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AIDS Care: Psychological and Socio-medical Aspects of AIDS/HIV Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/caic20
A systematic review examining whether interventions are effective in reducing cognitive delay in children infected and affected with HIV a
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Lorraine Sherr , Natasha Croome , Katie Bradshaw & Katherine Parra Castaneda a
Department of Infection and Population Health, University College London, Royal Free Hospital, London, UK Published online: 10 Apr 2014.
To cite this article: Lorraine Sherr, Natasha Croome, Katie Bradshaw & Katherine Parra Castaneda (2014) A systematic review examining whether interventions are effective in reducing cognitive delay in children infected and affected with HIV, AIDS Care: Psychological and Socio-medical Aspects of AIDS/HIV, 26:sup1, S70-S77, DOI: 10.1080/09540121.2014.906560 To link to this article: http://dx.doi.org/10.1080/09540121.2014.906560
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AIDS Care, 2014 Vol. 26, No. Supplement 1, 70–77, http://dx.doi.org/10.1080/09540121.2014.906560
A systematic review examining whether interventions are effective in reducing cognitive delay in children infected and affected with HIV Lorraine Sherr*, Natasha Croome, Katie Bradshaw and Katherine Parra Castaneda Department of Infection and Population Health, University College London, Royal Free Hospital, London, UK
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(Received 2 January 2014; accepted 13 March 2014) Cognitive delay has been recorded in children infected and affected by HIV. This finding is well established, yet few countries report provision of special educational interventions for this group of children. The general rehabilitation literature describes an array of effective interventions for children with learning difficulties. These have rarely been adapted for children affected by HIV, despite their growing numbers. A systematic review was conducted to examine effective interventions for cognitive delay in children (under 18 years) infected with HIV and/or exposed to HIV (HIVnegative child born to an HIV-positive mother). A keyword search of electronic databases with reference follow-up generated 1745 hits. These abstracts were screened for relevance, resulting in 17 papers available for shortlisting. Studies were then included if they were randomised control trials, were longitudinal, pre/post or cohort studies and presented empirical data on an intervention for children infected by HIV or exposed to HIV and had at least one cognitive measure. Carer interventions were included if they had at least one child cognitive measure. Of the 17 papers, 4 met the inclusion criteria based on design and quality. Interventions included cognitive rehearsal, home-based stimulation and parental support. All four interventions showed at least one significant child improvement at follow-up. Despite such improvements, many children still scored within the disability range at follow-up. These results show that the effective interventions are available and should be scaled up to meet the needs of children. Complex interventions are not sufficiently studied. This review suggests an ongoing need to build evidence-based interventions, but calls on evidencebased programmes to be initiated for HIV-positive and HIV-affected children.
Keywords: cognitive; development; HIV; AIDS; interventions
Introduction In adults, neurocognitive effects of HIV infection have been well established (Heaton et al., 2010; Simioni et al., 2010), with a grading system categorising different levels known as the HIV-associated neurocognitive disorder (Antinori et al., 2007). Less rigour has been applied to the developing child (Sherr, Mueller, & Varrall, 2009). For adults, the challenge is the loss of cognitive facilities, yet for children, it is the failure to gain them in the first place – a very different issue. Early assault on cognitive development is known in the general literature to affect child development and long-term achievement (Moser, Veale, McAllister, & Archer, 2013; Mwaniki, Atieno, Lawn, & Newton, 2012). HIV can cross the blood–brain barrier and has the potential to affect child cognition with possible developmental delay (Whitehead, Potterton, & Coovadia, 2013). The complex assaults of HIV infection on the family system may also compromise the quality of parenting, stimulation and childhood provision, thereby affecting the developmental environment (Richter et al., 2009). Child cognitive development can be affected by the virus itself, exposure to antiretroviral treatment (Le Doaré, Bland, & Newell, 2012), parental illness, parental mental *Corresponding author. Email: [email protected] © 2014 Taylor & Francis
health state, economic situation (Cluver, Boyes, Orkin, & Sherr, 2013), access to nutrition and early stimulation. HIV infection and AIDS in a parent are often associated with prolonged illness and hospitalisation – especially in the absence of treatment. Depression (Sherr, Clucas, Harding, Sibley, & Catalan, 2011), anxiety (Clucas et al., 2011) and suicidality (Catalan et al., 2011) are associated with HIV infection, and illness can change the living conditions of a family by diverting economic resources, prompting unemployment, triggering family breakdown and causing economic decline (Cluver et al., 2013). It is well documented that children with HIV face numerous challenges (Le Doaré et al., 2012; Sherr et al., 2009) with cognitive delay for some children well established. As these children progress into adulthood, delays may continue or jeopardise future attainment for children who may struggle at school, need special educational input and fail to reach their potential (Malee et al., 2011). In the general child development literature, there are numerous interventions that have been efficacious in improving child performance and remediation (Reichow, Servili, Yasamy, Barbui, & Saxena, 2013). Yet many of these interventions are tailored towards specific conditions which may not apply to HIV-infected or HIV-affected
AIDS Care children, many occur in resource-rich countries and few have been developed or adapted to children facing cognitive delay as a result of HIV infection. This review was set up to examine interventions for cognitive delay for children affected by HIV.
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Method In May 2013, we searched the online databases of MEDLINE, PubMed, PsycINFO and the Cochrane Library database to seek out any studies reporting on interventions for cognitive delay for children infected and affected by HIV. Search terms were entered into search engines with some variation to accommodate different databases. The terms included HIV, AIDS, intervention, child, various forms of child (such as infant, minor, baby and newborn), cognitive functioning, neurocognition or cognitive ability or cognitive impairment, memory or language (see Appendix 1 for full search terms). Inclusion and exclusion criteria Papers were restricted to English language publications and were included if they provided empirical data on interventions for HIV-positive children or HIV-exposed children with at least one cognitive measure. A cognitive measure was defined as a measure scoring any aspect of cognitive functioning such as memory, executive
functioning, language, comprehension and decision-making. Carer interventions were included if there was a child cognitive measure for HIV-positive or HIV-exposed children. Our inclusion criteria included the following study designs: randomised control trials (RCTs) and pre/ post, longitudinal and cohort designs. Qualitative studies, non-primary data, review articles and opinion pieces were also excluded. Studies were confined to children aged 18 years and below (United Nations Children’s Fund [UNICEF] definition of a child) and were excluded if the participants were older than 18 years. After the search, papers were read by a team of three psychologists for confirmation of inclusion. The lead author took responsibility for adjudication in case of non-agreement. The search was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations, which set out design and study characteristics for grading of quality (Centre for Reviews and Dissemination [CRD], 2009). For all included papers, detailed extraction of findings was recorded, listing the full reference, the country of study, population and group details, the intervention used, each study measure, the outcomes, results and effectiveness of interventions. The search (see Figure 1) generated 1745 hits. After excluding duplicates and non-relevant items (books and non-English articles), 1548 remained for more detailed exploration of full title and abstract of which 1531 were
1745 hits
197 duplicates excluded
1548 unique hits to be screened 1531 excluded from abstract screening
17 papers to be reviewed in full-text 14 excluded at full-text screening: .14 No cognitive measures 1 paper found from extra references
4 studies in final set
Figure 1. Systematic review flowchart.
