A cluster randomised controlled trial of an early childhood parenting programme delivered through early childhood education centres in rural Zimbabwe.

BACKGROUND: Early childhood is a critical period for child development. Effective approaches to support families in low-resource settings in the use of responsive and stimulating parenting are needed. AIM: The aim of this study was to examine the effects of the Reach Up early childhood parenting programme on children's development, parenting attitudes and practices, when delivered through early childhood development (ECD) centres in Zimbabwe. METHODS: A cluster randomised controlled trial was conducted in Sanyati, a rural district in Zimbabwe. Twenty-four of 51 available centres were randomised to intervention (n = 12) or control (n = 12) groups. Sixteen mothers with a child aged 12-30 months were recruited from each centre's catchment area (n = 189 intervention; n = 193 control). The intervention comprised two home visits per month delivered by centre teaching assistants over a period of 27 months. Primary outcomes were child Developmental Quotient (DQ), Language, Eye and Hand coordination, Performance and Practical Reasoning subscale scores assessed at follow-up. Secondary outcomes were mothers' attitudes about child development, parenting practices and maternal depressive symptoms all measured at baseline and follow-up. Intention to treat analyses was conducted using mixed-effects regression models with the standard error adjusted for cluster and inverse proportionality weights to adjust for attrition. Significance was set at P < 0.05. RESULTS: A total of 285 (74.6%) of 382 children enrolled were tested, with 97 children lost to follow-up. The intervention improved the children's DQ by 3.55 points (95% CI 0.82 to 6.28), Eye and Hand by 3.58 (95% CI 0.59 to 6.56) and Practical Reasoning by 4.19 (95% CI 0.96 to 7.42). No significant improvements to Performance or Language scores, parenting attitudes, parenting practices and depressive symptoms were identified. CONCLUSIONS: A home visiting intervention delivered by ECD teaching assistants promoted children's development. This suggests that outreach from preschools may be an effective platform for delivery of parenting interventions.

Integrating a Parenting Intervention With Routine Primary Health Care: A Cluster Randomized Trial.

OBJECTIVE: More than 200 million children globally do not attain their developmental potential. We hypothesized that a parent training program could be integrated into primary health center visits and benefit child development. METHODS: We conducted a cluster randomized trial in the Caribbean (Jamaica, Antigua, and St Lucia). Fifteen centers were randomly assigned to the control (n = 250 mother-child pairs) and 14 to the intervention (n = 251 mother-child pairs) groups. Participants were recruited at the 6- to 8-week child health visit. The intervention used group delivery at 5 routine visits from age 3 to 18 months and comprised short films of child development messages, which were shown in the waiting area; discussion and demonstration led by community health workers; and mothers' practice of activities. Nurses distributed message cards and a few play materials. Primary outcomes were child cognition, language, and hand-eye coordination and secondary outcomes were caregiver knowledge, practices, maternal depression, and child growth, measured after the 18-month visit. RESULTS: Eight-five percent of enrolled children were tested (control = 210, intervention = 216). Loss did not differ by group. Multilevel analyses showed significant benefits for cognitive development (3.09 points; 95% confidence interval: 1.31 to 4.87 points; effect size: 0.3 SDs). There were no other child benefits. There was a significant benefit to parenting knowledge (treatment effect: 1.59; 95% confidence interval: 1.01 to 2.17; effect size: 0.4). CONCLUSIONS: An innovative parenting intervention, requiring no additional clinic staff or mothers' time, was integrated into health services, with benefits to child cognitive development and parent knowledge. This is a promising strategy that merits further evaluation at scale.

Comparison of plasmapheresis and intravenous immunoglobulin as maintenance therapies for juvenile myasthenia gravis.

