BACKGROUND:This study measured serial plasma human immunodeficiency virus (HIV)-1-specific antibody (Ab) levels in children who initiated antiretroviral therapy (ART) prior to 2 years of age, and evaluated their relationship to peripheral blood HIV-1 RNA and DNA levels. METHODS:We studied 46 HIV-1-infected children, stratified by age at ART initiation (<3 mo, early therapy [ET]; >3 mo-2 years, late therapy [LT]) and by virologic response (R) or non-response (NR), before and up to 4 years following ART. We studied 20 HIV-1-uninfected children born to HIV-1-infected mothers (seroreverters [SR]) as controls. Plasma immunoglobulin G (IgG) Ab levels directed against HIV-1 envelope (gp160, gp41), gag (capsid, p24; matrix, p17), reverse transcriptase (p66/51), and integrase (p31) were serially measured using quantitative enzyme-linked immunosorbent assays. HIV-1 Ab rates of decline were estimated over the first 15 months of the study. RESULTS:The HIV-1 Ab rates of decline in the ET-R group were similar to those in the SR group for all Ab specificities, except for p17 (P = .01). Ab decline rates in the LT-R group and the NR group were significantly slower than in the SR group for all tested Ab specificities. After 1 year of age, Ab levels to p31 and p17 were significantly associated with HIV-1 RNA levels (P < .001); Ab levels to gp160 (P < .001) and gp41 (P < .001) were significantly associated with cell-associated HIV-1 DNA levels. CONCLUSIONS:Quantitative HIV-1-specific Ab levels may be useful for screening children on ART for viral suppression or for residual, cell-associated HIV-1 DNA levels. CLINICAL TRIALS REGISTRATION:NCT00000872.

Background: Women living with HIV (WLHIV) have increased risk of spontaneous preterm delivery (SPTD). We sought to identify plasma predictors of SPTD and their correlations with factors that increase the risk of SPTD, such as vitamin D deficiency and use of protease inhibitors. Design: Plasma was obtained from 103 WLHIV with SPTD (≤35 weeks gestation) and 205 controls with term deliveries (TDs; ≥37 weeds) matched to cases 2:1 by race and gestational age at blood draw. TNFα, IFNγ, IL6, IL8, IL1β, IL18, IL17, granulocyte colony stimulating factor (GCSF), MCP1, IP10, sIL2Rα, sCD14, vascular endothelial factor a, monocyte colony stimulation factor, GROα, MMP9, IL10, TGFβ, sCTLA4, and eicosanoids were compared between cases adjusting for known SPTD risk factors. Results: Participants had similar demographic characteristics, but cases had higher plasma HIV RNA, lower CD4 cells, and more advanced HIV disease compared with controls. High sIL2Rα was associated with increased risk of SPTD. High sCD14, GCSF, PGF2α, and 5-HEPE were marginally associated with increased risk of SPTD. Women who initiated protease inhibitors-containing antiretroviral treatment before or during the first trimester had higher levels of GCSF and 5-HEPE compared with women without such exposure before plasma collection. Vitamin D insufficiency was associated with higher inflammatory sCD14 and PGF2α, and lower anti-inflammatory 5-HEPE. Conclusions: The best plasma predictor of SPTD in WLHIV was sIL2Rα, a marker of T-cell activation. Markers of monocyte activation and eicosanoids were marginally increased in WLHIV and SPTD, suggesting that they may also play a role in the pathogenesis of this disorder.

