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ABSTRACT: OBJECTIVE: The greater New York metropolitan area includes 8 medical schools. Their alumni association (AA) presidents formed a council 6 years ago, meeting 3 times a year to share ideas and identify best practices to solve mutual problems challenging students and alumni. METHODS: A survey of the 8 medical AAs was conducted; all responded, and the results constitute the data in this report. RESULTS: Mean AA membership was 2509 or 33% of mean alumni populations (7489). Two AAs conferred membership at graduation; hence, 100% of alumni were AA members. Omitting these 2 AAs reduced mean participation to 1722 or 23%. Alumni association support staff averaged 3.8 persons (range, 1-7 persons). The 2 most frequently cited AA challenges were membership and fund-raising. All AAs had annual or biennial reunions and considered the reunion to be a major commitment of resources. Despite this commitment, mean reunion attendance was only 242 alumni (range, 40-500 alumni) or 7.3% of alumni in anniversary years (5-year intervals). The mean number of alumni who contributed annually to their alma mater through its AA was 1936 alumni (range, 500-3500 alumni), or 26% (range, 5%-47%). Medical AAs reported mean assets of $2,755,000 (range, $6475-$11,000,000). The mean AA budget was $298,750, of which 65% (range, 13%-100%) was devoted to "medical student support". The most frequently cited student activities were "career night" (100%), "white coat ceremonies" (63%), medical equipment (stethoscopes, etc, 50%), and alumni host programs (38%). Eleven additional medical student activities received financial support from the 8 AAs in varying proportions. CONCLUSIONS: Each AA in the Greater Metropolitan Medical Alumni Council has derived significant benefit from the application of best practices to its individual problem set. In particular, a nascent AA developed significant momentum in its formation and development by its participation in the Greater Metropolitan Medical Alumni Council. Additionally, these data provide a foundation for the development of best practices within medical school AA for optimizing support of student programs and alumni participation. Stronger AAs will translate into enhanced support of educational programs for medical students. We urge formation of similar medical AA organizations in other metropolitan areas.
Journal of Investigative Medicine 06/2013; · 1.96 Impact Factor
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ABSTRACT: OBJECTIVE:: Previous studies of cardiomyopathy among children perinatally infected with HIV were conducted before the routine use of HAART. Nucleoside analogs [nucleoside reverse transcriptase inhibitors (NRTIs)], the backbone of HAART, have been associated with mitochondrial toxicity, which can lead to cardiomyopathy. We evaluated the association of HAART and specific NRTIs associated with mitochondrial toxicity, on development of cardiomyopathy among perinatally HIV-infected children. DESIGN:: Three thousand and thirty-five perinatally HIV-infected children enrolled in a US-based multicenter prospective cohort study were followed for cardiomyopathy, defined as a clinical diagnosis or initiation of digoxin, from 1993 to 2007. METHODS:: Cox models were used to estimate the effects of HAART and NRTIs on cardiomyopathy, identify predictors of cardiomyopathy among HAART users, and estimate the association between development of cardiomyopathy and mortality. RESULTS:: Ninety-nine cases of cardiomyopathy were identified over follow-up (incidence rate: 5.6 cases per 1000 person-years) at a median age of 9.4 years. HAART was associated with a 50% lower incidence of cardiomyopathy compared with no HAART use (95% confidence interval: 20%, 70%). Zalcitabine (ddC) use, however, was associated with an 80% higher incidence of cardiomyopathy. Among HAART users, older age at HAART initiation, ddC use before HAART initiation, initiating a HAART regimen containing zidovudine (ZDV), and a nadir CD4 percentage less than 15% were independently associated with a higher rate of cardiomyopathy. Cardiomyopathy was associated with a six-fold higher mortality rate. CONCLUSION:: HAART has dramatically decreased the incidence of cardiomyopathy among perinatally HIV-infected children. However, they remain at increased risk for cardiomyopathy and ongoing ZDV exposure may increase this risk.