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excluded due to non-relevance or not fitting the inclusion criteria. The remaining 17 papers were read in full. From this phase, 10 were excluded as they did not include at least one cognitive measure (10 were child and 4 were carer interventions). One further potential study was found from following up references. Four published studies met the eligibility criteria for inclusion and were subjected to detailed data abstraction.
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Results The interventions were conducted in three different countries: South Africa, USA and Uganda (see Table 1). Two interventions included only HIV-positive children and controls (Boivin et al., 2010; Potterton, Stewart, Cooper, & Becker, 2009) and two included only HIVexposed children (Boivin et al., 2013; Rotheram-Borus et al., 2006). The age range for children was 1 year up to 16 years; however, only one intervention included adolescents (Boivin et al., 2010). Three studies’ designs were RCTs (Boivin et al., 2010, 2013; Potterton et al., 2009) and one was a longitudinal study (Rotheram-Borus et al., 2006). Boivin et al. (2010) and Potterton et al. (2009) included only perinatally infected children. Apart from this specification, all of the studies looked at general HIV populations and did not focus on any specific problems. Outcome measures The intervention studies included cognitive, behavioural and quality of cognitive stimulation measures. Two studies (Potterton et al., 2009; Rotheram-Borus et al., 2006) included the same cognitive measure: the Bayley Scales of Infant Development (BSID; Bayley, 1969; BSID-II; Bayley, 1993), one (Boivin et al., 2010) used the Cogstate computerised neuropsychological battery (COGSTATE, n.d.) and one (Boivin et al., 2013) included three measures: the Mullen Early Learning Scales (MELS; Mullen, 1995), the Color-Object Association Test (COAT; Jordan, Johnson, Hughes, & Shapiro, 2008) for memory and the Kaufman Assessment Battery for Children (K-ABC; Kaufman & Kaufman, 1983a, 1983b). The BSID assesses children aged 1–42 months on five key developmental domains: cognition, language, socialemotional, motor and adaptive behaviour. The child is evaluated through three scales: Psychomotor Developmental Index (PDI), Mental Developmental Index (MDI) and behaviour (Bayley, 1969, 1993). The Cogstate uses computerised tests to identify and measure cognitive impairment or track cognitive change. The different tests assess visual motor function, executive functioning, processing speed, visual attention, visual learning, verbal learning, attention and social cognition (COGSTATE, n.d.). The MELS assesses cognitive ability and motor development in infants and children from birth to 68
months. The child is measured on five scales: gross motor, visual reception, fine motor, expressive language and receptive language (Mullen, 1995). The COAT measures declarative and immediate memory in infants and young children aged 18–36 months by using placement of toys inside coloured boxes (Jordan et al., 2008). The K-ABC (Kaufman & Kaufman, 1983a, 1983b) measures cognitive ability (using 16 subtests) of children aged 2½ to 12½ years of age. One child and two carer behavioural measures were used in two studies (Boivin et al., 2013; Rotheram-Borus et al., 2006). Two versions of the Child Behaviour Checklist (CBCL) were used; Rotheram-Borus et al. (2006) used the CBCL/2-3 (Achenbach, 1992) and Boivin et al. (2013) used the CBCL/1.5-5 (Achenbach & Rescorla, 2001). The CBCL can be completed by mother or child and assesses internalising and externalising behaviour. The CBCL/2-3 is used for preschool children between ages of 2 and 3 and the CBCL/1.5-5 is used for preschool children from 18 months to 5 years. One measure assessing quality of social and cognitive stimulation was used in two studies (Boivin et al., 2013; Rotheram-Borus et al., 2006); Home Observation for Measurement of the Environment (HOME; Caldwell & Bradley, 1984). The HOME measure includes 46 dichotomous items (yes/no) which consist of seven subscales: availability of learning materials, language stimulation, appropriate physical environment, caretaker responsivity, academic stimulation, parental behavioural modelling and variety in activity and environment. The yes items are summed for each subscale and a higher score indicates a more stimulating environment (Rotheram-Borus et al., 2006). Interventions The four interventions included a coping skills intervention, basic home-stimulation intervention, Computerised Cognitive Rehabilitation Therapy (CCRT; Sandford, 2007) and a Mediational Intervention for Sensitising Caregivers (MISC; Klein, 1996). Rotheram-Borus, Lee, Gwadz, and Draimin (2001) conducted a family-based, coping skills intervention with parents living with HIV (PWH) and their adolescent children. The included study (Rotheram-Borus et al., 2006) examined the longitudinal effect of the family intervention on the grandchildren of the PWH by assessing the children (experimental M = 15.5 months, SD = 2.4; control M = 14.6 months, SD = 1.7) at 12, 24 and/or 36 months. The PWH (aged between 25 and 70) and their adolescent children (11–18 years old) were recruited from AIDS Services in New York, USA, contingent upon adolescent disclosure of parental HIV status. Families were randomly assigned to the intervention plus standard care (153 PWH; 205 adolescents) or the
Table 1. Summary of intervention studies aimed at improving cognitive performance of HIV-infected and affected children.
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Study RotheramBorus et al. (2006)
Sample size Intervention condition (153 PWH, 212 adolescents), control condition (154 PWH, 211 adolescents)
Comparison group HIV+ receiving intervention versus HIV + controls
Measures
Results
Coping skills intervention
CBCL
Intervention condition was found to have:significantly fewer symptoms overall across time on the CBCL; t(25) =3.13, β = 7.3449, p = .004; fewer internalising symptoms across time; t(25) = 2.72, β = 5.8095, p = .012; fewer externalising symptoms at 3 years; t(24) = 4.05, β = 10.0798, p = .001.