In Nigeria, the incidence and prevalence of human immunodeficiency virus (HIV)-related neurocognitive impairment (NCI) are unknown and there currently exists little information related to the viral correlates rates of NCI. Therefore, studies were performed to examine the potential utility of applying an established neuropsychological (NP) screening battery and detailed NP testing to detect NCI and correlations with functional impairment and the presence of specific viral signatures among infected subjects. A total of 60 HIV-1 seropositive antiretroviral-naive individuals and 56 seronegative control subjects were administered the International HIV Dementia Scale (IHDS) and assessed for functional impairment using the Karnofsky performance status scale. Fifteen HIV-infected patients and 11 controls were also administered a detailed NP battery. Blood samples from eight infected subjects, three with evidence of NCI, were obtained for molecular analysis of HIV-1 strain. Unadjusted scores on the IHDS showed that, using a recommended total score cutoff of 10, 28.8 % of the HIV-1 seropositive and 16.0 % of seropositive individuals scored abnormally. Results from testing using the full NP battery showed that, overall, the HIV seropositive group performed worse than the seronegative group, with effect sizes spanning from small (0.25 on the trail making test A) to large (0.82 on action fluency), and an average effect size across the battery of 0.45, which approaches that which has been recorded in other international settings. Sequencing of partial pol amplicons from viral isolates revealed that two of three patients with NCI were infected with subtype G virus and 1 with the circulating recombinant form (CRF)02_AG; all four individuals without NCI were infected with CRF_02AG. These studies demonstrate the utility of the IHDS in identifying cognitive impairment among HIV infected individuals in Nigeria. Future studies aimed at examining the burden of NCI among the population of individuals with HIV-1 infection in Nigeria and which assess the virologic correlates will contribute to the evolving understanding of the pathogenetic factors that underlie this disorder.

Objective: Medication adherence is critical to the success of antiretroviral therapies for children and youth with perinatally acquired HIV. Factors that influence successful transition of medication responsibility from caregivers to youth are poorly understood. The purpose of this study was to evaluate the relationship of medication adherence with demographic, cognitive, academic, and behavioral characteristics. Methods: Randomly selected youth, N = 151, aged 8 to 18 years, completed cognitive and academic measures, and they and their caregivers completed questionnaires assessing behavior and emotional well-being. An announced pill count and questionnaires completed by youth and their caregivers were used to evaluate adherence. Results: Of 151 participants, 100 completed all adherence measures. Adherence rates varied by assessment method. Nonadherence (<90%) by pill count was associated with older child age, greater youth responsibility for medications, and other demographic and medication regimen variables. Verbal impairment predicted better self-reported adherence and reading problems predicted better self- and caregiver-reported adherence. Youth-reported locus of control was associated with pill count nonadherence, and poor relationships with parents were associated with youth-reported nonadherence. Conclusions: Consideration of youth cognitive or academic status may be helpful in evaluating medication adherence in patients with perinatally acquired HIV infection, particularly when using self- or caregiver reports to assess adherence. Vigilance for adherence problems is indicated when youth are older, responsible for medications, report poor caregiver relationships, and/or sense a lack of control over their lives.

Background: Hypercholesterolemia is common in perinatally HIV-infected (HIV+) children, but little is known about the clinical course and management in this population. Methods: We studied HIV+ children in a multisite prospective cohort study (Pediatric AIDS Clinical Trials Group 219C) and considered follow-up for 2 years after development of hypercholesterolemia. We estimated the time and factors associated with resolution of hypercholesterolemia and described changes in antiretroviral regimen and use of lipid-lowering medications. We defined incident hypercholesterolemia as entry total cholesterol (cholesterol) <220 mg/dL and 2 subsequent consecutive cholesterol ≥220 mg/dL and defined resolution of hypercholesterolemia as 2 consecutive cholesterol <200 mg/dL after incident hypercholesterolemia. Results: Among 240 incident hypercholesterolemia cases, 81 (34%) had resolution to normal cholesterol within 2 years of follow-up (median follow-up = 1.9 years). The median age of cases was 10.3 years with 54% non-Hispanic black and 53% male. Resolution to normal cholesterol was more likely in children who changed antiretroviral regimen (adjusted hazard ratio = 2.37, 95% confidence interval: 1.45 to 3.88) and who were 13 years and older (aHR = 2.39, 95% confidence interval: 1.33 to 4.27). Types of regimen changes varied greatly, and 15 children began statins. Conclusion: The majority of children who develop hypercholesterolemia maintain elevated levels over time, potentially placing them at risk for premature cardiovascular morbidity.