AIDS (London, England) 07/2012; 26(16):2027-2037. · 4.91 Impact Factor
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ABSTRACT: PURPOSE: Perinatally HIV-infected children, who are increasingly aging into adolescence and early adulthood, have significant rates of psychiatric co-morbidities, some of which are treated with second-generation antipsychotics (SGAs). SGAs have been associated with elevated total cholesterol (TC) in youth, but no studies have examined this association in perinatally HIV-infected youth. This study examined changes in TC levels of youth with perinatally acquired HIV infection and co-morbid psychiatric conditions treated with SGAs. PATIENTS AND METHODS: Long-term changes in TC levels were examined using data from the US multisite prospective Pediatric AIDS Clinical Trials Group 219C cohort study. The change in TC levels from baseline to 12 months after initiating SGA use was compared between 52 SGA-exposed and 148 matched SGA-unexposed perinatally HIV-infected youth, using generalized estimating equation models adjusting for other covariates. The prevalence and time to incident hypercholesterolemia were also compared between these 2 groups. RESULTS: After adjustment for confounders, 52 youth with prescriptions for SGAs had a larger increase in TC levels than 148 matched youth without antipsychotic prescriptions (mean difference = 9 mg/dL, z = 1.96, df = 1, P = 0.0496). Among youth with TC below 220 mg/dL at baseline, 27% of SGA-exposed youth developed hypercholesterolemia (defined as two consecutive TC measurements ≥220 mg/dL), compared with 13% of SGA-unexposed patients (Fisher's exact test, P = 0.046). CONCLUSIONS: Caution should be used in prescribing SGAs to perinatally HIV-infected youth with psychiatric co-morbidities due to increased risk of hypercholesterolemia. Patients should be monitored, and alternative evidence-based treatments considered when available.
Neurobehavioral HIV Medicine 08/2010; 2010(2):39-48.
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Marilyn J Crain,
Miriam C Chernoff, James M Oleske,
Susan B Brogly,
Kathleen M Malee,
Peggy R Borum,
William A Meyer,
Wendy G Mitchell,
John H Moye,
Heather M Ford-Chatterton,
Russell B Van Dyke,
George R Seage Iii
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ABSTRACT: Mitochondrial dysfunction has been associated with both human immunodeficiency virus (HIV) infection and exposure to antiretroviral therapy. Mitochondrial dysfunction has not been widely studied in HIV-infected children. We estimated the incidence of clinically defined mitochondrial dysfunction among children with perinatal HIV infection.
Children with perinatal HIV infection enrolled in a prospective cohort study (Pediatric AIDS Clinical Trials Group protocols 219 and 219C) from 1993 through 2004 were included. Two clinical case definitions of mitochondrial dysfunction, the Enquête Périnatale Française criteria and the Mitochondrial Disease Classification criteria, were used to classify signs and symptoms that were consistent with possible mitochondrial dysfunction. Adjusted odds ratios of the associations between single and dual nucleoside reverse-transcriptase inhibitor use and possible mitochondrial dysfunction were estimated using logistic regression.
Overall, 982 (33.5%) of 2931 children met 1 or both case definitions of possible mitochondrial dysfunction. Mortality was highest among the 96 children who met both case definitions (20%). After adjusting for confounders, there was a higher risk of possible mitochondrial dysfunction among children who received stavudine regardless of exposure to other medications (odds ratio, 3.44 [95% confidence interval, 1.91-6.20]) or who received stavudine-didanosine combination therapy (odds ratio, 2.23 [95% confidence interval, 1.19-4.21]). Exposure to lamivudine and to lamivudine-stavudine were also associated with an increased risk of mitochondrial dysfunction.
Receipt of nucleoside reverse-transcriptase inhibitors, especially stavudine and lamivudine, was associated with possible mitochondrial dysfunction in children with perinatal HIV infection. Further studies are warranted to elucidate potential mechanisms of nucleoside reverse-transcriptase inhibitor toxicities.
The Journal of Infectious Diseases 07/2010; 202(2):291-301. · 6.41 Impact Factor
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ABSTRACT: Introduction of highly active antiretroviral therapy has significantly decreased mortality in HIV-1-infected adults and children. Although an increase in non-HIV-related mortality has been noted in adults, data in children are limited.