IMPORTANCE: Juvenile myasthenia gravis (MG) is a relatively rare autoimmune disorder. The comparative efficacy of plasmapheresis (PLEX) vs immunoglobulin as maintenance therapy is unclear for this childhood disease. OBJECTIVE: To determine whether PLEX or intravenous immunoglobulin (IVIG) therapy is more effective as maintenance therapy in this disease. DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis over a 33-year period involved 54 children and adolescents with juvenile MG at a specialized neuromuscular clinic and electromyography laboratory at a tertiary care academic pediatric hospital. INTERVENTIONS: Plasmapheresis and IVIG. MAIN OUTCOMES AND MEASURES: Response to treatment was measured by both improvement in objective physical examination findings and the patients' reported improvement in symptoms and functional abilities. RESULTS: Subjective and objective outcomes correlated well. Both PLEX and IVIG had high response rates. Of the 27 patients with generalized juvenile MG receiving PLEX, IVIG, or both treatments, 7 of 7 patients treated with PLEX alone responded, 5 of 10 patients treated with IVIG alone responded, and 9 of 10 patients who received both responded. There was a significant difference in response rates between patients who received PLEX vs IVIG (P = .04). The youngest age at which PLEX was initiated via peripheral venous access was 9 years, while the youngest child who received IVIG was 9 months old. Thymectomy was performed in 17 children, of whom 11 experienced significant postoperative improvement. CONCLUSIONS AND RELEVANCE: This study provides class III evidence that PLEX and IVIG both have high response rates as maintenance therapies and are reasonable therapeutic options for juvenile MG. Plasmapheresis may have a more consistent response rate than IVIG in this setting. These findings will provide some guidance regarding the approach to therapy for juvenile MG, especially as the results differ somewhat from those of studies focusing on adult MG.

Inequality in early childhood: risk and protective factors for early child development.

Inequality between and within populations has origins in adverse early experiences. Developmental neuroscience shows how early biological and psychosocial experiences affect brain development. We previously identified inadequate cognitive stimulation, stunting, iodine deficiency, and iron-deficiency anaemia as key risks that prevent millions of young children from attaining their developmental potential. Recent research emphasises the importance of these risks, strengthens the evidence for other risk factors including intrauterine growth restriction, malaria, lead exposure, HIV infection, maternal depression, institutionalisation, and exposure to societal violence, and identifies protective factors such as breastfeeding and maternal education. Evidence on risks resulting from prenatal maternal nutrition, maternal stress, and families affected with HIV is emerging. Interventions are urgently needed to reduce children's risk exposure and to promote development in affected children. Our goal is to provide information to help the setting of priorities for early child development programmes and policies to benefit the world's poorest children and reduce persistent inequalities.

Early childhood stunting and later fine motor abilities.

AIM: The aim of this study was to determine the effects of early childhood stunting (height for age 2SD or more below reference values) and interventions on fine motor abilities at 11 to 12 years, and the relationship between fine motor abilities and school achievement and intelligence. METHOD: A cohort of stunted children who had participated in a randomized trial of psychosocial stimulation and/or nutritional supplementation in early childhood was compared with a group of non-stunted children. Fine motor abilities were assessed in 116 stunted (67 males, 49 females) and 80 non-stunted children (43 males, 37 females) at a mean age of 11 years 8 months (SD 4.3 mo) and 11 years 9 months (SD 3.8 mo) respectively. Testers were blind to the children's group assignment. RESULTS: Two fine motor factors were derived: rapid sequential continuous movements (RSCM) and dexterity. No effect of the early intervention was found. RSCM scores were lower in the stunted group than in the non-stunted group (p=0.01), but differences in dexterity were not significant (p=0.18) after adjusting for social background. Among stunted children, the RSCM score was significantly associated with IQ (p=0.04) and school achievement (all p<0.05). INTERPRETATION: Stunting in early childhood is associated with poor scores on tests of rapid sequential continuous hand movements in later childhood. Children with poorer scores are at greater risk for low IQs and low levels of school achievement.

Early childhood stunting is associated with poor psychological functioning in late adolescence and effects are reduced by psychosocial stimulation.

Stunting is associated with deficits in cognition and school achievement from early childhood to late adolescence; however, there has been little investigation of emotional and behavioral outcomes. The objective of this study was to determine whether linear growth retardation (stunting) in early childhood is associated with poorer psychological functioning in late adolescence. The study was a prospective cohort study of stunted and nonstunted children. Participants were identified at age 9-24 mo by a survey of poor neighborhoods in Kingston, Jamaica, and a 2-y intervention trial of supplementation and stimulation was conducted in the stunted children. Psychological functioning was assessed at age 17 y in 103 of 129 stunted children enrolled and 64 of 84 nonstunted participants. Anxiety, depressive symptoms, self-esteem, and antisocial behavior were reported by participants using interviewer-administered questionnaires and attention deficit, hyperactivity, and oppositional behavior were reported by parent interviews. The stunted participants reported significantly more anxiety (regression coefficient = 3.03; 95% CI = 0.99, 5.08) and depressive symptoms (0.37; 95% CI = 0.01, 0.72) and lower self-esteem (-1.67; 95% CI = -0.38, -2.97) than nonstunted participants and were reported by their parents to be more hyperactive (1.29; 95% CI = 0.12, 2.46). Effect sizes were 0.4-0.5 SD. Participants who received stimulation in early childhood differed from the nonstunted group in hyperactivity only. Children stunted before age 2 y thus have poorer emotional and behavioral outcomes in late adolescence. The findings expand the range of disadvantages associated with early stunting, which affects 151 million children <5 y old in developing countries.