BACKGROUND:Highly active antiretroviral therapy (HAART) has improved human immunodeficiency virus (HIV)-associated morbidity and mortality. The bimodal mortality distribution in HIV-infected children makes it important to evaluate temporal effects of HAART among a birth cohort with long-term, prospective follow-up.METHODS:Perinatal AIDS Collaborative Transmission Study (PACTS)/PACTS-HIV Follow-up of Perinatally Exposed Children (HOPE) study was a Centers for Disease Control and Prevention-sponsored multicenter, prospective birth cohort study of HIV-exposed uninfected and infected infants from 1985 until 2004. Mortality was evaluated for the no/monotherapy, mono-/dual-therapy, and HAART eras, that is, 1 January 1986 through 31 December 1990, from 1 January 1991 through 31 December 1996, and 1 January 1997 through 31 December 2004.RESULTS:Among 364 HIV-infected children, 56% were female and 69% black non-Hispanic. Of 98 deaths, 79 (81%) and 61 (62%) occurred in children ≤3 and ≤2 years old, respectively. The median age at death increased significantly across the eras (P < .0001). The average annual mortality rates were 18 (95% confidence interval [CI], 11.6-26.8), 6.9 (95% CI, 5.4-8.8), and 0.8 (95% CI, 0.4-1.5) events per 100 person-years for the no/monotherapy, mono-/dual-therapy and HAART eras, respectively. The corresponding 6-year survival rates for children born in these eras were 57%, 76%, and 91%, respectively (P < .0001). Among children who received HAART in the first 6 months of age, the probability of 6-year survival was 94%. Ten-year survival rates for HAART and non-HAART recipients were 94% and 45% (P < .05). HAART-associated reductions in mortality remained significant after adjustment for confounders (hazard ratio, 0.3; 95% CI, .08-.76). Opportunistic infections (OIs) caused 31.8%, 16.9%, and 9.1% of deaths across the respective eras (P = .051).CONCLUSIONS:A significant decrease in annual mortality and a prolongation in survival were seen in this US perinatal cohort of HIV-infected children. Temporal decreases in OI-associated mortality resulted in relative proportional increases of non-OI-associated deaths.

The impact of behavioral functioning on medication adherence in children with perinatally acquired HIV infection is not well-explored, but has important implications for intervention. This report addresses the relationship between behavioral functioning and child self-report or caregiver report of medication adherence among children and adolescents enrolled in Pediatric AIDS Clinical Trials Group Protocol 219C (conducted 2000-2007). A total of 1134 participants, aged 3-17 years, received a behavioral evaluation and adherence assessment. Complete adherence was defined as taking 100% of prescribed antiretroviral medications during three days preceding the study visit. Multivariable logistic regression models were used to evaluate associations between adherence and behavioral functioning, adjusting for potential confounders, including demographic, psychosocial, and health factors. Children demonstrated higher than expected rates of behavioral impairment (≈7% expected with T > 65) in the areas of conduct problems (14%, z = 7.0, p < 0.001), learning problems (22%, z = 12.2, p < 0.001), somatic complaints (22%, z = 12.6, p < 0.001), impulsivity-hyperactivity (20%, z = 11.1, p < 0.001), and hyperactivity (19%, z = 10.6, p < 0.001). Children with behavioral impairment in one or more areas had significantly increased odds of nonadherence [adjusted odds ratio (aOR) = 1.49, p = 0.04]. The odds of nonadherence were significantly higher for those with conduct problems and general hyperactivity (aOR = 2.03, p = 0.005 and aOR = 1.68, p = 0.02, respectively). Psychosocial and health factors, such as recent stressful life events and higher HIV RNA levels, were also associated with nonadherence. Knowledge of behavioral, health, and social influences affecting the child and family should guide the development of appropriate, evidence-based interventions for medication adherence.

Medication adherence is critical for children's HIV treatment success, but obtaining accurate assessments is challenging when complex measurement technologies are not feasible. Our goal was to evaluate a multidimensional adherence interview designed to improve on existing adherence measures. Data from caregivers (N = 126) of perinatally infected children were analyzed to determine the ability of the revised interview guide to detect potential treatment nonadherence. Questions related to viral load (VL) on a bivariate level included proportion of doses taken in the previous 3 days and 6 months, caregivers' knowledge of prescribed dosing frequencies, and caregivers' reports of problems associated with medication administration. VL was not associated with 3-day recall of missed doses. In multivariate analyses, only caregiver knowledge of prescribed dosing frequencies was uniquely associated with VL. Our modified interview appears to successfully identify family struggles with adherence and to have the capacity to help clinicians address medication adherence challenges.