To evaluate changes in causes and risk factors for death among HIV-1-infected children in Pediatric AIDS Clinical Trials Group 219/219C.
Multicenter, prospective cohort study designed to evaluate long-term outcomes in HIV-1-exposed and infected US children. There were 3553 HIV-1-infected children enrolled and followed up between April 1993 and December 2006, with primary cause of mortality identified in the 298 observed deaths.
Mortality rates per 100 child-years overall and by demographic factors; survival estimates by birth cohort; and hazard ratios for mortality by various demographic, health, and antiretroviral treatment factors were determined.
Among 3553 HIV-1-infected children followed up for a median of 5.3 years, 298 deaths occurred. Death rates significantly decreased between 1994 and 2000, from 7.2 to 0.8 per 100 person-years, and remained relatively stable through 2006. After adjustment for other covariates, increased risk of death was identified for those with low CD4 and AIDS-defining illness at entry. Decreased risks of mortality were identified for later birth cohorts, and for time-dependent initiation of highly active antiretroviral therapy (hazard ratio 0.54, P < 0.001). The most common causes of death were "End-stage AIDS" (N = 48, 16%) and pneumonia (N = 41, 14%). The proportion of deaths due to opportunistic infections (OIs) declined from 37% in 1994-1996 to 24% after 2000. All OI mortality declined during the study period. However, a greater decline was noted for deaths due to Mycobacterium avium complex and cryptosporidium. Deaths from "End-stage AIDS," sepsis and renal failure increased.
Overall death rates declined from 1993 to 2000 but have since stabilized at rates about 30 times higher than for the general US pediatric population. Deaths due to OIs have declined, but non-AIDS-defining infections and multiorgan failure remain major causes of mortality in HIV-1-infected children.
JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2010; 53(1):86-94. · 4.43 Impact Factor
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Patricia A Sirois,
Grace Montepiedra,
Suad Kapetanovic,
Paige L Williams,
Deborah A Pearson,
Kathleen Malee,
Patricia A Garvie,
Betsy L Kammerer,
Sharon L Nichols,
Molly L Nozyce,
Mark Mintz,
Wendy G Mitchell, James M Oleske
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ABSTRACT: To examine the relationships between physical growth and medications prescribed for symptoms of attention-deficit hyperactivity disorder in children with HIV.
Analysis of data from children with perinatally acquired HIV (N = 2251; age 3-19 years), with and without prescriptions for stimulant and nonstimulant medications used to treat attention-deficit hyperactivity disorder, in a long-term observational study. Height and weight measurements were transformed to z scores and compared across medication groups. Changes in z scores during a 2-year interval were compared using multiple linear regression models adjusting for selected covariates.
Participants with (n = 215) and without (n = 2036) prescriptions were shorter than expected based on US age and gender norms (p < .001). Children without prescriptions weighed less at baseline than children in the general population (p < .001) but gained height and weight at a faster rate (p < .001). Children prescribed stimulants were similar to population norms in baseline weight; their height and weight growth velocities were comparable with the general population and children without prescriptions (for weight, p = .511 and .100, respectively). Children prescribed nonstimulants had the lowest baseline height but were similar to population norms in baseline weight. Their height and weight growth velocities were comparable with the general population but significantly slower than children without prescriptions (p = .01 and .02, respectively).
The use of stimulants to treat symptoms of attention-deficit hyperactivity disorder does not significantly exacerbate the potential for growth delay in children with HIV and may afford opportunities for interventions that promote physical growth. Prospective studies are needed to confirm these findings.
