Heidi Schwarzwald

Lipodystrophy syndrome in human immunodeficiency virus-infected children.

Background. Lipodystrophy syndrome in HIV-infected adults is characterized by a variety of physical and/or metabolic abnormalities, including fat redistribution, hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia) and peripheral insulin resistance. Many studies suggest that antiretroviral therapy is the underlying cause of the condition. Few data exist for HIV-infected children. Methods. This is a cross-sectional study evaluating HIV-infected children age 2 to 16 years. Fat redistribution was identified by physical examination and parental questionnaire. Fasting blood analysis included cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, glucose, insulin and C-peptide. Results. Forty HIV-infected children were recruited. Seven children (18%) exhibited physical signs of fat redistribution. Twenty-seven (68%), 11 (28%) and 3 (8%) children exhibited evidence for hypercholesterolemia, hypertriglyceridemia and insulin resistance, respectively. Eleven children (28%) had no physical signs or laboratory evidence of lipodystrophy. Statistical analysis did not reveal any significant association between the presence of lipodystrophic features and patient age, HIV-1 viral load, exposure to specific antiretroviral medications or duration of protease inhibitor or nucleoside reverse transcriptase inhibitor therapy. Drug dosing was significantly associated with the development of lipodystrophy features. Children receiving pediatric dosing regimens vs. adult dosing regimens were less likely to develop lipodystrophy (P = 0.003). Conclusions. Features associated with lipodystrophy syndrome arise in some HIV-infected children. Subjects receiving pediatric dosing regimens were less likely than those receiving adult regimens to develop lipodystrophy.

Transitioning HIV-Infected Youth Into Adult Health Care

With advances in antiretroviral therapy, most HIV-infected children survive into adulthood. Optimal health care for these youth includes a formal plan for the transition of care from primary and/or subspecialty pediatric/adolescent/family medicine health care providers (medical home) to adult health care provider(s). Successful transition involves the early engagement and participation of the youth and his or her family with the pediatric medical home and adult health care teams in developing a formal plan. Referring providers should have a written policy for the transfer of HIV-infected youth to adult care, which will guide in the development of an individualized plan for each youth. The plan should be introduced to the youth in early adolescence and modified as the youth approaches transition. Assessment of developmental milestones is important to define the readiness of the youth in assuming responsibility for his or her own care before initiating the transfer. Communication among all providers is essential and should include both personal contact and a written medical summary. Progress toward the transition should be tracked and, once completed, should be documented and assessed.

False negative DNA polymerase chain reaction in an infant with subtype C human immunodeficiency virus type 1 infection

Diagnosis of HIV infection in early infancy generally relies on detection of HIV proviral DNA by PCR. However, many of the HIV DNA PCR assays currently in use are either not optimized or have not been validated for diagnosis of infection with non-subtype B HIV. We report the case of an HIV-infected African American immigrant infant with subtype C HIV infection who tested negative repeatedly by HIV DNA PCR. Clinicians should be aware of this particular limitation of HIV DNA PCR assays, because it is likely that an increasing proportion of the HIV-infected infants seen in US centers will be infected with non-subtype B HIV.

Pharmacokinetics and pharmacodynamics of saquinavir in pediatric patients with human immunodeficiency virus infection

Our objective was to investigate the clinical pharmacologic characteristics of saquinavir given as a soft gelatin capsule, either alone or in combination with nelfinavir, to children and adolescents with human immunodeficiency virus infection.

Comprehensive pediatric human immunodeficiency virus care and treatment in Constanta, romania: Implementation of a program of Highly active antiretroviral therapy in a resource-poor setting

Background: Relatively few human immunodeficiency virus (HIV)-infected children worldwide have access to care and treatment. The Romanian-American Children’s Center, a collaborative project of a U.S. health care institution and the Romanian government, has established a comprehensive program of highly active antiretroviral therapy for children in Constanta, Romania. Objectives: To describe the design and outcomes of a program of pediatric HIV/acquired immunodeficiency syndrome (AIDS) care and treatment in a resource-poor setting. Setting: Outpatient center providing comprehensive primary and HIV/AIDS specialty care and treatment to all known HIV-infected children living in Constanta County, Romania. Outcomes: As of August 2003, a total of 452 children were receiving highly active antiretroviral therapy. Therapy has been well-tolerated, with ~90% of children continuing to receive treatment after a median duration of follow-up of 67 weeks. Normal weight and height growth velocities have been observed among treated children. Marked decreases have been observed in rates of hospitalization and mortality. The mean change in CD4+ lymphocyte count for 173 children who have both a baseline count and at least 1 follow-up count is +284 cells/μL (P < 0.0001). Conclusions: Highly active antiretroviral therapy can be administered safely and effectively to children in a resource-poor setting, with outcomes comparable with those observed in U.S. pediatric antiretroviral clinical trials.