Substantial resources and patient commitment are required to successfully scale-up antiretroviral therapy (ART) and provide appropriate HIV management in resource-limited settings. We used pharmacy refill records to evaluate risk factors for loss to follow-up (LTFU) and non-adherence to ART in a large treatment cohort in Nigeria.We reviewed clinic records of adult patients initiating ART between March 2005 and July 2006 at five health facilities. Patients were classified as LTFU if they did not return >60 days from their expected visit. Pharmacy refill rates were calculated and used to assess non-adherence. We identified risk factors associated with LTFU and non-adherence using Cox and Generalized Estimating Equation (GEE) regressions, respectively. Of 5,760 patients initiating ART, 26% were LTFU. Female gender (p < 0.001), post-secondary education (p = 0.03), and initiating treatment with zidovudine-containing (p = 0.004) or tenofovir-containing (p = 0.05) regimens were associated with decreased risk of LTFU, while patients with only primary education (p = 0.02) and those with baseline CD4 counts (cell/ml(3)) >350 and <100 were at a higher risk of LTFU compared to patients with baseline CD4 counts of 100-200. The adjusted GEE analysis showed that patients aged <35 years (p = 0.005), who traveled for >2 hours to the clinic (p = 0.03), had total ART duration of >6 months (p<0.001), and CD4 counts >200 at ART initiation were at a higher risk of non-adherence. Patients who disclosed their HIV status to spouse/family (p = 0.01) and were treated with tenofovir-containing regimens (p < or = 0.001) were more likely to be adherent.These findings formed the basis for implementing multiple pre-treatment visit preparation that promote disclosure and active community outreaching to support retention and adherence. Expansion of treatment access points of care to communities to diminish travel time may have a positive impact on adherence.

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.

Scores from the Alcohol Use Disorders Identification Test (AUDIT) and the Center for Epidemiological Studies Depression Scale (CES-D) administered to both antiretroviral therapy (ART)-experienced and -naive adults in HIV care in Nigeria were evaluated for association with participant characteristics and ART adherence measured by pharmacy records. Participants included 222 ART-experienced and 177 ART-naive adults, of whom 47 (12%) had AUDIT ≥8, 29 (7%) an AUDIT ≥10, 52 (13%) a CES-D ≥16, and 25 (6%) a CES-D ≥21. An elevated AUDIT score was more frequent among ART-naive and men, while disclosure of HIV status to others was associated with lower scores. An elevated CES-D score was more frequent among ART-naive and those with lower educational level, while disclosure of HIV status and choosing to be interviewed in English rather than Hausa was associated with lower scores. An elevated CES-D score was associated with poor adherence.

ObjectiveTo evaluate the relationship between cognitive functioning and medication adherence in children and adolescents with perinatally acquired HIV infection.MethodsChildren and adolescents, ages 318 (N 1,429), received a cognitive evaluation and adherence assessment. Multiple logistic regression models were used to identify associations between adherence and cognitive status, adjusting for potential confounding factors.ResultsChildrens average cognitive performance was within the low-average range; 16 of children were cognitively impaired (MDI/FSIQ 70). Cognitive status was not associated with adherence to full medication regimens; however, children with borderline/low average cognitive functioning (IQ 7084) had increased odds of nonadherence to the protease inhibitor class of antiretroviral therapy. Recent stressful life events and child health characteristics, such as HIV RNA detectability, were significantly associated with nonadherence.ConclusionCognitive status plays a limited role in medication adherence. Child and caregiver psychosocial and health characteristics should inform interventions to support adherence.

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.

Background: Parent/caregiver or child/youth self-report and pill counts are commonly used methods for assessing adherence to antiretroviral therapy among children and youth with HIV. The purpose of this study was to compare these different methods with one another and with viral load. Methods: Randomly selected parent/caregiver and child/youth dyads were interviewed using several adherence self-report measures and an announced pill count was performed. Adherence assessment methods were compared with one another and their relative validity was assessed by comparison with the child’s viral load close to the time of the interview or pill count, adjusting for primary caregiver, child age, and child disclosure of the diagnosis. Results: There were 151 evaluable participants. Adherence rate by pill count was ≥90% in 52% of participants, was significantly associated with log(RNA) viral load (p = .032), and had significant agreement with viral load <400 copies/mL. However, pill count data were incomplete for 26% of participants. With similar proportions considered adherent, a variety of self-report adherence assessment methods also were associated with log(RNA) viral load including: “no dose missed within the past 1 month” (p = .054 child/youth interview, p = .004 parent/caregiver interview), and no barrier to adherence identified (p = .085 child/youth interview, p = .015 parent/caregiver interview). Within-rater and inter-rater agreement was high among self-report methods. Three day recall of missed doses was not associated with viral load. Conclusion: Findings demonstrate the validity of adherence assessment strategies that allow the parent/caregiver or child/youth to report on adherence over a longer period of time and to identify adherence barriers. Adherence assessed by announced pill count was robustly associated with viral load, but there was incomplete data for many participants.

