed OIs during the pre-HAART (before January 1, 1997) and post-HAART eras, showing that children born in an earlier chronological year had a longer average duration of follow-up monitoring and that most children were born in the pre-HAART era. Upper, Distributions of births (first row) and OI events (second row) among the study cohort according to calendar year. Lower, Potential life exposure to available interventions according to possible years of birth for children of varying age groups in the pre-HAART and post-HAART eras (first row) and exposure to HIV disease intervention milestones according to calendar year (second row). TMP/SMX indicates trimethoprim/sulfamethoxazole; NRTI, nucleoside reverse transcriptase inhibitor; AZT, zidovudine; AZT 076, zidovudine mother-to-child transmission prophylaxis; IVIG, intravenously administered immunoglobulin.

 
Incidence rates and the relative frequencies of specific OIs in each era are shown in (Table 2). Pneumocystis jiroveci pneumonia (PCP), RBIs, extraocular cytomegalovirus (CMV), and nontuberculous mycobacteria (NTM) (including Mycobacterium avium complex and Mycobacterium kansasii) were the most frequent OIs in the pre-HAART era, accounting for 37.3%, 29.4%, 9.8%, and 9.2% of OIs, respectively. In the post-HAART era, Candida esophagitis was the most frequent OI, accounting for 33.3% (compared with 6.5% in the pre-HAART era), with PCP (25%), RBIs (16.7%), NTM (16.7%), and extraocular CMV (9.1%) remaining the next most frequent OIs. Several OIs that had been relatively infrequent in the pre-HAART era (respiratory candidiasis, extrapulmonary cryptococcosis, cryptosporidiosis, CMV retinitis, herpes simplex virus infection, and extrapulmonary tuberculosis) had no cases in the post-HAART era. Statistically significant reductions in incidence were seen for PCP, RBIs, extraocular CMV, disseminated NTM, and respiratory candidiasis, whereas declines involving the remaining, less-frequent OIs did not achieve statistical significance (Table 2). When analysis was restricted to OIs that occurred at ≤6 years of age, there was a statistically significant decline in the incidence of Candida esophagitis (data not shown). Stated differently, in the pre-HAART era, all Candida esophagitis cases occurred in children ≤6 years of age; in the post-HAART era, 6 of 7 Candida esophagitis cases occurred in children >6 years of age. For PCP, RBIs, extraocular CMV, disseminated NTM, and respiratory candidiasis, the incidence rate ratio ranged from 0.0 to 0.14, indicating an 86%–100% reduction in the incidence of those OIs.


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  		TABLE 2 Incidence Rates of OIs According to Anatomic Sites Among HIV-Infected Children (N = 364) in the Pre-HAART Era (Before January 1, 1997) and the Post-HAART Era

 
Because most OIs occurred in children <6 years of age, the times from birth to the first OI for all children <6 years of age who were born before versus after January 1, 1997, were compared through Kaplan-Meier analysis (Fig 2). The results of this analysis illustrated dramatically more rapid acquisition of OIs by HIV-infected children born in the pre-HAART era, compared with those born later (P < .0001, log-rank test). Only 1 OI occurred in a child born in the post-HAART era.


Figure 2
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  		FIGURE 2 Kaplan-Meier analysis of time to development of the first OI in children ≤6 years of age, comparing children who were born before January 1, 1997 (pre-HAART era), with those born after January 1, 1997 (post-HAART era).

 
Age-related incidence rates were calculated for age strata of <6 years, on the basis of the same rationale already provided. In that age group, there were 107 first OI occurrences, yielding 103 and 4 first OIs in the pre-HAART and post-HAART eras, respectively. OI rates in the pre-HAART and post-HAART eras were 12.5 cases per 100 person-years and 0.8 cases per 100 person-years, respectively (Table 3). When the data were stratified according to age intervals of 2 years, OI incidence rates declined significantly in the 0- to 2-year and 2- to 4-year age strata, from the pre-HAART era to the post-HAART era. A similar trend was noted for the 4- to 6-year age stratum but failed to achieve statistical significance, probably because of the small number of events in those cells. Significant declines in OIs from the pre-HAART era to the post-HAART era were also noted in both gender and race groups.


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  		TABLE 3 Incidence Rates of First OIs Among HIV-Infected Children (N = 364) in the First 6 Years of Life in the Pre-HAART Era (Before January 1, 1997) and the Post-HAART Era

 
In the characterization of other mediating factors, such as immunologic status, that might have contributed to the decline in OI incidence, the method of Denny et al22 was adapted to analyze differences in the temporal trends of percentages of CD4+ cells and HIV RNA viral loads among patients who developed OIs, compared with those who never had an OI. Because the large majority of OIs occurred by 6 years of age, analyses were limited to percentage of CD4+ cells values from that age range and from several age strata within that range. At <3 years of age, children who never developed an OI experienced a decline in their percentage of CD4+ cells (r = –0.28; P < .001, Pearson's test), as did those who had ≥1 OI (r = –0.49; P < .001, Pearson's test); however, the rate of decline of percentage of CD4+ cells was slower in the former group (P = .02) (Fig 3). When all children <6 years of age were analyzed, there was no significant difference in the trends in percentages of CD4+ cells among children with and without OIs (P = .38). Similar analysis of the HIV RNA viral loads did not reveal any significant differences between trends (P > .05).