Journal of developmental and behavioral pediatrics: JDBP 10/2009; 30(5):403-12. · 2.27 Impact Factor
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Suad Kapetanovic,
Lisa Aaron,
Grace Montepiedra,
Patricia A Sirois, James M Oleske,
Kathleen Malee,
Deborah A Pearson,
Sharon L Nichols,
Patricia A Garvie,
John Farley,
Molly L Nozyce,
Mark Mintz,
Paige L Williams
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ABSTRACT: Second-generation antipsychotics (SGAs) are increasingly prescribed to treat psychiatric symptoms in pediatric patients infected with HIV. We examined the relationship between prescribed SGAs and physical growth in a cohort of youth with perinatally acquired HIV-1 infection. Pediatric AIDS Clinical Trials Group (PACTG), Protocol 219C (P219C), a multicenter, longitudinal observational study of children and adolescents perinatally exposed to HIV, was conducted from September 2000 until May 2007. The analysis included P219C participants who were perinatally HIV-infected, 3-18 years old, prescribed first SGA for at least 1 month, and had available baseline data prior to starting first SGA. Each participant prescribed an SGA was matched (based on gender, age, Tanner stage, baseline body mass index [BMI] z score) with 1-3 controls without antipsychotic prescriptions. The main outcomes were short-term (approximately 6 months) and long-term (approximately 2 years) changes in BMI z scores from baseline. There were 236 participants in the short-term and 198 in the long-term analysis. In linear regression models, youth with SGA prescriptions had increased BMI z scores relative to youth without antipsychotic prescriptions, for all SGAs (short-term increase = 0.192, p = 0.003; long-term increase = 0.350, p < 0.001), and for risperidone alone (short-term = 0.239, p = 0.002; long-term = 0.360, p = 0.001). Participants receiving both protease inhibitors (PIs) and SGAs showed especially large increases. These findings suggest that growth should be carefully monitored in youth with perinatally acquired HIV who are prescribed SGAs. Future research should investigate the interaction between PIs and SGAs in children and adolescents with perinatally acquired HIV infection.
AIDS patient care and STDs 10/2009; 23(11):939-47. · 2.68 Impact Factor
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ABSTRACT: The frequency of do-not-resuscitate (DNR) orders and hospice enrollment in children/adolescents living with acquired immune deficiency syndrome (AIDS) and followed in Pediatric AIDS Clinical Trials Group (PACTG) Study 219C was examined, and evaluated for any association with racial disparities or enhanced quality of life (QOL), particularly psychological adjustment.
A cross-sectional analysis of children with AIDS enrolled in this prospective multicenter observational study between 2000 and 2005 was conducted to evaluate the incidence of DNR/hospice overall and by calendar time. Linear regression models were used to compare caregivers' reported QOL scores within 6 domains between those with and without DNR/hospice care, adjusting for confounders.
Seven hundred twenty-six (726) children with AIDS had a mean age of 12.9 years (standard deviation [SD]=4.5), 51% were male, 60% black, 25% Hispanic. Twenty-one (2.9%) had either a DNR order (n=16), hospice enrollment (n=7), or both (n=2). Of 41 children who died, 80% had no DNR/hospice care. Increased odds of DNR/hospice were observed for those with CD4% less than 15%, no current antiretroviral use, and prior hospitalization. No differences by race were detected. Adjusted mean QOL scores were significantly lower for those with DNR/hospice enrollment than those without across all domains except for psychological status and health care utilization. Poorer psychological status correlated with higher symptom distress, but not with DNR/hospice enrollment after adjusting for symptoms.
Children who died of AIDS rarely had DNR/hospice enrollment. National guidelines recommend that quality palliative care be integrated routinely with HIV care. Further research is needed to explore the barriers to palliative care and advance care planning in this population.
