Abstract
Little is known about how growing up with HIV impacts educational outcomes in sub-Saharan African children. We evaluated if South African children living with HIV (CLWH) were in the appropriate school grade-for-age compared to uninfected control children. We observed higher rates of not being in the correct grade-for-age in CLWH compared with controls (OR 3.32, 95% CI: 2.07–5.34), adjusted for study site, sex, whether the child’s biological father was alive, and caregiver education. Initiation of ART before 6 months of age reduced but did not eliminate this association. Whether these associations are due to biological factors or other social and environmental determinants, and how best to support CLWH to achieve educational goals, warrants further investigation.
Keywords: HIV, disclosure, education, children, pediatrics
Introduction
Currently an estimated 1.8 million children <15 years are living with HIV (CLWH) worldwide, including 1.2 million in Eastern and Southern Africa (UNAIDS, 2017). The success of antiretroviral therapy (ART), particularly when started in the first year of life, has transformed HIV from an acute, fatal disease to a lifelong chronic condition (Hazra, Siberry, & Mofenson, 2010). However, CLWH face a range of complicated issues, including morbidity associated with lifelong HIV infection and ART, and challenges associated with stigma, discrimination, disclosure of a child’s diagnosis, and adherence.
Education is universally recognized to be important for child development, and educational achievement is a predictor of later life health and economic productivity (Link and Phelan, 1995). As CLWH age into adolescence and adulthood, it is important to monitor milestones related to school and employment (Abrams et al., 2018; Mofenson and Cotton, 2013; Sohn and Hazra, 2013). In limited resource settings, there have been studies of educational outcomes in children affected by HIV, defined as having lost one or both parents to HIV/AIDS or living with an HIV-infected parent (Guo, Li, & Sherr, 2012; Orkin, Boyes, Cluver, & Zhang, 2014; Pufall et al., 2014). A review of 23 studies found educational disadvantages among children affected by HIV for various outcomes, including reduced school enrollment, attendance, and performance as well as lower educational attainment (Guo, et al., 2012). However, there are few studies of educational outcomes among CLWH on modern antiretroviral regimens who initiated ART at early ages, particularly in sub-Saharan Africa, which bears 90% of the pediatric HIV epidemic (UNAIDS, 2017). Initiating ART early in the first year or life regardless of clinical symptoms and regardless of CD4 status has been recommended by the World Health Organization since 2008 (Organization, 2006, 2010).
In this study, we investigated whether or not children were in the appropriate grade-for-age in a cohort of school-aged CLWH and controls in South Africa. In addition, we evaluated whether or not there were differences in educational outcomes between CLWH who initiated ART early (<6 months of age) vs. later (≥6 months of age).
Materials and Methods
Study population
Data for this study came from a cross-sectional sample of CLWH and uninfected controls enrolled in Childhood HAART Alterations in Normal Growth, Genes, and aGing Evaluation Study (CHANGES), a longitudinal cohort study of CLWH and HIV-uninfected controls 4–9 years of age at entry into the study in Johannesburg, South Africa (Ramteke et al., 2017). In brief, CHANGES was conducted at two sites: Empilweni Services and Research Unit (ESRU) at Rahima Moosa Mother and Child Hospital and Perinatal HIV Research Unit (PHRU) at Chris Hani Baragwanath Hospital. CLWH previously initiated ART before 3 years of age and had previously participated in clinical trials at these sites (Coovadia et al., 2010; Coovadia et al., 2015; Cotton et al., 2013; Kuhn et al., 2012; Murnane et al., 2017; Violari et al., 2008). HIV-uninfected controls were recruited from children accessing outpatient health services at the two study sites and from siblings and household members of the CLWH. This analysis was conducted using data from the last visit in CHANGES between May 1, 2017 and August 31, 2018. The Institutional Review Boards of Columbia University, New York, NY, USA, and the University of the Witwatersrand, Johannesburg, South Africa approved the study. Children’s guardians provided informed consent and children over 7 years of age provided assent.
Measurements
Socio-demographic information and medical history were obtained through structured interview with the caregiver. Whether the child currently attended school and the child’s current grade were also ascertained during the interview. The primary outcome in this study was whether children were in the appropriate grade-for-age calculated based on the South African Schools Act 84 of 1996. For example, the appropriate grade-for-age of a child aged five and turning six by June 30th in the calendar year of admission to school (January 1 to December 31) would be grade 1. If a child fell behind in school, did not currently attend school or attended a special needs school, they were considered to not be in the appropriate grade-for-age. Secondary outcomes included whether the child had ever failed a year at school and school non-attendance (number of days of school missed in the past month because of a health problem). Also included in the interview were questions on whether the child has been hospitalized since the last visit (yes/no) and whether the child misses school to go to the doctor or hospital (never, almost never, sometimes, often, almost always).