Figure 3
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  		FIGURE 3 Correlation of percentage of CD4+ cell trends among HIV-infected children <3 years of age, comparing children who experienced an OI (OI+) with those who never developed an OI (OI–).

 
Mortality rates among children with OIs were assessed through Kaplan-Meier analysis; results of this analysis revealed significantly higher mortality rate, with a shorter time to death, among children with OIs than among those without OIs (P < .0001, log-rank test) (Fig 4). With the Cox proportional-hazards model, the risk of death was higher among children with OIs (hazard ratio: 5.6; 95% confidence interval: 3.6–8.8), after adjustment for gender, race, and site of care.


Figure 4
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  		FIGURE 4 Kaplan-Meier analysis of deaths of HIV-infected children, comparing children who experienced an OI with those who never developed an OI.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
In this 18-year, multicenter, prospective cohort study, there were 86%–100% reductions in the incidence rates of PCP, RBIs, extraocular CMV, disseminated NTM, and respiratory candidiasis, in a comparison of the time periods before and after January 1, 1997 (the pre-HAART and post-HAART eras, respectively). Furthermore, there was a significant prolongation in the time to the development of a first OI among children born during the post-HAART era. We explored the basis for the declining incidences by comparing the trends in percentages of CD4+ cells during the first 3 years of life for children with and without OIs, and we found a more-marked decline in the percentage of CD4+ cells among children with a history of OIs. This trend was not found among those >3 years of age, likely because >80% (136 of 165) of all OIs occurred in children <3 years of age, and the median time to the first OI was 9.3 months. Not surprisingly, the occurrence of an OI was associated significantly with an increased mortality rate.

Among the strengths of this cohort were its follow-up period and its size. Between 1986 and 1998, >2000 mother-infant pairs were enrolled and 364 HIV-infected children were identified; with follow-up monitoring continuing into 2004, this cohort constitutes one of the largest of its kind in the world. For the study, we were able to ascertain clinical data comprehensively because (1) prenatal HIV testing was routine at participating institutions at an early time, (2) large proportions of the HIV-exposed mother-infant pairs were enrolled at the participating sites, (3) clinical care of the patients was performed by the study investigators, and (4) clinical diagnoses were recorded by study staff members at the time of diagnosis.

Although this study was prospective, one limitation is that it was not controlled and therefore was not designed to determine causal relationships between variables and outcomes. The duration of the study, spanning many of the management milestones of the HIV/AIDS epidemic, made analysis of the data very challenging. Primary prophylaxis of OIs,23,24 graduated antiretroviral therapy uptake (monotherapy then dual therapy then HAART), intravenously administered immunoglobulin prophylaxis of bacterial infections,25–27 monitoring of therapy with quantitative HIV RNA viral load determinations, routine voluntary HIV antibody testing for pregnant women,28 and antiretroviral prophylaxis of mother-to-child transmission29,30 are prime examples of these milestones. As a result of HIV testing and antiretroviral prophylaxis recommendations made in late 1994, the number of HIV-infected newborns decreased strikingly. After that time, there was an attendant decrease in the person-years of observation spent during the first 2 years of life, a time when the 2 most common OIs of HIV-infected children (PCP and RBIs) occur frequently. HIV-infected children in our cohort were born at varying times relative to the aforementioned milestones and thus differed greatly in the benefit they might have received from any particular innovation. These milestones are contextualized with the numbers of births and OIs per year, as well as with opportunity of an age group to spend person-time in any given period (Fig 1). Interestingly, the distribution of OIs followed closely the distribution of births, that is, the peak incidence of OIs was distributed temporally close to that of births, a relationship that contrasts with that for bacteremia, whose peak incidence lagged that of births by ~2 years (unpublished data, 2007).

Our method of analyzing OIs according to their occurrence in the pre-HAART and post-HAART eras acknowledges that not all HIV-infected children actually received HAART and not all HAART recipients began therapy at the same time. It is also noteworthy that, although we included multiple different OIs per patient in our analysis, we chose to include only first occurrences of any given OI. This is because there is little consensus regarding what length of time needs to elapse before an OI can be considered resolved and consequently when a patient's "at-risk" period for a true recurrence of that same OI returns. The alternative method would have been to calculate actual time spent receiving HAART per individual child and to count OIs as occurring in recipients or nonrecipients. This approach was not chosen because it would have been subject to the bias that "sicker" children were among the first to be placed on HAART; therefore, this method would likely have underestimated the benefit of HAART.