BSID
Grandchildren in the intervention condition tended to have better MDI scores at each assessment window (12, 24 and 36 months) than the grandchildren in the control condition: t(52) = 1.77, β = 4.3712, p = .083. Grandchildren in the control condition tended to have lower mean HOME scores compared with the intervention condition across time, t(53) = −1.95, β = 2.7761, p = .056. Children in the experimental group showed significantly greater improvement in cognitive (p = .010) and motor (p = .020) development over time than children in the comparison group. MDI: The degree of changeover the year was significantly greater (p = .01) in the experimental group (from MDI 62.6 to 69.3) than in the comparison group (from MDI 68.5 to 64.3). PDI: The degree of improvement over time was significantly greater (p = .02) in the experimental group (from PDI 49.8 to 70.5) than in the comparison group (from PDI 57.4 to 65.9). Despite the improvement for the experimental group, the mean MDI and PDI scores at the end of the study period indicated that the children’s cognitive and motor development was still significantly delayed. Highly significant intervention effects were found for:Maze learning (group effect = −0.06, SE = 0.02, p < .001) Card detection speed (group effect 0.06, SE = 0.02, p < .02). The MISC children showed greater gains than the controls over time on the MELS scales of: receptive language (p = .004), expressive language (p =.001) and composite score of overall cognitive ability (p = .006).
HOME
Potterton et al. (2009)
122 HIV+ children (60 experimental, 62 control)
HIV+ receiving intervention versus HIV+ controls
Basic homestimulation programme
Boivin et al. (2010)
60 HIV+ children
HIV+ receiving intervention versus HIVpositive controls
CCRT
Boivin et al. (2013)
119 HIV-exposed children and their caregivers
Treatment 1 biweekly MISC training alternating between home and clinic for one year versus
MISC
BSID
Cogstate computerised neuropsychological battery MELS
Effective? (Y/N) Y
Y
Y
Y
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Intervention
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Sample size Study
Table 1. (Continued)
Hopkins Symptoms Checklist-25 for depression and anxiety (HSCL)
COAT for memory Achenbach CBCL HOME Treatment 2 (a health and nutrition curriculum)
Comparison group
Intervention
Measures
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Results
No differences between groups No significant differences HOME score significantly improved for the experimental group compared to the control group (p < .0001) Caregiver HSCL anxiety was significantly predictive of the child’s CBCL: internalising symptoms (p < .0001; e.g., anxiety, depression and somatic complaint) and CBCL total symptoms (p = .003).
Effective? (Y/N)
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control condition with standard care only (154 PWH; 207 adolescents). The intervention was a group-based series of two modules, based on social learning principles. The first module (4 half days) aimed at parents addressed coping with the illness and disclosure. The second module (8 half days) included both parents and adolescents (separately) and covered topics such as sharing emotions, listening, problem-solving, practising safe sex and setting future goals. The PWH and the adolescents, in the intervention condition, reported significantly lower levels of emotional distress and problem behaviours. Adolescents also reported lower conduct problems, family-related stressors and higher levels of self-esteem than the control group. For PWH, coping style, levels of disclosure and formation of legal custody plans were similar across the two groups (Rotheram-Borus et al., 2006). Long-term follow-up of the infants of the adolescents in the study several years later showed developmental advantage for the children of the intervention group compared to those in the control group with a trend for higher scores on the MDI (Bayley, 1969; p = .08), significantly fewer behavioural symptoms and internalising symptoms across time as well as having fewer externalising symptoms at 36 months. Using the HOME measure, there were no significant differences between the two groups. Potterton et al. (2009) conducted a RCT with 122 HIV-positive children (vertically transmitted) aged less than 2 years 6 months recruited from a Children’s Clinic in Soweto, South Africa. The participants were randomly assigned to either the experimental group (M = 18 months, SD = 8.1) who were given a home-stimulation intervention as well as normal clinic care or the control group (M = 19.01 months, SD = 8.2) who received normal clinic care with no extra stimulation. Child cognitive and developmental ability was assessed by a blinded researcher at baseline, 6 months and 12 months. The intervention programme was structured around developmentally appropriate play and daily living exercises integrated into daily living activities. Potterton et al. (2009) found at baseline the MDI and the PDI scores were low and were not significantly different between the experimental and the control groups. The degree of change on the MDI and PDI was significantly greater for the experimental group (MDI = 62.6–69.3; PDI = 49.8– 70.5) than the control group (MDI = 68.5–64.3; PDI = 57.4–65.9). Despite this, measures after the intervention still showed both groups to be exhibiting scores indicating delay for both cognitive and motor measures. Boivin et al. (2010) tested a 10-session (5 weeks) computerised cognitive rehearsal intervention in a sample of 60 perinatally infected HIV-positive Ugandan children (23 on antiretroviral therapy [ART]) aged between 6 and 16, with 32 randomly assigned to the intervention (M = 9.32 years, SD = 2.61) and 28 assigned to the control group with no intervention (M =
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AIDS Care 10.34 years, SD = 3.01). The researchers chose 15 exercises from the CCRT 35 multi-level brain training exercises to help develop cognitive skills (4 attention, 4 conceptual/memory, 3 visual motor and 4 logic domain exercises). Cognitive ability was assessed with two measures at baseline (K-ABC, Cogstate) and one postintervention measure (Cogstate). Boivin et al. (2010) found there were no significant differences on cognitive ability between the experimental and the control groups on the K-ABC; however, children in the CCRT group had significantly higher scores on the Cogstate: one-care learning exercise. Post-intervention, the experimental group performed significantly better on the Cogstate Groton maze learning exercise (M = 0.06, SE = 0.06) than the control group (M = 0.13, SE = 0.11). The experimental participants were also significantly faster on the card detection exercise (M = 2.85, SE = 0.12) than the control group (M = 2.78, SE = 0.08). There were trends for the experimental group to perform better on the Groton maze chasing (p = .08) and the working memory task (0.06); however, these were not significant. In a later study, Boivin et al. (2013) completed a year-long MISC intervention to try and enhance HIVexposed children’s cognitive and emotional development in Uganda. One hundred and nineteen children (aged between 2 and 4) and their carers were randomly assigned to the experimental condition (M = 2.8 years, SD = 0.35) who had biweekly MISC training or the comparison group (M = 2.8 years, SD = 0.33) who received health and nutrition training. The MISC training provided carers with strategies to enhance their children’s development through daily interactions. The biweekly hour training alternated between being conducted at home (where the MISC trainers could observe and direct the interactions between child and carer) and being conducted at the office (videotapes of interactions were used for training). All children and carers were assessed at baseline, six months and one year. The study found no significant differences between the intervention and the comparison groups at baseline. Using the MELS, the intervention children showed greater improvement over time on receptive language, expressive language and cognitive composite scores. There were no differences between the groups for immediate recall using the COAT measure but there was a trend for the intervention group to improve more than the comparison group on the total recall score (p = .054). There were no significant differences for groups by time on internalising, externalising and total behaviour problems. Gender All four studies provided data on child gender; however, only one (Boivin et al., 2013) analysed by gender. No significant differences were found.