Journal of Palliative Medicine 05/2008; 11(3):459-69. · 1.85 Impact Factor
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Vaccine 09/2007; 25(31):5754-62. · 3.77 Impact Factor
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James F Jones,
Katrin S Kohl,
Nooshin Ahmadipour,
Gijs Bleijenberg,
Dedra Buchwald,
Birgitta Evengard,
Leonard A Jason,
Nancy G Klimas,
Andrew Lloyd,
Kimberly McCleary, James M Oleske,
Peter D White
Vaccine 08/2007; 25(31):5685-96. · 3.77 Impact Factor
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ABSTRACT: The pathogenesis of HIV infection and the general principles of therapy are the same for HIV-infected adults, adolescents, children and infants. However, antiretroviral treatment of HIV infection in pediatrics requires the consideration of a number of factors specific to its population, including differences in drug pharmacokinetics and the use of virologic and immunologic markers, as well as age-related adherence issues. This review summarizes the text of the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, which was updated in October 2006. The guidelines are the work of the Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, a group of the Office of AIDS Research Advisory Council of the National Institutes of Health, which reviews new data on an ongoing basis and provides regular updates to the guidelines. As these guidelines were developed for the US, they may not be applicable in other countries. This summary does not attempt to place the Working Group guidelines in the context of international guidelines, nor does it attempt to detail the use of antiretroviral medication in the prevention of perinatal transmission of HIV, such as addressing the use of zidovudine versus single-dose nevirapine.
Expert Opinion on Pharmacotherapy 03/2007; 8(2):155-66. · 3.20 Impact Factor
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ABSTRACT: The addition of highly active antiretroviral therapy to the complex regimens used to treat HIV-infected persons has extended the lives of millions. Despite the proven benefits of antiretroviral therapy, adverse events can occur with its use. These reactions can be separated into several distinct categories: mitochondrial dysfunction, metabolic abnormalities, hematologic complications, and allergic reactions. Drug-associated complications can be particularly challenging to treat when they occur in pediatric HIV patients. Care providers who manage HIV-infected children have to be cognizant of these complications when patients present with symptoms because some can mimic manifestations of HIV infection itself. These adverse reactions are neither uncommon nor unexpected, and discontinuation of the inciting agent is not always mandated. But every effort must be made to address them when they do occur so that adequate treatment is given in a timely manner.
The AIDS reader 11/2006; 16(10):537-40, 544-6,549-50, 552-4. · 0.61 Impact Factor
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ABSTRACT: To assess sexual knowledge, behaviors, and procreational intentions of adolescents and young adults with perinatally acquired human immunodeficiency virus (PNA HIV) infection. Increasingly, children with PNA HIV infection survive to adolescence and become sexually active. Understanding their procreational intentions could aid in designing reproductive health and secondary prevention programs.
A cross-sectional survey of adolescents and young adults with PNA HIV infection at an urban tertiary center was conducted. From June 2003 through September 2004, participants completed a questionnaire that inquired about their sexual knowledge and behaviors. Participants aware of their diagnoses also completed items regarding procreational intentions.
Seventy-four percent (57/77) of eligible participants completed the survey. Thirty-three percent (19/57) of participants reported having had penile-vaginal intercourse, 89.4% of them after learning of their HIV status. Fifty percent (5/10) of sexually active female participants had been pregnant. Among the 50 participants who were aware of their diagnosis, 70% (n = 35) expressed intent to have children. A majority of those aware of the risk of maternal-to-child transmission (MTCT) (71.1%) expressed intent to procreate. Participants who perceived MTCT as low were more likely to express intent to procreate than those who perceived the risk of MTCT as high.
Adolescents with PNA HIV infection are becoming sexually active and express intent to have children. This has important implications for secondary prevention of HIV infection. These adolescents need innovative intervention programs offering reproductive health education including procreational choices and considerations.
Journal of Adolescent Health 07/2006; 38(6):719-25. · 3.33 Impact Factor
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ABSTRACT: 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.
To compare QoL among HIV-infected and uninfected children and to assess the impact of different antiretroviral regimens on QoL among HIV-infected children.
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.
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 (5-11 years of age) and adolescents (12-21 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.
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.
PEDIATRICS 03/2006; 117(2):273-83. · 4.47 Impact Factor
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ABSTRACT: 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.
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.
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.
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).
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).
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 identified.