At the same study visit at which caregiver interview was obtained, plasma HIV-RNA levels (lower limit of detection 40 copies/ml) were measured by the Abbott RealTime HIV-1 Assay (Abbott Park, Illinois, USA). CD4 counts and percentages were measured by the TruCount Method (BD Biosciences, Germany) for CLWH.
Statistical Analysis
Characteristics and educational outcomes were compared between groups using parametric t-tests for continuous variables that met standard assumptions and the chi-squared or Fisher’s exact tests for categorical variables. To evaluate factors associated with not being in the appropriate grade-for-age in all children, unadjusted odds ratios (ORs) and confidence intervals (95% CIs) were estimated using logistic regression. Characteristics marginally associated with not being in the appropriate grade-for-age (p-value <0.10) were included in a multivariable model to estimate adjusted ORs (aORs). The analysis was repeated among CLWH only including additional HIV-specific factors, including age at ART initiation (<6 months of age vs. ≥6 months of age). All p-values are 2-tailed and p-values <0.05 were considered statistically significant. Statistical calculations were performed using SAS version 9.4 (Cary, North Carolina, USA).
Results
Study participants
A total of 480 CLWH and 130 controls were included in this analysis. Approximately 20% of the controls were siblings or household members of CLWH and 80% were accessing outpatient health services at sites. Their characteristics are shown in Table 1. Children were an average of 10.8 years of age (range 7.0–14.0 years) and mean age was similar in both groups (10.8 vs. 10.8 years, p=0.51). There were fewer boys in the CLWH group compared to the control group (45.6 vs. 58.5%, p=0.009). The primary caregiver was the biological mother for 84.8% of CLWH and 96.2% of controls (<0.001). A smaller proportion of biological mothers (93.1 vs. 98.5%, p=0.07) and fathers (83.3 vs. 90.8%, p=0.09) were alive for CLWH compared to controls. A similar proportion of CLWH and controls had a foreign-born parent (18.5 vs. 17.7%, p=0.82). About half of caregivers for CLWH and controls completed high school (52.9 vs. 45.4%, p=0.13). Most CLWH and controls lived in a house (67.3 vs. 63.1%, p=0.37). Others lived in a flat, shack, rented room, outbuilding, or hostel. Similar proportions of CLWH and controls had been admitted to the hospital since the last visit (1.3% vs. 3.1%, p=0.23). 13.9% of caregivers of CLWH reported that children had to miss school to go to the doctor or hospital “often” or “almost always” compared to 0% of controls.
Table 1.
Clinical and demographic characteristics of children living with HIV (CLWH) vs. controls
| CLWH (n=480) | Controls (n=130) | P | |
|---|---|---|---|
| Age (years), Mean (SD) | 10.8 (1.3) | 10.8 (1.7) | 0.51 |
| Age (years), Range | 7.8 – 14.0 | 7.5 – 14.1 | - |
| Sex, N (%) | 0.009 | ||
| Male | 219 (45.6) | 76 (58.5) | |
| Female | 261 (54.4) | 54 (41.5) | |
| Biological mother’s HIV status, N (%) | - | ||
| HIV-positive | 480 (100.0) | 43 (33.1) | |
| HIV-negative | 0 (0.0) | 84 (64.6) | |
| Unknown | 0 (0.0) | 3 (2.3) | |
| Mother is primary caregiver, N (%) | <0.001 | ||
| Yes | 407 (84.8) | 125 (96.2) | |
| No | 73 (15.2) | 5 (3.8) | |
| Biological mother is alive, N (%) | 0.07 | ||
| Yes | 447 (93.1) | 128 (98.5) | |
| No | 31 (6.5) | 2 (1.5) | |
| Unknown | 2 (0.4) | 0 (0.0) | |
| Biological father is alive, N (%) | 0.09 | ||
| Yes | 400 (83.3) | 118 (90.8) | |
| No | 67 (14.0) | 9 (6.9) | |
| Unknown | 13 (2.7) | 3 (2.3) | |
| Child has a foreign-born parent, N (%) | 0.82 | ||
| Yes | 89 (18.5) | 23 (17.7) | |
| No | 391 (81.5) | 107 (82.3) | |
| Caregiver educational attainment, N (%) | 0.13 | ||
| No school / did not finish high school | 254 (52.9) | 59 (45.4) | |
| Completed high school | 226 (47.1) | 71 (54.6) | |
| Child lives in a house, N (%) | 0.37 | ||
| Yes | 323 (67.3) | 82 (63.1) | |
| No | 157 (32.7) | 48 (36.9) | |
| Caregiver lost job in past 6 months, N (%) | 0.003 | ||
| Yes | 51 (10.6) | 3 (2.3) | |
| No | 429 (89.4) | 127 (97.7) | |
| Child admitted to hospital since last visit, N (%) | 0.23 | ||
| Yes | 6 (1.3) | 4 (3.1) | |
| No | 474 (98.8) | 126 (96.9) | |
| Child misses school to go to the doctor or hospital, N (%) | <0.001 | ||
| Never | 90 (19.2) | 44 (34.1) | |
| Almost never | 7 (1.5) | 6 (4.7) | |
| Sometimes | 306 (65.4) | 79 (61.2) | |
| Often | 58 (12.4) | 0 (0.0) | |
| Almost always | 7 (1.5) | 0 (0.0) |
All CLWH previously initiated ART before 3 years of age, including 82% before 1 year of age. The median age at ART initiation was 4.4 months of age (IQR: 2.0–9.1 months); 303 (63.1%) initiated ART <6 months of age and 177 (36.7%) initiated ART ≥6 months of age. Current mean CD4 percentage was 36.1 ± 6.7% and 429 (89.9%) had a suppressed HIV RNA <40 copies/mL. Most children (60.4%) were currently on a lopinavir/ritonavir-based ART regimen, with 37.1% on an efavirenz-based regimen and 2.5% on another regimen.