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Discussion This systematic review highlights the challenges of cognitive development in an era of HIV infection, and shows the emerging database on effective interventions available to improve cognitive performance. The studies also utilise different measures, making meta-analysis impossible. An agreed consensus on measurement may be a useful coordinating mechanism to improve the database. All four interventions show a significant improvement in children’s cognitive and motor development, whether the intervention is directed at the child or at the family/caregiver. The approaches are different with cognitive rehearsal and individual as well as group support. It is unclear if these can be adjusted to lower cost, lower skill and lower intensity for general implementation. They hold out promise for remedial programmes to be scaled up for children with HIV infection. No data exists on complex interventions or combined approaches. The domains with established effective improvement include memory, attention, behavioural parameters, emotional functioning and motor and psychomotor measures. This study does have some limitations. The lack of published evidence does not necessarily reflect the lack of interventions being implemented. Also the inclusion criteria only included articles in English and published literature. There may be relevant data in grey literature and in other languages. The current data clearly describe cognitive delay in HIV-infected and HIV-exposed children. Cognitive delay can be caused by biological factors, environmental factors or both. The trajectory of HIV infection in the family exposes children not only to HIV, ART treatment, but also to ongoing stress and trauma. All of which may affect cognitive performance. The intervention data show potential and suggest that special education interventions are both needed and available. These results should be integrated into programmes and policy as a matter of urgency, to ensure that all children infected and affected by HIV can maximise their potential and benefit from support. References Achenbach, T. M. (1992). Manual for child behaviour checklist/2–3 and 1992 profile. Burlington: Department of Psychiatry, University of Vermont. Achenbach, T. M., & Rescorla, L. A. (2001). Manual for the ASEBA school-age forms & profiles: An integrated system of multi-informant assessment. Burlington: Research Center for Children, Youth, & Families, University of Vermont. Antinori, A., Arendt, G., Becker, J. T., Brew, B. J., Byrd, D. A., Cherner, M., … Wojna, V. E. (2007). Updated research nosology for HIV-associated neurocognitive disorders. Neurology, 69, 1789–1799. doi:10.1212/01.WNL.000028 7431.88658.8b
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Kaufman, A. S., & Kaufman, N. L. (1983b). Kaufman assessment battery for children: Interpretive manual. Circle Pines, MN: American Guidance Services. Klein, P. S. (1996). Early intervention: Cross-cultural experiences with a mediational approach. New York, NY: Garland. Le Doaré, K., Bland, R., & Newell, M. L. (2012). Neurodevelopment in children born to HIV-infected mothers by infection and treatment status. Pediatrics, 130(5), e1326– e1344. doi:10.1542/peds.2012-0405 Malee, K. M., Tassiopoulos, K., Huo, Y., Siberry, G., Williams, P. L., Hazra R, … Mellins, C. A. (2011). Pediatric HIV/ AIDS cohort study team. Mental health functioning among children and adolescents with perinatal HIV infection and perinatal HIV exposure. AIDS Care, 23, 1533–1544. doi:10.1080/09540121.2011.575120 Moser, J. J., Veale, P. M., McAllister, D. L., & Archer, D. P. (2013). A systematic review and quantitative analysis of neurocognitive outcomes in children with four chronic illnesses. Paediatric Anaesthesia, 23, 1084–1096. doi:10.1111/pan.12255 Mullen, E. M. (1995). Mullen scales of early learning: AGS edition. Minneapolis, MN: American Guidance Services. Mwaniki, M. K., Atieno, M., Lawn, J. E., & Newton, C. R. (2012). Long-term neurodevelopmental outcomes after intrauterine and neonatal insults: A systematic review. Lancet, 379, 445–452. doi:10.1016/S0140-6736(11) 61577-8 Potterton, J., Stewart, A., Cooper, P., & Becker, P. (2009). The effect of a basic home stimulation programme on the development of young children infected with HIV. Developmental Medicine & Child Neurology, 52, 547–551. doi:10.1111/j.1469-8749.2009.03534.x Reichow, B., Servili, C., Yasamy, M. T., Barbui, C., & Saxena, S. (2013). Non-specialist psychosocial interventions for children and adolescents with intellectual disability or lower-functioning autism spectrum disorders: A systematic review. PLoS Medicine, 10(12), e1001572. doi:10.1371/journal.pmed.1001572 Richter, L. M., Sherr, L., Adato, M., Belsey, M., Chandan, U., Desmond, C., … Wakhweya, A. (2009). Strengthening families to support children affected by HIV and AIDS. AIDS Care, 21, 3–12. doi:10.1080/09540120902923121 Rotheram-Borus, M. J., Lee, M. B., Gwadz, M., & Draimin, B. (2001). An intervention for parents with AIDS and their adolescent children. American Journal of Public Health, 91, 1294–1302. doi:10.2105/AJPH.91.8.1294 Rotheram-Borus, M. J., Lester, P., Song, J., Lin, Y.-Y., Leonard, N. R., Beckwith, L., … Lord, L. (2006). Intergenerational benefits of family-based HIV interventions. Journal of Consulting and Clinical Psychology, 74, 622–627. doi:10.1037/0022-006X.74.3.622 Sandford, J. A. (2007). Captain’s log computerized cognitive training system. Richmond, VA: Brain Train. Sherr, L., Clucas, C., Harding, R., Sibley, E., & Catalan, J.& Catalan, J. (2011). HIV and depression – A systematic review of interventions. Psychology, Health & Medicine, 16(5), 493–527. doi:10.1080/13548506.2011.579990 Sherr, L., Mueller, J., & Varrall, R. (2009). A systematic review of cognitive development and child human immunodefi-
AIDS Care ciency virus infection. Psychology, Health & Medicine, 14, 387–404. doi:10.1080/13548500903012897 Simioni, S., Cavassini, M., Annoni, J. M., Rimbault Abraham, A., Bourquin, I., Schiffer, V., … Du Pasquier, R. A. (2010). Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS, 24(9), 1243–1250.
Appendix 1 Figure 1. Search strategies.
