Tremendous success in the prevention and treatment of pediatric HIV in high-resource countries has changed the face of the epidemic. A perinatally HIV-infected child now faces a chronic disease rather than a progressive, fatal one. However, these successes pose new challenges as perinatally HIV-infected youth survive into adulthood. These include maintaining adherence to long-term, likely life-long therapy; selecting successive antiretroviral drug regimens, given the limited availability of pediatric formulations and the lack of pharmacokinetic and safety data in children; and overcoming extensive drug resistance in multi-drug-experienced children. Pediatric HIV care now focuses on morbidity related to long-term HIV infection and its treatment. Survival into adulthood of perinatally HIV-infected youth in high-resource countries encourages expansion of pediatric treatment programs in low-resource countries, where most HIV-infected children live, and provides important lessons about how the epidemic changes with increasing access to antiretroviral therapy for children.

Growing Up with HIV: Children, Adolescents, and Young Adults with Perinatally Acquired HIV Infection*

BACKGROUND. Little is known concerning the impact of HIV status disclosure on quality of life, leaving clinicians and families to rely on research of children with other terminal illnesses. OBJECTIVES. The purpose of this work was to examine the impact of HIV disclosure on pediatric quality of life and to describe the distribution of age at disclosure in a perinatally infected pediatric population. METHODS. A longitudinal analysis was conducted of perinatally HIV-infected youth ≥5 years of age enrolled in a prospective cohort study, Pediatric AIDS Clinical Trials Group 219C, with ≥1 study visit before and after HIV disclosure. Age-specific quality-of-life instruments were completed by primary caregivers at routine study visits. The distribution of age at disclosure was summarized. Six quality-of-life domains were assessed, including general health perception, symptom distress, psychological status, health care utilization, physical functioning, and social/role functioning. For each domain, mixed-effects models were fit to estimate the effect of disclosure on quality of life. RESULTS. A total of 395 children with 2423 study visits were analyzed (1317 predisclosure visits and 1106 postdisclosure visits). The median age at disclosure was estimated to be 11 years. Older age at disclosure was associated with earlier year of birth. Mean domain scores were not significantly different at the last undisclosed visit compared with the first disclosed visit, with the exception of general health perception. When all of the visits were considered, 5 of 6 mean domain scores were lower after disclosure, although the differences were not significant. In mixed-effects models, disclosure did not significantly impact quality of life for any domain. CONCLUSIONS. Age at disclosure decreased significantly over time. There were no statistically significant differences between predisclosure and postdisclosure quality of life; therefore, disclosure should be encouraged at an appropriate time.

Impact of disclosure of HIV infection on health-related quality of life among children and adolescents with HIV infection.

Health-related quality of life in children and adolescents with sickle cell disease.

Highly active antiretroviral therapy (HAART) results in marked survival benefits for HIV-infected people.1,2 In contrast to adults, who may defer HAART for several years, nearly half of HIV-1 infected children in Africa will die by the age of 2 if they are not treated.3,4 By 2005 in Africa, where ∼90% of the world's HIV-infected children reside, children represented 13% of the population in need of antiretroviral treatment (ART) and only ∼5% of the population receiving ART.5,6 The number of children receiving ART has since increased; however, children are still less likely than adults to receive therapy.5

Many factors impede the use of HAART in resource-limited settings, particularly in pediatric populations. Lack of infrastructure, health care professionals, and technology to diagnose HIV-1 and monitor treatment have initially delayed treatment of both adults and children.7 The threat of poor adherence and viral resistance continues to be a concern in resource-limited settings.8,9 Children face additional barriers to treatment including dosing, formulations, higher costs for pediatric antiretroviral drugs, and high infant mortality rates.3,10–13

Beginning in 2004, African countries began expanding access to antiretroviral medications as funding became available.14,15 Better descriptions of clinical diagnosis, staging, and management of HIV-infected children facilitated scale-up of treatment.16 A number of publications in which treatment outcomes for pediatric populations in resource-limited settings were described have recently emerged. These studies, including 2 recent reviews by Sutcliffe et al14 and Ciaranello et al,17 reference outcomes from developed-countries (DCs) publications for informal comparison; however, no study has systematically compared outcomes and characteristics of pediatric ART between resource-limited countries (RLCs) and DCs.