Effects of psychosocial stimulation and dietary supplementation in early childhood on psychosocial functioning in late adolescence: follow-up of randomised controlled trial.

OBJECTIVE: To determine whether dietary supplementation or psychosocial stimulation given to growth retarded (stunted) children age 9-24 months has long term benefits for their psychosocial functioning in late adolescence. DESIGN: Sixteen year follow-up study of a randomised controlled trial. SETTING: Poor neighbourhoods in Kingston, Jamaica. PARTICIPANTS: Of 129 stunted children identified at age 9-24 months, 103 adolescents aged 17-18 were followed up. INTERVENTION: Supplementation with 1 kg milk based formula each week or psychosocial stimulation (weekly play sessions with mother and child), or both, for two years. MAIN OUTCOME MEASURES: Anxiety, depression, self esteem, and antisocial behaviour assessed by questionnaires administered by interviewers; attention deficit, hyperactivity, and oppositional behaviour assessed by interviews with parents. RESULTS: Primary analysis indicated that participants who received stimulation had significantly different overall scores from those who did not (F = 2.047, P = 0.049). Supplementation had no significant effect (F = 1.505, P = 0.17). Participants who received stimulation reported less anxiety (mean difference - 2.81, 95% confidence interval - 5.02 to - 0.61), less depression (- 0.43, - 0.78 to - 0.07), and higher self esteem (1.55, 0.08 to 3.02) and parents reported fewer attention problems (- 3.34, - 6.48 to - 0.19). These differences are equivalent to effect sizes of 0.40-0.49 standard deviations. CONCLUSIONS: Stimulation in early childhood has sustained benefits to stunted children's emotional outcomes and attention.

Association of CD4+ T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy.

BACKGROUND: In a cohort of children receiving highly active antiretroviral therapy (HAART) with sustained plasma HIV-1 RNA < 50 copies/mL, children who reached undetectable RNA after week 8 (slow responders, median: week 20) had higher HIV-1 intracellular DNA (HIV-1 DNA) and equal or greater CD4+ T-lymphocyte counts compared with children who reached undetectable plasma HIV-1 RNA by week 8 (rapid responders) throughout HAART. OBJECTIVE: To determine whether levels of T-cell receptor excision circles (TRECs) could explain the apparent inconsistency between the quantity of HIV-1 DNA and CD4+ T-lymphocyte counts in HIV-1-infected children receiving HAART with sustained virologic suppression. METHODS: T-cell receptor excision circles and HIV-1 DNA and plasma HIV-1 RNA were quantified longitudinally by PCR in 31 children (median age, 5.6 years) with sustained undetectable plasma HIV-1 RNA for >104 weeks of HAART. RESULTS: There was a positive correlation between TREC and HIV-1 DNA during HAART, notably at weeks 48 and 80 (P < .004). During the early stage of HAART, TREC levels positively correlated with CD4+ T-lymphocyte percentages (P < .02) and naive CD4+ T-lymphocyte counts (P < .001) and percentages (P = .05). Median TREC levels were consistently equal or higher in slow responders compared with rapid responders (P < .001) despite slow responders having consistently greater quantities of HIV-1 DNA. CONCLUSION: To maintain adequate levels of CD4+ T-lymphocytes, children with high HIV-1 DNA maintain high levels of TREC while receiving HAART. Thus, a thymic control mechanism is required to maintain new CD4+ T lymphocytes in the presence of persistent virus. CLINICAL IMPLICATIONS: The TREC level is a useful marker of thymic function in HIV-infected children.

Effects of early childhood psychosocial stimulation and nutritional supplementation on cognition and education in growth-stunted Jamaican children: prospective cohort study.