PsycINFO search
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(1)
(2)
(3) (4) (5)
(6)
(7)
(8)
(9) (10)
(11) (12) (13)
(adolescent or child or minor or infant or preteen or baby or new born or neonate).mp. [mp = title, abstract, heading word, table of contents, key concepts, original title, tests & measures] (360790) (HIV or human immunodeficiency virus or acquired immunodeficiency syndrome).mp. [mp = title, abstract, heading word, table of contents, key concepts, original title, tests & measures] (33882) Exp HIV/ (29459) 2 or 3 (37198) exp Cognitive Ability/ or exp Neurocognition/ or exp Cognitive Impairment/ or Neurocognitive.mp. or exp Cognitive Development/ (128384) (neurodevelopment* or cognitive development).mp. [mp = title, abstract, heading word, table of contents, key concepts, original title, tests & measures] (33883) (cognitive performance or cognitive functioning). mp. [mp = title, abstract, heading word, table of contents, key concepts, original title, tests & measures] (16639) (memory or language or IQ or spatial awareness or social).mp. [mp = title, abstract, heading word, table of contents, key concepts, original title, tests & measures] (878406) 5 or 6 or 7 or 8 (951766) intervention*.mp. or exp Response to Intervention/ or exp Group Intervention/ or exp Family Intervention/ or exp School-Based Intervention/ or exp Early Intervention/ or exp Intervention/ (219966) exp Rehabilitation/ (55735) 10 or 11 (265129) 1 and 4 and 9 and 12 (442)
MEDLINE search (1)
(adolescent or child or minor or infant or preteen or baby or new born or neonate).mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier] (3010294)
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Whitehead, N., Potterton, J., & Coovadia, A. (2013). The neurodevelopment of HIV-infected infants on HAART compared to HIV-exposed but uninfected infants. AIDS Care, 26, 479–504.
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Child/ (1315568) Infant/ (617618) Adolescent/ (1542458) 1 or 2 or 3 or 4 (3010294) (HIV or human immunodeficiency virus or acquired immunodeficiency syndrome).mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier] (258323) HIV Infections/ (136191) 6 or 7 (258323) Neurocognitive.mp. (8099) (neurodevelopment* or cognitive development).mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier] (16088) (cognitive performance or cognitive functioning). mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier] (14752) (memory or language or IQ or spatial awareness or social).mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier] (744204) 9 or 10 or 11 or 12 (767473) Intervention Studies/ or intervention*.mp. (523134) Rehabilitation/ (16328) 14 or 15 (538777) 5 and 8 and 13 and 16 (1303)
AIDS Care: Psychological and Socio-medical Aspects of AIDS/HIV Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/caic20
A systematic review examining whether interventions are effective in reducing cognitive delay in children infected and affected with HIV a
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Lorraine Sherr , Natasha Croome , Katie Bradshaw & Katherine Parra Castaneda a
Department of Infection and Population Health, University College London, Royal Free Hospital, London, UK Published online: 10 Apr 2014.
To cite this article: Lorraine Sherr, Natasha Croome, Katie Bradshaw & Katherine Parra Castaneda (2014) A systematic review examining whether interventions are effective in reducing cognitive delay in children infected and affected with HIV, AIDS Care: Psychological and Socio-medical Aspects of AIDS/HIV, 26:sup1, S70-S77, DOI: 10.1080/09540121.2014.906560 To link to this article: http://dx.doi.org/10.1080/09540121.2014.906560
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AIDS Care, 2014 Vol. 26, No. Supplement 1, 70–77, http://dx.doi.org/10.1080/09540121.2014.906560
A systematic review examining whether interventions are effective in reducing cognitive delay in children infected and affected with HIV Lorraine Sherr*, Natasha Croome, Katie Bradshaw and Katherine Parra Castaneda Department of Infection and Population Health, University College London, Royal Free Hospital, London, UK
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(Received 2 January 2014; accepted 13 March 2014) Cognitive delay has been recorded in children infected and affected by HIV. This finding is well established, yet few countries report provision of special educational interventions for this group of children. The general rehabilitation literature describes an array of effective interventions for children with learning difficulties. These have rarely been adapted for children affected by HIV, despite their growing numbers. A systematic review was conducted to examine effective interventions for cognitive delay in children (under 18 years) infected with HIV and/or exposed to HIV (HIVnegative child born to an HIV-positive mother). A keyword search of electronic databases with reference follow-up generated 1745 hits. These abstracts were screened for relevance, resulting in 17 papers available for shortlisting. Studies were then included if they were randomised control trials, were longitudinal, pre/post or cohort studies and presented empirical data on an intervention for children infected by HIV or exposed to HIV and had at least one cognitive measure. Carer interventions were included if they had at least one child cognitive measure. Of the 17 papers, 4 met the inclusion criteria based on design and quality. Interventions included cognitive rehearsal, home-based stimulation and parental support. All four interventions showed at least one significant child improvement at follow-up. Despite such improvements, many children still scored within the disability range at follow-up. These results show that the effective interventions are available and should be scaled up to meet the needs of children. Complex interventions are not sufficiently studied. This review suggests an ongoing need to build evidence-based interventions, but calls on evidencebased programmes to be initiated for HIV-positive and HIV-affected children.
Keywords: cognitive; development; HIV; AIDS; interventions
Introduction In adults, neurocognitive effects of HIV infection have been well established (Heaton et al., 2010; Simioni et al., 2010), with a grading system categorising different levels known as the HIV-associated neurocognitive disorder (Antinori et al., 2007). Less rigour has been applied to the developing child (Sherr, Mueller, & Varrall, 2009). For adults, the challenge is the loss of cognitive facilities, yet for children, it is the failure to gain them in the first place – a very different issue. Early assault on cognitive development is known in the general literature to affect child development and long-term achievement (Moser, Veale, McAllister, & Archer, 2013; Mwaniki, Atieno, Lawn, & Newton, 2012). HIV can cross the blood–brain barrier and has the potential to affect child cognition with possible developmental delay (Whitehead, Potterton, & Coovadia, 2013). The complex assaults of HIV infection on the family system may also compromise the quality of parenting, stimulation and childhood provision, thereby affecting the developmental environment (Richter et al., 2009). Child cognitive development can be affected by the virus itself, exposure to antiretroviral treatment (Le Doaré, Bland, & Newell, 2012), parental illness, parental mental *Corresponding author. Email: [email protected] © 2014 Taylor & Francis
health state, economic situation (Cluver, Boyes, Orkin, & Sherr, 2013), access to nutrition and early stimulation. HIV infection and AIDS in a parent are often associated with prolonged illness and hospitalisation – especially in the absence of treatment. Depression (Sherr, Clucas, Harding, Sibley, & Catalan, 2011), anxiety (Clucas et al., 2011) and suicidality (Catalan et al., 2011) are associated with HIV infection, and illness can change the living conditions of a family by diverting economic resources, prompting unemployment, triggering family breakdown and causing economic decline (Cluver et al., 2013). It is well documented that children with HIV face numerous challenges (Le Doaré et al., 2012; Sherr et al., 2009) with cognitive delay for some children well established. As these children progress into adulthood, delays may continue or jeopardise future attainment for children who may struggle at school, need special educational input and fail to reach their potential (Malee et al., 2011). In the general child development literature, there are numerous interventions that have been efficacious in improving child performance and remediation (Reichow, Servili, Yasamy, Barbui, & Saxena, 2013). Yet many of these interventions are tailored towards specific conditions which may not apply to HIV-infected or HIV-affected
AIDS Care children, many occur in resource-rich countries and few have been developed or adapted to children facing cognitive delay as a result of HIV infection. This review was set up to examine interventions for cognitive delay for children affected by HIV.