ObjectiveThe purpose of the study is to describe allocation of responsibility for illness management in families of children and adolescents perinatally infected with HIV.MethodsA total of 123 youth (ages 818) and caregivers completed family responsibility and medication adherence questionnaires as part of a substudy of Pediatric AIDS Clinical Trials Group protocol 219c.ResultsApproximately one-fourth of the youth reported being fully responsible for taking medications. A smaller percentage of caregivers reported full youth responsibility. Older youth and caregivers of older youth reported higher degree of youth responsibility for medication-related tasks, though age was unrelated to adherence. Caregiver report of greater responsibility for medications was associated with better adherence.ConclusionsCaregivers are likely to transition responsibility for HIV care to older youth but this transition was not always successful as evidenced by poor medication adherence. Interventions supporting successful transition may improve adherence and subsequently health outcomes in pediatric HIV.

Context: Antiretroviral therapy has been associated with hypercholesterolemia in HIV-infected children. Few longitudinal studies have been conducted to examine this association, however. Objective: To evaluate the incidence of and risk factors for development of hypercholesterolemia in a large pediatric study. Design: Prospective cohort study (Pediatric AIDS Clinical Trials Group 219C). Participants: A total of 2122 perinatally HIV-infected children free of hypercholesterolemia at entry. Outcome: Development of hypercholesterolemia (total cholesterol ≥220 mg/dL at 2 consecutive visits). Cox proportional hazards models were used to evaluate risk factors. Results: Thirteen percent of children had hypercholesterolemia at entry, and an additional 13% developed hypercholesterolemia during follow-up for an incidence rate of 3.4 cases per 100 person-years (95% confidence interval [CI]: 3.0 to 3.9). After adjustment for age, boosted protease inhibitor (PI) use (hazard ratio [HR] = 13.9, 95% CI: 6.73 to 28.6), nonboosted PI use (HR = 8.65, 95% CI: 4.19 to 17.9), and nonnucleoside reverse transcriptase inhibitor use (HR = 1.33, 95% CI: 1.04 to 1.71) were associated with increased risk of hypercholesterolemia, and higher viral load was protective (>50,000 vs. ≤400 copies/mL; HR = 0.59, 95% CI: 0.39 to 0.90). Self-reported adherent subjects had higher risk. Conclusions: PIs were significant risk factors for hypercholesterolemia. Higher viral load was protective and may reflect nonadherence. Further follow-up is critical to evaluate long-term consequences of chronic PI exposure and hypercholesterolemia.

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.

Although parents and caregivers may have primary responsibility for their children's medication- taking, surprisingly few studies have examined caregiver psychosocial correlates of children's adherence to antiretroviral therapy (ART). This cross-sectional, descriptive study examined the relationship between caregiver psychosocial characteristics and medication adherence among children with HIV. Fifty-four caregivers of children with HIV completed a demographic questionnaire, the Parenting Stress Index, the Brief Symptom Inventory, the Family Support Scale, and the Support Functions Scale. Adherence to ART was measured with children's 6-month pharmacy refill histories. Children and caregivers were primarily African American, urban, and poor (63% reported <$15,000 annual household income). Univariate analyses showed that an adherent classification (>/= 80% refill rate) was associated with shorter duration of highly active antiretroviral therapy (HAART) treatment, nondisclosure of the HIV diagnosis to the child, lower caregiver income level, having a nonbiologically related caregiver, and less caregiver psychiatric distress. In a multivariate logistic regression, duration of child's HAART treatment, child HIV disclosure status, caregiver income, and caregiver psychiatric distress accounted for 63% of the variance in adherence. Findings highlight the complexity of children's adherence to ART and the need for multicenter studies with greater sample sizes to explore in more detail the effects of caregiver psychological distress and child HIV disclosure status on adherence as well as the ways in which regimen fatigue and adherence fluctuate over time.