Growth retardation affects about a third of children younger than age 5 years in developing countries and is associated with poor development. Previously, we did a trial of nutritional supplementation and psychosocial stimulation in stunted children aged 9-24 months. Non-stunted children were also assessed. Both types of intervention improved development. We now present the effects of early interventions on cognition and education in 103 of the 129 stunted children and compare them with 64 of the 84 non-stunted children now aged 17-18 years. We recorded no significant effects of nutritional supplementation. Compared with no intervention, stimulation resulted in higher full scale IQ scores (coefficient 0.38, 95% CI 0.06-0.71, p=0.02) and higher scores on the verbal subscale (0.37, 0.07-0.68, p=0.02), Peabody picture vocabulary test (7.84, 0.73-14.95, p=0.03), verbal analogies (0.26, 0.03-0.49, p=0.03), and reading tests (4.73, 1.31-8.14, p=0.007, and 2.7, 1.12-4.37, p=0.001). Overall, stunted non-stimulated participants had significantly poorer scores than the non-stunted group on 11 of 12 cognitive and educational tests. Stunting in early childhood is associated with cognitive and educational deficits in late adolescence, which are reduced by stimulation at a young age.

Zinc supplementation and psychosocial stimulation: effects on the development of undernourished Jamaican children.

BACKGROUND: Undernourished children have poor levels of development that benefit from stimulation. Zinc deficiency is prevalent in undernourished children and may contribute to their poor development. OBJECTIVE: We assessed the effects of zinc supplementation and psychosocial stimulation given together or separately on the psychomotor development of undernourished children. DESIGN: This was a randomized controlled trial with 4 groups: stimulation alone, zinc supplementation alone, both interventions, and control (routine care only). Subjects were 114 children aged 9-30 mo and below -1.5 z scores of the National Center for Health Statistics weight-for-age references who were recruited from 18 health clinics. Clinics were randomly assigned to receive stimulation or not; individual children were randomly assigned to receive zinc or placebo. The stimulation program comprised weekly home visits during which play was demonstrated and maternal-child interactions were encouraged. The supplementation was 10 mg Zn as sulfate daily or placebo. Development (assessed by use of the Griffiths Mental Development Scales), length, and weight were measured at baseline and 6 mo later. Weekly morbidity histories were taken. RESULTS: Significant interactions were found between zinc supplementation and stimulation. Zinc benefited the developmental quotient only in children who received stimulation, and benefits from zinc to hand and eye coordination were greater in stimulated children. Zinc supplementation alone improved hand and eye coordination, and stimulation alone benefited the developmental quotient, hearing and speech, and performance. Zinc supplementation also reduced diarrheal morbidity but did not significantly improve growth. CONCLUSION: Zinc supplementation benefits development in undernourished children, and the benefits are enhanced if stimulation is also provided.

An MDR1-3435 variant is associated with higher plasma nelfinavir levels and more rapid virologic response in HIV-1 infected children.

OBJECTIVE: The multidrug-resistance transporter gene (MDR1) encoding for P-glycoprotein (P-gp) and genes encoding for isoenzymes of cytochrome P450 (CYP) have an important role in transport and metabolism of antiretroviral agents. This research examined the impact of single nucleotide polymorphisms (SNP) of MDR1 and CYP genes on nelfinavir and efavirenz pharmacokinetics and the response to highly active antiretroviral therapy (HAART) in HIV-1 infected children. METHODS: Seventy-one HIV-1-infected children from PACTG 382 receiving nelfinavir, efavirenz and one or two nucleoside reverse transcriptase inhibitors had genomic DNA from PBMC evaluated for MDR1 and CYP SNP by real-time PCR. Plasma drug concentrations, CD4 lymphocyte counts and HIV-1 RNA were measured during HAART. RESULTS: The frequencies of C/C, C/T and T/T genotypes in the MDR1-3435-C-->T polymorphisms were 44% (n = 31), 46% (n = 33) and 10% (n = 7), respectively. Ninety-one percent of children with the C/T genotype reached plasma HIV-1 RNA < 400 copies/ml by week 8 compared to 59% of children with the C/C genotype (P = 0.01). Children with the C/T genotypes had higher 8 h postdose concentration (P = 0.02) and lower clearance rate (P = 0.04) for nelfinavir compared to those with the C/C genotype. The seven children with the T/T genotype had nelfinavir pharmacokinetics and virologic response similar to those with the C/C genotype. No compensatory polymorphisms were observed between MDR1 and CYP genotypes. CONCLUSIONS: HIV-1 infected children with the MDR1-3435-C/T genotype had more rapid virologic responses to HAART at week 8 with higher plasma nelfinavir concentrations compared to those with the C/C genotype. These findings suggest that P-gp may play an important role in the pharmacokinetics and virologic response to HAART containing nelfinavir.

Psychosocial intervention improves the development of term low-birth-weight infants.