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Method In May 2013, we searched the online databases of MEDLINE, PubMed, PsycINFO and the Cochrane Library database to seek out any studies reporting on interventions for cognitive delay for children infected and affected by HIV. Search terms were entered into search engines with some variation to accommodate different databases. The terms included HIV, AIDS, intervention, child, various forms of child (such as infant, minor, baby and newborn), cognitive functioning, neurocognition or cognitive ability or cognitive impairment, memory or language (see Appendix 1 for full search terms). Inclusion and exclusion criteria Papers were restricted to English language publications and were included if they provided empirical data on interventions for HIV-positive children or HIV-exposed children with at least one cognitive measure. A cognitive measure was defined as a measure scoring any aspect of cognitive functioning such as memory, executive
functioning, language, comprehension and decision-making. Carer interventions were included if there was a child cognitive measure for HIV-positive or HIV-exposed children. Our inclusion criteria included the following study designs: randomised control trials (RCTs) and pre/ post, longitudinal and cohort designs. Qualitative studies, non-primary data, review articles and opinion pieces were also excluded. Studies were confined to children aged 18 years and below (United Nations Children’s Fund [UNICEF] definition of a child) and were excluded if the participants were older than 18 years. After the search, papers were read by a team of three psychologists for confirmation of inclusion. The lead author took responsibility for adjudication in case of non-agreement. The search was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations, which set out design and study characteristics for grading of quality (Centre for Reviews and Dissemination [CRD], 2009). For all included papers, detailed extraction of findings was recorded, listing the full reference, the country of study, population and group details, the intervention used, each study measure, the outcomes, results and effectiveness of interventions. The search (see Figure 1) generated 1745 hits. After excluding duplicates and non-relevant items (books and non-English articles), 1548 remained for more detailed exploration of full title and abstract of which 1531 were
1745 hits
197 duplicates excluded
1548 unique hits to be screened 1531 excluded from abstract screening
17 papers to be reviewed in full-text 14 excluded at full-text screening: .14 No cognitive measures 1 paper found from extra references
4 studies in final set
Figure 1. Systematic review flowchart.
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excluded due to non-relevance or not fitting the inclusion criteria. The remaining 17 papers were read in full. From this phase, 10 were excluded as they did not include at least one cognitive measure (10 were child and 4 were carer interventions). One further potential study was found from following up references. Four published studies met the eligibility criteria for inclusion and were subjected to detailed data abstraction.
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Results The interventions were conducted in three different countries: South Africa, USA and Uganda (see Table 1). Two interventions included only HIV-positive children and controls (Boivin et al., 2010; Potterton, Stewart, Cooper, & Becker, 2009) and two included only HIVexposed children (Boivin et al., 2013; Rotheram-Borus et al., 2006). The age range for children was 1 year up to 16 years; however, only one intervention included adolescents (Boivin et al., 2010). Three studies’ designs were RCTs (Boivin et al., 2010, 2013; Potterton et al., 2009) and one was a longitudinal study (Rotheram-Borus et al., 2006). Boivin et al. (2010) and Potterton et al. (2009) included only perinatally infected children. Apart from this specification, all of the studies looked at general HIV populations and did not focus on any specific problems. Outcome measures The intervention studies included cognitive, behavioural and quality of cognitive stimulation measures. Two studies (Potterton et al., 2009; Rotheram-Borus et al., 2006) included the same cognitive measure: the Bayley Scales of Infant Development (BSID; Bayley, 1969; BSID-II; Bayley, 1993), one (Boivin et al., 2010) used the Cogstate computerised neuropsychological battery (COGSTATE, n.d.) and one (Boivin et al., 2013) included three measures: the Mullen Early Learning Scales (MELS; Mullen, 1995), the Color-Object Association Test (COAT; Jordan, Johnson, Hughes, & Shapiro, 2008) for memory and the Kaufman Assessment Battery for Children (K-ABC; Kaufman & Kaufman, 1983a, 1983b). The BSID assesses children aged 1–42 months on five key developmental domains: cognition, language, socialemotional, motor and adaptive behaviour. The child is evaluated through three scales: Psychomotor Developmental Index (PDI), Mental Developmental Index (MDI) and behaviour (Bayley, 1969, 1993). The Cogstate uses computerised tests to identify and measure cognitive impairment or track cognitive change. The different tests assess visual motor function, executive functioning, processing speed, visual attention, visual learning, verbal learning, attention and social cognition (COGSTATE, n.d.). The MELS assesses cognitive ability and motor development in infants and children from birth to 68
months. The child is measured on five scales: gross motor, visual reception, fine motor, expressive language and receptive language (Mullen, 1995). The COAT measures declarative and immediate memory in infants and young children aged 18–36 months by using placement of toys inside coloured boxes (Jordan et al., 2008). The K-ABC (Kaufman & Kaufman, 1983a, 1983b) measures cognitive ability (using 16 subtests) of children aged 2½ to 12½ years of age. One child and two carer behavioural measures were used in two studies (Boivin et al., 2013; Rotheram-Borus et al., 2006). Two versions of the Child Behaviour Checklist (CBCL) were used; Rotheram-Borus et al. (2006) used the CBCL/2-3 (Achenbach, 1992) and Boivin et al. (2013) used the CBCL/1.5-5 (Achenbach & Rescorla, 2001). The CBCL can be completed by mother or child and assesses internalising and externalising behaviour. The CBCL/2-3 is used for preschool children between ages of 2 and 3 and the CBCL/1.5-5 is used for preschool children from 18 months to 5 years. One measure assessing quality of social and cognitive stimulation was used in two studies (Boivin et al., 2013; Rotheram-Borus et al., 2006); Home Observation for Measurement of the Environment (HOME; Caldwell & Bradley, 1984). The HOME measure includes 46 dichotomous items (yes/no) which consist of seven subscales: availability of learning materials, language stimulation, appropriate physical environment, caretaker responsivity, academic stimulation, parental behavioural modelling and variety in activity and environment. The yes items are summed for each subscale and a higher score indicates a more stimulating environment (Rotheram-Borus et al., 2006). Interventions The four interventions included a coping skills intervention, basic home-stimulation intervention, Computerised Cognitive Rehabilitation Therapy (CCRT; Sandford, 2007) and a Mediational Intervention for Sensitising Caregivers (MISC; Klein, 1996). Rotheram-Borus, Lee, Gwadz, and Draimin (2001) conducted a family-based, coping skills intervention with parents living with HIV (PWH) and their adolescent children. The included study (Rotheram-Borus et al., 2006) examined the longitudinal effect of the family intervention on the grandchildren of the PWH by assessing the children (experimental M = 15.5 months, SD = 2.4; control M = 14.6 months, SD = 1.7) at 12, 24 and/or 36 months. The PWH (aged between 25 and 70) and their adolescent children (11–18 years old) were recruited from AIDS Services in New York, USA, contingent upon adolescent disclosure of parental HIV status. Families were randomly assigned to the intervention plus standard care (153 PWH; 205 adolescents) or the
Table 1. Summary of intervention studies aimed at improving cognitive performance of HIV-infected and affected children.