The purpose of this study was to review the literature to quantify and compare major clinical end points and baseline characteristics for children receiving HAART in DCs versus RLCs.

Post-HAART outcomes in pediatric populations: comparison of resource-limited and developed countries.

Treatment of HIV-infected children with highly active antiretroviral therapy (HAART) has led to vastly improved outcomes, including reduced mortality,1 decreased incidence of opportunistic infections,2 and improved quality of life.3,4 Despite these advances, metabolic complications related to antiretroviral treatment (ART) have been noted, including delayed puberty, fat redistribution, insulin resistance. and dyslipidemia.5–8

Several cross-sectional studies have found the use of protease inhibitors (PIs) to be associated with elevated cholesterol in children.9–12 Other studies that examined the incidence of hypercholesterolemia among children on PI therapy observed an increase in cholesterol levels over time.13–15

A few longitudinal studies have also been conducted to examine the association between antiretroviral therapy and incidence of high cholesterol and other metabolic disturbances in HIV-infected children. Beregszaszi et al16 identified PI use as an independent predictor of metabolic disturbance (defined as abnormally high levels of insulin, cholesterol, or triglycerides). Rhoads et al17 compared nonfasting lipid levels in children on HAART with PI, HAART without PI, or no HAART. Both types of HAART regimens were associated with an increase in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). PI use was independently associated with incidence of high total cholesterol among children participating in the Perinatal AIDS Collaborative Transmission Study–HIV Follow-up After Perinatal Exposure (PACTS-HOPE) study.18 All these studies were relatively small, however, with fewer than 200 subjects.

For this analysis, we examined the incidence of hypercholesterolemia in a large prospectively followed cohort of perinatally HIV-infected children, while adjusting for potentially confounding factors. In addition, we evaluated whether ART, particularly PIs, was associated with increased incidence. This study adds to the earlier cross-sectional evaluation of hypercholesterolemia in this cohort,11 because the ART exposure in our study preceded the development of hypercholesterolemia.

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Association of hypercholesterolemia incidence with antiretroviral treatment, including protease inhibitors, among perinatally HIV-infected children.

BACKGROUND. HIV/AIDS mortality rates in the United States are declining; pediatric HIV has become a chronic disease, with quality of life (QoL) outcomes assuming greater importance. OBJECTIVES. To compare QoL among HIV-infected and uninfected children and to assess the impact of different antiretroviral regimens on QoL among HIV-infected children. METHODS. Perinatally exposed, HIV-infected (N = 1847) and uninfected (N = 712) children and adolescents were studied. Among infected children, 1283 were available for the antiretroviral regimen analysis. QoL domain scores were assessed for subjects 6 months to 4 years, 5 to 11 years, and 12 to 21 years of age, and the impact of infection status and alternative treatment regimens on QoL domains was evaluated. RESULTS. HIV infection was associated with significantly worse mean adjusted scores for functional status among children 6 months to 4 years of age and health perceptions, physical resilience, physical functioning, and social/role functioning among those 5 to 11 years of age. However, uninfected children 5 to 11 years of age reported significantly worse psychological functioning. HIV-infected children (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. CONCLUSIONS. Generally parents of HIV-infected children 6 months to 4 years and 5 to 11 years of age generally reported lower mean QoL scores than did parents of uninfected children, although worse psychological functioning was reported for uninfected children. HIV-infected adolescents not receiving antiretroviral treatment had worse health perceptions and symptoms. We found no consistent QoL differences among children receiving different antiretroviral regimens.

B. Dashefsky

Papers

Quality of Life for Children and Adolescents: Impact of HIV Infection and Antiretroviral Treatment