It is estimated that 11% of births in developing counties are term low-birth-weight (LBW); however, there is limited information on the development of these infants. Our objectives were to determine the effect of psychosocial intervention on the development of LBW infants and to compare term LBW and normal-birth-weight (NBW) infants. Term LBW (n = 140) and NBW infants (n = 94) were enrolled from the main maternity hospital in Kingston, Jamaica. The LBW infants were randomly assigned to control or intervention comprising weekly home visits from birth to 8 wk and from 7 to 24 mo of age. Development was assessed at 15 and 24 mo with the Griffiths Scales. The intervention benefited the infants' developmental quotient (DQ, P < 0.05) and performance subscale at 15 mo (P < 0.02), the hand and eye (P < 0.05) and performance subscales (P < 0.02) at 24 mo, and home environment at 12 mo. The effect of the intervention on development was mediated in part by the improvement in the home environment. The control LBW infants had significantly lower scores than the NBW in DQ and several subscales, whereas there were no significant differences between the NBW and the LBW infants after intervention. In conclusion, term LBW was associated with developmental delays, which were reduced with psychosocial intervention.

Longitudinal analysis of lymphocyte ratios and HIV-1 intracellular DNA levels in children.

The associations between human immunodeficiency virus type 1 (HIV-1) intracellular DNA and immunological markers were analyzed longitudinally for children with sustained, undetectable RNA levels while receiving highly active antiretroviral therapy (HAART) for >2 years. When DNA levels reached a plateau at week 104 of therapy, in contrast to findings for adults, there was no correlation between the CD4(+) : CD8(+) ratio and DNA levels (r=-0.02; P=.95), and naive CD4(+)CD45RA(+) lymphocytes predominated. These data suggest that the increased proportion of naive lymphocytes found in children are less susceptible to HIV-1 infection than are the memory lymphocytes that dominate immune reconstitution in adults.

A randomized controlled trial of a home-visiting intervention on cognition and behavior in term low birth weight infants.

OBJECTIVES: To determine whether early psychosocial intervention with low birth weight term (LBW-T) infants improved cognition and behavior and to compare LBW-T with normal birth weight (NBW) infants. STUDY DESIGN: A randomized controlled trial was carried out in Kingston, Jamaica, with 140 LBW-T infants (weight<2500 g). The intervention comprised weekly home visits by paraprofessionals for the first 8 weeks of life aimed at improving maternal-child interaction. LBW-T and 94 matched NBW (weight 2500 to 4000 g) infants were recruited from the main maternity hospital. Main outcome measures were problem solving (2 means-end tests: cover and support) and 4 behavior ratings at 7 months. Analyses used were the t test for intervention effects and multiple regression to compare LBW and NBW infants. RESULTS: LBW-T intervened infants had higher scores than LBW-T control infants on the cover test (P<.05) and were more cooperative (P<.01) and happy (P<.05). LBW-T control infants had poorer scores on both the cover (P<.001) and support tests (P<.01), vocalized less (P<.02), and were less cooperative (P<.001), happy (P<.02), and active (P<.02) than NBW infants. LBW-T intervened infants had lower scores than NBW infants only on the support test (P<.05). CONCLUSIONS: Early low-cost intervention can improve cognition and behavior of LBW-T infants in developing countries.

Perceptions and experiences of violence among secondary school students in urban Jamaica.

OBJECTIVE: To obtain information on the perceptions and experiences of violence among secondary school students in Kingston, Jamaica, and its environs. METHODS: Data collection was carried out from September through December 1998. Two researchers administered questionnaires in 11 randomly selected secondary schools, to a total of 1 710 students who were in either grade 7 or grade 9 and who were aged 9-17 years old (mean of 13.2 years). Frequency distributions of the responses were compared by gender, age, grade level, socioeconomic status, and school type. RESULTS: Seventy-five percent of the students thought that someone who was reluctant to fight would be "picked on" more, 89% thought it generally wrong to hit other people, and 91% thought it wrong to insult other people. Eighty-four percent knew of students who carried knives or blades from such items as a scalpel or a utility knife to school, and 89% were worried about violence at school. Thirty-three percent had been victims of violence, and 60% had a family member who had been a victim of violence. Eighty-two percent thought that violent television shows could increase aggressive behavior. Factor analysis of selected responses was carried out, yielding five factors: neighborhood violence, school violence, perceptions of acceptable behaviors, level of concern about violence, and general experiences and perceptions of violence. The factors varied with gender, age, grade level, socioeconomic status, and school type. CONCLUSIONS: These results will help focus interventions aimed at reducing violence, provide a baseline for later comparisons of perceptions and experiences of violence, and offer a basis for comparing the experiences of young people in urban Jamaica with those of young persons elsewhere.