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Study RotheramBorus et al. (2006)
Sample size Intervention condition (153 PWH, 212 adolescents), control condition (154 PWH, 211 adolescents)
Comparison group HIV+ receiving intervention versus HIV + controls
Measures
Results
Coping skills intervention
CBCL
Intervention condition was found to have:significantly fewer symptoms overall across time on the CBCL; t(25) =3.13, β = 7.3449, p = .004; fewer internalising symptoms across time; t(25) = 2.72, β = 5.8095, p = .012; fewer externalising symptoms at 3 years; t(24) = 4.05, β = 10.0798, p = .001.
BSID
Grandchildren in the intervention condition tended to have better MDI scores at each assessment window (12, 24 and 36 months) than the grandchildren in the control condition: t(52) = 1.77, β = 4.3712, p = .083. Grandchildren in the control condition tended to have lower mean HOME scores compared with the intervention condition across time, t(53) = −1.95, β = 2.7761, p = .056. Children in the experimental group showed significantly greater improvement in cognitive (p = .010) and motor (p = .020) development over time than children in the comparison group. MDI: The degree of changeover the year was significantly greater (p = .01) in the experimental group (from MDI 62.6 to 69.3) than in the comparison group (from MDI 68.5 to 64.3). PDI: The degree of improvement over time was significantly greater (p = .02) in the experimental group (from PDI 49.8 to 70.5) than in the comparison group (from PDI 57.4 to 65.9). Despite the improvement for the experimental group, the mean MDI and PDI scores at the end of the study period indicated that the children’s cognitive and motor development was still significantly delayed. Highly significant intervention effects were found for:Maze learning (group effect = −0.06, SE = 0.02, p < .001) Card detection speed (group effect 0.06, SE = 0.02, p < .02). The MISC children showed greater gains than the controls over time on the MELS scales of: receptive language (p = .004), expressive language (p =.001) and composite score of overall cognitive ability (p = .006).
HOME
Potterton et al. (2009)
122 HIV+ children (60 experimental, 62 control)
HIV+ receiving intervention versus HIV+ controls
Basic homestimulation programme
Boivin et al. (2010)
60 HIV+ children
HIV+ receiving intervention versus HIVpositive controls
CCRT
Boivin et al. (2013)
119 HIV-exposed children and their caregivers
Treatment 1 biweekly MISC training alternating between home and clinic for one year versus
MISC
BSID
Cogstate computerised neuropsychological battery MELS
Effective? (Y/N) Y
Y
Y
Y
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Intervention
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Sample size Study
Table 1. (Continued)
Hopkins Symptoms Checklist-25 for depression and anxiety (HSCL)
COAT for memory Achenbach CBCL HOME Treatment 2 (a health and nutrition curriculum)
Comparison group
Intervention
Measures
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Results
No differences between groups No significant differences HOME score significantly improved for the experimental group compared to the control group (p < .0001) Caregiver HSCL anxiety was significantly predictive of the child’s CBCL: internalising symptoms (p < .0001; e.g., anxiety, depression and somatic complaint) and CBCL total symptoms (p = .003).
Effective? (Y/N)
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control condition with standard care only (154 PWH; 207 adolescents). The intervention was a group-based series of two modules, based on social learning principles. The first module (4 half days) aimed at parents addressed coping with the illness and disclosure. The second module (8 half days) included both parents and adolescents (separately) and covered topics such as sharing emotions, listening, problem-solving, practising safe sex and setting future goals. The PWH and the adolescents, in the intervention condition, reported significantly lower levels of emotional distress and problem behaviours. Adolescents also reported lower conduct problems, family-related stressors and higher levels of self-esteem than the control group. For PWH, coping style, levels of disclosure and formation of legal custody plans were similar across the two groups (Rotheram-Borus et al., 2006). Long-term follow-up of the infants of the adolescents in the study several years later showed developmental advantage for the children of the intervention group compared to those in the control group with a trend for higher scores on the MDI (Bayley, 1969; p = .08), significantly fewer behavioural symptoms and internalising symptoms across time as well as having fewer externalising symptoms at 36 months. Using the HOME measure, there were no significant differences between the two groups. Potterton et al. (2009) conducted a RCT with 122 HIV-positive children (vertically transmitted) aged less than 2 years 6 months recruited from a Children’s Clinic in Soweto, South Africa. The participants were randomly assigned to either the experimental group (M = 18 months, SD = 8.1) who were given a home-stimulation intervention as well as normal clinic care or the control group (M = 19.01 months, SD = 8.2) who received normal clinic care with no extra stimulation. Child cognitive and developmental ability was assessed by a blinded researcher at baseline, 6 months and 12 months. The intervention programme was structured around developmentally appropriate play and daily living exercises integrated into daily living activities. Potterton et al. (2009) found at baseline the MDI and the PDI scores were low and were not significantly different between the experimental and the control groups. The degree of change on the MDI and PDI was significantly greater for the experimental group (MDI = 62.6–69.3; PDI = 49.8– 70.5) than the control group (MDI = 68.5–64.3; PDI = 57.4–65.9). Despite this, measures after the intervention still showed both groups to be exhibiting scores indicating delay for both cognitive and motor measures. Boivin et al. (2010) tested a 10-session (5 weeks) computerised cognitive rehearsal intervention in a sample of 60 perinatally infected HIV-positive Ugandan children (23 on antiretroviral therapy [ART]) aged between 6 and 16, with 32 randomly assigned to the intervention (M = 9.32 years, SD = 2.61) and 28 assigned to the control group with no intervention (M =