JAMA The Journal of the American Medical Association 06/2005; 293(18):2213-20. · 30.03 Impact Factor
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Susan Schuval,
Jane C Lindsey,
Jack T Stapleton,
Russell B Van Dyke,
Paul Palumbo,
Lynne M Mofenson, James M Oleske,
Joseph Cervia,
Andrea Kovacs,
Wayne N Dankner, [......],
Gregory Ciupak,
Nancy Webb,
Michelle Eagle,
Dorothy Smith,
Roslyn Hennessey,
Melissa Goodman-Kerkau,
Donna Klinzman,
Georg Hess,
Dietmar Zdunek,
Myron J Levin
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ABSTRACT: GB virus C (GBV-C) infection occurs in 20-40% of human immunodeficiency virus (HIV)-infected adults, and coinfection is associated with improved HIV disease outcome.
To determine the prevalence of GBV-C infection in children who were perinatally infected with HIV, we conducted a cross-sectional prevalence survey in a cohort of perinatally infected HIV-positive children selected from a large, multicenter observational protocol. A blood specimen was obtained and tested for GBV-C viremia with the use of a qualitative GBV-C RNA assay and screened for past GBV-C infection with enzyme-linked immunosorbent assay to detect antibodies to the GBV-C envelope protein E2 (E2 Ab).
The 354 children who participated in the substudy were relatively healthy, with a median CD4 of 784 cells/mm and median HIV-1 viral load of 1055 copies/mL. The prevalence of GBV-C viremia was 20 of 353 or 5.7% (95% confidence interval, 3.5-8.6%), and the prevalence of E2 Ab was 12 of 354 or 3.4% (95% confidence interval, 1.8-5.8%). GBV-C viremic patients were older than patients without past GBV-C infection (median age, 12.8 years versus 10.7 years). Median CD4 lymphocyte counts were highest in subjects without GBV-C infection and lowest in those with E2 Ab.
GBV-C prevalence rates are lower in children with perinatal HIV infection than those reported for HIV-infected adults. With the exception of evidence that GBV-C viremic children had lower rates of Centers for Disease Control and Prevention HIV disease category C disease before GBV-C testing, we did not find evidence of improved HIV disease outcome in coinfected patients, but the number of HIV/GBV-C-coinfected children was small.
The Pediatric Infectious Disease Journal 06/2005; 24(5):417-22. · 3.58 Impact Factor
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ABSTRACT: This study examines quality of life (QOL) among school-aged children with perinatally acquired HIV infection and compares QOL outcomes between treatment groups that differ according to the use of protease inhibitor (PI) combination therapy (PI therapy). To gain insights into how PI therapy might influence QOL, associations between severity of illness and QOL were also investigated.
Cross-sectional data for 940 children, 5 to 18 years of age, who were enrolled in Pediatric AIDS Clinical Trials Group Late Outcomes Protocol 219 were used to examine domains of caregiver-reported QOL, as assessed with the General Health Assessment for Children, during 1999. The General Health Assessment for Children is an age-specific, modular, QOL assessment that was developed for the study with previously validated measures. QOL differences between treatment groups were estimated with linear and logistic regressions that controlled for sociodemographic characteristics (age, gender, race/ethnicity, maternal/caregiver education, and respondent) and severity-of-illness indicators related to receipt of PI therapy (AIDS status, log(10) CD4+ cell counts, and height-for-age z scores).
The mean age of participants was 9.7 years. Most children were non-Hispanic black (54%) or Hispanic (31%), and 49% of the participants were female. At the 1999 study visit, approximately 14% of children had severe immune suppression (<15% CD4+ cells), whereas 62% of children had > or =25% CD4+ cells, ie, no immune suppression. Participants did exhibit some lag in growth, with mean height and weight z scores of -0.70 and -0.20, respectively. Twenty-eight percent of the children were reported to have met criteria for AIDS at study entry (1993-1999). When treatment groups were compared, children receiving PI therapy (72%) were older, had lower CD4+ cell percentages, and had lower height and weight z scores than did those receiving non-PI therapies. They were also more likely to have met criteria for AIDS at study entry. The most commonly used PIs were ritonavir (46%) and nelfinavir (63%). Health perceptions ratings for most children were at the upper end of the scale, whereas ratings for 25% of the children ranged over the lower 70% of scale scores. Almost one half of the children had at least some limitations in physical functioning, with more frequent limitations in energy-demanding activities (46%) than in basic activities of daily living (32%). The Behavior Problems Index was used to assess psychologic functioning. The mean total Behavior Problems Index score (9.34) and the proportion of children with extreme scores (23%) were consistent with values reported for chronically ill children and those at social and economic risk. One or more limitations in social/school functioning were reported for 58% of children. More than one third of the children (38%) experienced > or =1 physical symptoms that were at least moderately distressing. Health perceptions, physical functioning, psychologic functioning, social/school functioning, and overall HIV symptom scores did not differ between treatment groups. However, receipt of PI therapy was associated with an increased rate of diarrhea (28 vs 13%; adjusted odds ratio: 2.59; 95% confidence interval: 1.74-3.85). Severity of illness was associated with QOL in all domains except psychologic functioning. Higher log(10) CD4+ cell counts, higher height-for-age z scores, and absence of AIDS at study entry were independently associated with fewer social/school limitations and better HIV symptom scores. Health perceptions and physical functioning scores were associated with log(10) CD4+ cell counts and height z scores, respectively.