Perceptions and experiences of violence among secondary school students in urban Jamaica

Objective. To obtain information on the perceptions and experiences of violence among secondary school students in Kingston, Jamaica, and its environs. Methods. Data collection was carried out from September through December 1998. Two researchers administered questionnaires in 11 randomly selected secondary schools, to a total of 1,710 students who were in either grade 7 or grade 9 and who were aged 9-17 years old (mean of 13.2 years). Frequency distributions of the responses were compared by gender, age, grade level, socioeconomic status, and school type. Results. Seventy-five percent of the students thought that someone who was reluctant to fight would be "picked on" more, 89 percent thought it generally wrong to hit other people, and 91 percent thought it wrong to insult other people. Eighty-four percent knew of students who carried knives or blades from such items as a scalpel or a utility knife to school, and 89 percent were worried about violence at school. Thirty-three percent had been victims of violence, and 60 percent had a family member who had been a victim of violence. Eighty-two percent thought that violent television shows could increase aggressive behavior. Factor analysis of selected responses was carried out, yielding five factors: neighbourhood violence, school violence, perceptions of acceptable behaviors, level of concern about violence, school violence, and general experiences and perceptions of violence. The factors varied with gender, age, grade level, socioeconomic status, and school type. Conclusions. These results will help focus interventions aimed at reducing violence, provide a baseline for later comparisons of perceptions and experiences of violence, and offer a basis for comparing the experiences of young people in urban Jamaica with those of young persons elsewhere (AU)

Percepciones y experiencias en torno a la violencia en estudiantes de secundaria en la zona urbana de Jamaica

OBJECTIVE: To obtain information on the perceptions and experiences of violence among secondary school students in Kingston, Jamaica, and its environs. METHODS: Data collection was carried out from September through December 1998. Two researchers administered questionnaires in 11 randomly selected secondary schools, to a total of 1 710 students who were in either grade 7 or grade 9 and who were aged 9-17 years old (mean of 13.2 years). Frequency distributions of the responses were compared by gender, age, grade level, socioeconomic status, and school type. RESULTS: Seventy-five percent of the students thought that someone who was reluctant to fight would be "picked on" more, 89 percent thought it generally wrong to hit other people, and 91 percent thought it wrong to insult other people. Eighty-four percent knew of students who carried knives or blades from such items as a scalpel or a utility knife to school, and 89 percent were worried about violence at school. Thirty-three percent had been victims of violence, and 60 percent had a family member who had been a victim of violence. Eighty-two percent thought that violent television shows could increase aggressive behavior. Factor analysis of selected responses was carried out, yielding five factors: neighborhood violence, school violence, perceptions of acceptable behaviors, level of concern about violence, and general experiences and perceptions of violence. The factors varied with gender, age, grade level, socioeconomic status, and school type. CONCLUSIONS: These results will help focus interventions aimed at reducing violence, provide a baseline for later comparisons of perceptions and experiences of violence, and offer a basis for comparing the experiences of young people in urban Jamaica with those of young persons elsewhere.

Persistence of human immunodeficiency virus (HIV) type 1 DNA in peripheral blood despite prolonged suppression of plasma HIV-1 RNA in children.

Human immunodeficiency virus (HIV) type 1 DNA in peripheral blood mononuclear cells (PBMC) was quantified in 31 children who received efavirenz, nelfinavir, and 1 or 2 nucleoside reverse-transcriptase inhibitors for > or =2 years and in whom undetectable plasma HIV-1 RNA levels (< 50 copies/mL) were sustained, to determine the usefulness of HIV-1 DNA as a marker of virus suppression. The median baseline HIV-1 DNA level was 750 copies/10(6) PBMC. After initiation of highly active antiretroviral therapy (HAART), HIV-1 DNA levels decreased gradually, reaching a plateau from week 80 through week 104 (median HIV-1 DNA level, 263 copies/10(6) PBMC). Children who had plasma HIV-1 RNA levels < 50 copies/mL after receiving HAART for 8 weeks (n=16) had persistently lower quantities of intracellular HIV-1 DNA than children whose HIV-1 RNA levels reached < 50 copies/mL after 8 weeks of HAART (n=15). The median half-life for intracellular HIV-1 DNA was 60 weeks. Thus, despite prolonged maintenance of undetectable levels of plasma HIV-1 RNA, HIV-1 DNA remains detectable in PBMC of children and may be a useful marker of further virus suppression.