Long-term Follow-up of 414 HIV-Infected Romanian Children and Adolescents Receiving Lopinavir/Ritonavir-Containing Highly Active Antiretroviral Therapy

BACKGROUND. There are no published reports of the long-term safety and effectiveness of highly active antiretroviral therapy for children and adolescents living in resource-limited settings or of large cohorts of HIV-infected children and adolescents treated long-term (>48 weeks) with lopinavir/ritonavir-containing highly active antiretroviral therapy. OBJECTIVES. The purpose of this work was to evaluate the long-term outcomes of treatment of HIV-infected children and adolescents with lopinavir/ritonavir-containing highly active antiretroviral therapy in a resource-limited setting. METHODS. We studied an inception cohort of 414 HIV-infected children receiving lopinavir/ritonavir-containing highly active antiretroviral therapy between November 2001 and August 2006 at the Romanian-American Childrens Center in Constanta, Romania. The center provides comprehensive primary and HIV specialty care and treatment to all known HIV-infected children and adolescents living in Constanta. We measured safety and effectiveness by the percentage of children remaining on treatment, rates of mortality, and changes in plasma HIV RNA concentrations and CD4+ lymphocyte counts. RESULTS. The study population consisted predominantly of antiretroviral drug–experienced older children and adolescents with advanced HIV disease. Treatment was well tolerated, with 337 children (81%) remaining on therapy after a median duration of >4 years. Thirty-seven deaths occurred; the death rate compared favorably to prospectively collected historical data. The most recent on-treatment plasma HIV RNA concentration was <400 copies per milliliter in 192 of 265 children tested. The mean baseline CD4+ lymphocyte count was 292 cells per microliter (n = 299); the mean change from baseline was +266 (n = 284), +317 (n = 260), +343 (n = 176), and +270 cells per microliter (n = 121) after 1, 2, 3, and 4 years of treatment, respectively. CONCLUSIONS. Highly active antiretroviral therapy can be administered safely and effectively to children and adolescents in resource-limited settings. Lopinavir/ritonavir-containing highly active antiretroviral therapy is a safe, effective, and durable treatment option for antiretroviral drug–experienced older children and adolescents with advanced HIV disease.

Infant Feeding and Transmission of Human Immunodeficiency Virus in the United States

Physicians caring for infants born to women infected with HIV are likely to be involved in providing guidance to HIV-infected mothers on appropriate infant feeding practices. It is critical that physicians are aware of the HIV transmission risk from human milk and the current recommendations for feeding HIV-exposed infants in the United States. Because the only intervention to completely prevent HIV transmission via human milk is not to breastfeed, in the United States, where clean water and affordable replacement feeding are available, the American Academy of Pediatrics recommends that HIV-infected mothers not breastfeed their infants, regardless of maternal viral load and antiretroviral therapy.

Ethics and the AIDS Pandemic in the Developing World

Traditional ethics provide insight, but often fall short of guiding the complex biomedical ethical concerns of research conducted in developing countries. The need to create research within a framework that is appropriate to the social, medical, and political context of developing countries is examined through the current AIDS pandemic in sub-Saharan Africa. A specific case study focuses on this issue.

Centralization of HIV services in HIV-positive African-American and Hispanic youth improves retention in care

Abstract African-American and Hispanic HIV-infected youth are a high risk group for not remaining in HIV care. We examined differences in retention in care among 174 HIV-infected African-American and Hispanic youth between 13 and 23 years old who presented for HIV primary care between 1 January 2002 and 31 August 2008. Patients were included in three service eras, based on when they entered the clinic: when no youth-specific services were available (the decentralized era), after formation of a youth clinic staffed by adolescent providers and a case-manager (the centralized era), and after educational activities and support groups were added and the social services staff were trained in the use of motivational interviewing (the centralized with supportive services era). Patient and attendance data for the 12-months following entry into care were captured. Retention in HIV care was examined using two different measures: adequate visit constancy (at least three quarters with at least one visit in each quarter) and having a gap in care (two consecutive medical visits ≥180 days apart). Adequate visit constancy improved by service era from 31% in the decentralized era to 57% in the centralized era and 65% in the centralized with supportive services era (p=0.01). The percent of patients with no gap in care remained stable at about 80% in the decentralized and centralized eras, but then increased to 96% in the centralized with supportive services era (p=0.04). Results suggest that centralizing youth-specific care and expanding youth services can improve retention in HIV care. These system changes should be considered when resources allow.

Associations of cytokines, sleep patterns, and neurocognitive function in youth with HIV infection

Youth infected with HIV at birth often have sleep disturbances, neurocognitive deficits, and abnormal psychosocial function which are associated with and possibly resulted from elevated blood cytokine levels that may lead to a decreased quality of life. To identify molecular pathways that might be associated with these disorders, we evaluated 38 HIV-infected and 35 uninfected subjects over 18-months for intracellular cytokine levels, sleep patterns and duration of sleep, and neurodevelopmental abilities. HIV infection was significantly associated with alterations of intracellular pro-inflammatory cytokines (TNF-α, IFN-γ, IL-12), sleep factors (total time asleep and daytime sleep patterns), and neurocognitive factors (parent and patient reported problems with socio-emotional, behavioral, and executive functions; working memory-mental fatigue; verbal memory; and sustained concentration and vigilance. By better defining the relationships between HIV infection, sleep disturbances, and poor psychosocial behavior and neurocognition, it may be possible to provide targeted pharmacologic and procedural interventions to improve these debilitating conditions.