QOL among children receiving PI therapy differed little from that among children receiving non-PI therapy, despite clinical indications of more advanced disease. Importantly, the study found no evidence of direct negative effects of PI therapy on QOL outcomes, other than an increased rate of diarrhea. Findings suggest that the effects of PI combination therapies to slow or to prevent disease progression and to increase CD4+ cell counts and height growth have the potential to improve QOL among children with HIV infection. However, many children do experience a constellation of functional impairments indicated by behavioral problems and clinical symptoms, with limitations in activities and in school performance. Comprehensive health services will continue to be required to minimize long-term illness and disability and to maximize children's potential as they move into adolescence and adulthood.
PEDIATRICS 02/2005; 115(2):e173-82. · 4.47 Impact Factor
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Susan Schuval,
Russell B Van Dyke,
Jane C Lindsey,
Paul Palumbo,
Lynne M Mofenson, James M Oleske,
Joseph Cervia,
Andrea Kovacs,
Wayne N Dankner,
Elizabeth Smith,
Barbara Nowak,
Gregory Ciupak,
Nancy Webb,
Michelle Eagle,
Dorothy Smith,
Roslyn Hennessey,
Melissa Goodman-Kerkau,
Myron J Levin
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ABSTRACT: To evaluate the prevalence of hepatitis C virus (HCV) infection in children with perinatal human immunodeficiency virus (HIV) infection.
Cross-sectional substudy.
Multicenter study from 41 sites in the United States.
Children with perinatal HIV infection were randomly selected from a large, long-term, follow-up protocol.
Hepatitis C infection was defined as having positive test results on both HCV antibody and HCV RNA assays.
Five hundred thirty children enrolled in the substudy; definitive HCV test results were available for 525 children. Eighty-three percent were of a minority race or ethnicity. They were equally distributed by sex, had a median age of 10.7 years, and were relatively healthy, with 75% having CD4+ lymphocyte counts greater than 500 cells/mm3. Eight of 525 children (1.5%; 95% confidence interval [CI], 0.7%-3.0%) infected with HIV were coinfected with HCV. In contrast, the rate of HCV infection in a serosurvey of more than 2700 children aged 6 to 11 years from the National Health and Nutrition Examination Survey was 0.2% (95% CI, 0.04%-0.6%). In our study, there were no differences between children coinfected with HIV and HCV and those without HCV infection in terms of demographic characteristics, CD4+ or CD8+ T-lymphocyte counts, HIV 1 RNA levels, preterm or mode of delivery, or liver disease; however, the number of children coinfected with HIV and HCV was small.
While HCV prevalence infection rates are low in children with perinatal HIV infection, they are 8 to 10 times higher than reported in HCV serosurveys of children in the United States.
Archives of Pediatrics and Adolescent Medicine 11/2004; 158(10):1007-13. · 4.14 Impact Factor
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ABSTRACT: Psychiatric manifestations of pediatric human immunodeficiency virus (HIV) infection have been described. However, data on severe sequelae requiring hospitalization among this population have not been reported.