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AIDS Care 10.34 years, SD = 3.01). The researchers chose 15 exercises from the CCRT 35 multi-level brain training exercises to help develop cognitive skills (4 attention, 4 conceptual/memory, 3 visual motor and 4 logic domain exercises). Cognitive ability was assessed with two measures at baseline (K-ABC, Cogstate) and one postintervention measure (Cogstate). Boivin et al. (2010) found there were no significant differences on cognitive ability between the experimental and the control groups on the K-ABC; however, children in the CCRT group had significantly higher scores on the Cogstate: one-care learning exercise. Post-intervention, the experimental group performed significantly better on the Cogstate Groton maze learning exercise (M = 0.06, SE = 0.06) than the control group (M = 0.13, SE = 0.11). The experimental participants were also significantly faster on the card detection exercise (M = 2.85, SE = 0.12) than the control group (M = 2.78, SE = 0.08). There were trends for the experimental group to perform better on the Groton maze chasing (p = .08) and the working memory task (0.06); however, these were not significant. In a later study, Boivin et al. (2013) completed a year-long MISC intervention to try and enhance HIVexposed children’s cognitive and emotional development in Uganda. One hundred and nineteen children (aged between 2 and 4) and their carers were randomly assigned to the experimental condition (M = 2.8 years, SD = 0.35) who had biweekly MISC training or the comparison group (M = 2.8 years, SD = 0.33) who received health and nutrition training. The MISC training provided carers with strategies to enhance their children’s development through daily interactions. The biweekly hour training alternated between being conducted at home (where the MISC trainers could observe and direct the interactions between child and carer) and being conducted at the office (videotapes of interactions were used for training). All children and carers were assessed at baseline, six months and one year. The study found no significant differences between the intervention and the comparison groups at baseline. Using the MELS, the intervention children showed greater improvement over time on receptive language, expressive language and cognitive composite scores. There were no differences between the groups for immediate recall using the COAT measure but there was a trend for the intervention group to improve more than the comparison group on the total recall score (p = .054). There were no significant differences for groups by time on internalising, externalising and total behaviour problems. Gender All four studies provided data on child gender; however, only one (Boivin et al., 2013) analysed by gender. No significant differences were found.
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Discussion This systematic review highlights the challenges of cognitive development in an era of HIV infection, and shows the emerging database on effective interventions available to improve cognitive performance. The studies also utilise different measures, making meta-analysis impossible. An agreed consensus on measurement may be a useful coordinating mechanism to improve the database. All four interventions show a significant improvement in children’s cognitive and motor development, whether the intervention is directed at the child or at the family/caregiver. The approaches are different with cognitive rehearsal and individual as well as group support. It is unclear if these can be adjusted to lower cost, lower skill and lower intensity for general implementation. They hold out promise for remedial programmes to be scaled up for children with HIV infection. No data exists on complex interventions or combined approaches. The domains with established effective improvement include memory, attention, behavioural parameters, emotional functioning and motor and psychomotor measures. This study does have some limitations. The lack of published evidence does not necessarily reflect the lack of interventions being implemented. Also the inclusion criteria only included articles in English and published literature. There may be relevant data in grey literature and in other languages. The current data clearly describe cognitive delay in HIV-infected and HIV-exposed children. Cognitive delay can be caused by biological factors, environmental factors or both. The trajectory of HIV infection in the family exposes children not only to HIV, ART treatment, but also to ongoing stress and trauma. All of which may affect cognitive performance. The intervention data show potential and suggest that special education interventions are both needed and available. These results should be integrated into programmes and policy as a matter of urgency, to ensure that all children infected and affected by HIV can maximise their potential and benefit from support. References Achenbach, T. M. (1992). Manual for child behaviour checklist/2–3 and 1992 profile. Burlington: Department of Psychiatry, University of Vermont. Achenbach, T. M., & Rescorla, L. A. (2001). Manual for the ASEBA school-age forms & profiles: An integrated system of multi-informant assessment. Burlington: Research Center for Children, Youth, & Families, University of Vermont. Antinori, A., Arendt, G., Becker, J. T., Brew, B. J., Byrd, D. A., Cherner, M., … Wojna, V. E. (2007). Updated research nosology for HIV-associated neurocognitive disorders. Neurology, 69, 1789–1799. doi:10.1212/01.WNL.000028 7431.88658.8b
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Appendix 1 Figure 1. Search strategies.
PsycINFO search
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(adolescent or child or minor or infant or preteen or baby or new born or neonate).mp. [mp = title, abstract, heading word, table of contents, key concepts, original title, tests & measures] (360790) (HIV or human immunodeficiency virus or acquired immunodeficiency syndrome).mp. [mp = title, abstract, heading word, table of contents, key concepts, original title, tests & measures] (33882) Exp HIV/ (29459) 2 or 3 (37198) exp Cognitive Ability/ or exp Neurocognition/ or exp Cognitive Impairment/ or Neurocognitive.mp. or exp Cognitive Development/ (128384) (neurodevelopment* or cognitive development).mp. [mp = title, abstract, heading word, table of contents, key concepts, original title, tests & measures] (33883) (cognitive performance or cognitive functioning). mp. [mp = title, abstract, heading word, table of contents, key concepts, original title, tests & measures] (16639) (memory or language or IQ or spatial awareness or social).mp. [mp = title, abstract, heading word, table of contents, key concepts, original title, tests & measures] (878406) 5 or 6 or 7 or 8 (951766) intervention*.mp. or exp Response to Intervention/ or exp Group Intervention/ or exp Family Intervention/ or exp School-Based Intervention/ or exp Early Intervention/ or exp Intervention/ (219966) exp Rehabilitation/ (55735) 10 or 11 (265129) 1 and 4 and 9 and 12 (442)
MEDLINE search (1)
(adolescent or child or minor or infant or preteen or baby or new born or neonate).mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier] (3010294)
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Whitehead, N., Potterton, J., & Coovadia, A. (2013). The neurodevelopment of HIV-infected infants on HAART compared to HIV-exposed but uninfected infants. AIDS Care, 26, 479–504.
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Child/ (1315568) Infant/ (617618) Adolescent/ (1542458) 1 or 2 or 3 or 4 (3010294) (HIV or human immunodeficiency virus or acquired immunodeficiency syndrome).mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier] (258323) HIV Infections/ (136191) 6 or 7 (258323) Neurocognitive.mp. (8099) (neurodevelopment* or cognitive development).mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier] (16088) (cognitive performance or cognitive functioning). mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier] (14752) (memory or language or IQ or spatial awareness or social).mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier] (744204) 9 or 10 or 11 or 12 (767473) Intervention Studies/ or intervention*.mp. (523134) Rehabilitation/ (16328) 14 or 15 (538777) 5 and 8 and 13 and 16 (1303)