The OI incidence rates estimated in the present study are comparable to those reported in the few previous pediatric studies that addressed this topic. The Pediatric Spectrum of Disease (PSD) study investigators reported incidence rates for OIs in both the pre-HAART and post-HAART eras13; however, their findings showed post-HAART era OI incidence reductions in the range of 16%–56%, whereas our findings showed reductions between 86% and 100%. This percentage difference might have occurred because 45% of the 2148 children in the PSD cohort were enrolled through hospital-based surveillance, and 36% were >1 year of age.31 The Pediatric AIDS Clinical Trials Group (PACTG) has also reported on OI rates among children enrolled in antiretroviral protocols during the pre-HAART10 and post-HAART11,12 eras. Our pre-HAART data differ from those of these 2 studies in the incidence rate of the most common OI, PCP. In PACTS, the incidence of PCP in the pre-HAART era was >4 times the rate in the PACTG study13 and almost 2 times that in the PSD study.10 This difference is likely attributable to our cohort's uniqueness in having captured the window of greatest risk for PCP (6 weeks to 1 year), whereas the median ages of all children enrolled in the various PACTG protocols and the PSD study were substantially older. As in the PACTG studies,11,12 we counted only first-time OIs. Our post-HAART data and those of the PACTG study11 show similar OI incidence rates, with the exception again being PCP (0.09 cases per 100 patient-years in the PACTG study and 0.3 cases per 100 patient-years in PACTS).


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
In our cohort, declining incidence rates were seen for all OIs. In some cases, the low frequency of certain OIs did not allow declining trends to achieve statistical significance, although all of these OIs seemed to decrease. These changes are attributable largely to the widespread use of HAART but also to improvements in care, such as improved identification of at-risk infants (through testing of pregnant women) and improved use of OI prophylaxis. Parallel to improvements in care has been the remarkable decrease in mother-to-child HIV transmission. The unique aspects of this long-term study allowed us to measure and to contextualize these changes. It remains to be seen whether these declining trends in OI incidence will be sustained as more children proceed through adolescence and whether a similar pattern of decline in OI incidence will be seen as HAART becomes more available to resource-poor areas.


   ACKNOWLEDGMENTS
 
PACTS and PACTS-HOPE were funded by the CDC through cooperative agreements U64/CCU207228 (Medical and Health Research Association of New York City), U64/CCU202219 (University of Medicine and Dentistry of New Jersey, New Jersey Medical School), U64/CCU306825 (University of Maryland School of Medicine), and U64/CCU404456 (Emory University School of Medicine).

At Emory University, Vickie Grimes served as research nurse for the duration of the study, and her work is greatly appreciated. At the University of Maryland, Drs Peter Vink and Vicki Tepper served as site principal investigators, Sue Hines as study coordinator, and Katie Peery as research assistant. At the University of Medicine and Dentistry of New Jersey, Linda Bettica, RN, served as research coordinator and Jeffrey Swerdlow as database manager. We also thank the participants in the New York City PACTS Group, as follows: Bronx Lebanon Hospital, Saroj Bakshi, Genevieve Lambert, Elizabeth Adams, and Delia Grant; Harlem Hospital Center, Susan Champion, Julia Floyd, Cynthia Freeland, Margaret Heagarty, Pamela Prince, Desiree Minnott, and Aretha Bellmore; Jacobi Hospital Center, Joanna Dobroszycki, Adell Harris, and Andrew Wiznia; Metropolitan Hospital Center, Mahrukh Bamji, Grace Canillas, Lynn Jackson, and Nancy Cruz; Medical and Health Research Association of New York City, Tina Alford, Rosalind Carter, Mary Ann Chiasson, Eileen Rillamas-Sun, Donald Thea, and Jeremy Weedon; Montefiore Medical Center, Ellie Schoenbaum and Marcelle Naccarato. Finally, at the CDC, the following staff members contributed substantially to PACTS: Martha Rogers, Nathan Shaffer, Rick Steketee, and RJ Simonds; to PACTS-HOPE: Darcy Freedman, Jeff Wiener, Bob Yang, and April Bell.


   FOOTNOTES
 
Accepted Mar 7, 2007.

Address correspondence to Bill G. Kapogiannis, MD, Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, 6100 Executive Blvd, Room 4B11J, Bethesda, MD 20892-7510. E-mail: kapogiannisb{at}mail.nih.gov

The authors have indicated they have no financial relationships relevant to this article to disclose. Dr Kapogiannis’ current affiliation is Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. Dr Bulterys’ current affiliation is CDC Global AIDS Program, Lusaka, Zambia.

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics




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