The Pediatric Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group (PACTG) 219C is a prospective cohort study designed to examine long-term outcomes among HIV-infected children and HIV-uninfected infants born to HIV-infected women. Children with HIV infection who have enrolled in PACTG 219C are examined quarterly, with collection of clinical and laboratory data. Hospitalizations and diagnoses for all participants between September 2000 (when enrollment into PACTG 219C was started) and December 2002 were reviewed.
Among 1808 HIV-infected participants who were <15 years of age at the last visit date, 25 children had been hospitalized for psychiatric manifestations, 8 before enrollment into PACTG 219C. Seventeen children were hospitalized during 2757 person-years of follow-up monitoring after entry into PACTG 219C, which represents an incidence of 6.17 cases per 1000 person-years (95% confidence interval: 3.59-9.87 cases per 1000 person-years). This was significantly higher than the incidence of 1.70 cases per 1000 person-years (95% confidence interval: 1.67-1.72 cases per 1000 person-years) in the general pediatric population <15 years of age, as reported in the 2000 National Hospital Discharge Survey, yielding a relative rate of 3.62 (95% confidence interval: 2.11-5.80). A total of 32 HIV-infected children, regardless of age, were hospitalized because of psychiatric illnesses. The majority of patients were admitted because of depression (n = 16) or behavioral disorders (n = 8). Fifteen (47%) underwent multiple psychiatric hospitalizations. The median age at the first psychiatric hospitalization was 11 years (range: 4-17 years); all patients had been perinatally infected. Knowledge of HIV seropositivity status and having experienced a significant life event were both significantly associated with an increased risk of psychiatric hospitalization (hazard ratios of 6.13 and 3.04, respectively). No psychiatric hospitalizations were observed among the 1021 HIV-uninfected members of the cohort.
Children with HIV/AIDS are at increased risk for psychiatric hospitalizations during childhood and early adolescence, compared with the general pediatric population. Knowledge of HIV seropositivity status and recent significant life events were significantly associated with increased risks of admission in this population.
PEDIATRICS 06/2004; 113(6):e544-51. · 4.47 Impact Factor
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Chang-Heok Soh, James M Oleske,
Michael T Brady,
Stephen A Spector,
William Borkowsky,
Sandra K Burchett,
Marc D Foca,
Edward Handelsman,
Eleanor Jiménez,
Wayne M Dankner,
Michael D Hughes
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ABSTRACT: There is limited evidence about longer-term effects of combination antiretroviral therapy that includes protease inhibitors (PIs) on the immunological status of HIV-1-infected children. Better understanding might help to resolve questions on when to initiate treatment.
The change in percentage of CD4-positive T lymphocytes (CD4%) was investigated in 1012 previously treated HIV-1-infected children (aged 0-17 years) who were enrolled in research clinics in the USA before 1996 and followed up to 2000. 702 started PI-based combination therapy. Data analyses ignored subsequent treatment changes.
Among the 1012 children, the median CD4% increased from 22% to 28% between 1996, when PIs were first prescribed, and 2000. For the 702 who started PI-based therapy, the mean CD4% increase after 3 years was largest among participants with the greatest immunosuppression (15.7%, 10.6%, 5.1%, and 2.0% for participants with CD4% before therapy of <5%, 5-14%, 15-24%, and >25%; p<0.0001). After adjustment for pre-PI CD4%, the mean increase was largest among the youngest participants (9.2%, 8.0%, and 4.3% for ages <5 years, 5-9 years, and >10 years; p=0.001). However, only a minority of significantly immunocompromised participants (33%, 26%, and 49% of those with pre-PI CD4% of <5%, 5-14%, or 15-24%) achieved CD4% values above 25%, whereas 84% of those with pre-PI values above 25% maintained such values.
Although PI-based therapy was associated with substantial improvements in CD4%, initiation before severe immunosuppression and at younger ages may be more effective for recovery or maintenance of normal CD4%. Randomised investigation of when to start combination therapy in children, particularly infants, is needed.
The Lancet 12/2003; 362(9401):2045-51. · 38.28 Impact Factor