HIV and education
Overall, 45.8% of CLWH were not in the appropriate grade-for-age compared to 30.0% of controls (p<0.01). As shown in Table 2, CLWH were twice as likely to not be in the appropriate grade-for-age compared to controls (OR: 1.97, 95% CI: 1.30–2.99) in unadjusted analyses. Compared to girls, boys were twice as likely not to be in the appropriate grade-for-age (OR: 1.90, 95%CI: 1.37–2.63). Not having a living biological father vs. having one (OR: 1.62, 95% CI: 0.99–2.62) and less caregiver education (not completing high school vs. completing high school) were also associated with not being in the correct grade-for-age (OR: 1.46, 95% CI: 1.06–2.02). Whether or not the child had a living biological mother, had their biological mother as their primary caregiver, had a foreign-born parent, or lived in a house were not associated with not being in the appropriate grade-for-age. Among controls, there was no difference in being the appropriate grade-for-age between those with an HIV-positive mother and those with an HIV-negative mother (data not shown).
Table 2.
Factors associated with not being in the appropriate grade-for-age, all children
| Factor | n/N (%) | Unadjusted OR (95% CI) | P | Adjusted OR* (95% CI) | P |
|---|---|---|---|---|---|
| HIV status | |||||
| CLWH | 220/480 (45.8) | 1.97 (1.30, 2.99) | 0.001 | 3.32 (2.07, 5.34) | <0.0001 |
| Controls | 39/130 (30.0) | 1.00 | 1.0 | ||
| Site | |||||
| ESRU | 175/365 (48.0) | 1.77 (1.26, 2.47) | 0.0009 | 2.61 (1.78, 3.84) | <0.0001 |
| PHRU | 84/245 (34.3) | 1.00 | 1.0 | ||
| Age in years | 0.99 (0.89, 1.11) | 0.91 | |||
| Sex | |||||
| Male | 149/295 (50.5) | 1.90 (1.37, 2.63) | 0.0001 | 2.01 (1.42, 2.85) | <0.0001 |
| Female | 110/315 (34.9) | 1.00 | |||
| Biological mother is primary caregiver | |||||
| No | 33/78 (42.3) | 0.99 (0.61, 1.61) | 0.98 | ||
| Yes | 226/532 (42.5) | 1.00 | |||
| Biological mother is alive | |||||
| No | 16/33 (48.5) | 1.30 (0.65, 2.63) | 0.46 | ||
| Yes | 241/575 (41.9) | 1.00 | |||
| Biological father is alive | |||||
| No | 40/76 (52.6) | 1.62 (0.99, 2.62) | 0.051 | 1.50 (0.90, 2.50) | 0.12 |
| Yes | 211/518 (40.7) | 1.00 | |||
| Highest caregiver grade completed | |||||
| No school / did not finish high school | 147/313 (47.0) | 1.46 (1.06, 2.02) | 0.021 | 1.56 (1.11, 2.21) | 0.012 |
| Completed high school | 112/297 (37.7) | 1.00 | |||
| Child lives in a house | |||||
| No | 94/205 (45.9) | 1.23 (0.88, 1.73) | 0.23 | - | - |
| Yes | 165/405 (40.7) | 1.00 | |||
| Has a foreign-born parent | |||||
| Yes | 48/112 (42.9) | 1.02 (0.67, 1.54) | 0.92 | ||
| No | 211/498 (42.4) | 1.0 |
The adjusted model includes all variables with p<0.10 in unadjusted analysis.
As shown in Table 2, after adjusting for site, sex, whether the child’s biological father was alive, and caregiver education, CLWH were more likely not to be in the appropriate grade-for-age compared to uninfected children (aOR: 3.32, 95% CI: 2.07–5.34). Educational delay was more common in boys (aOR: 2.01, 95% CI: 1.42–2.85) and more common among children whose caregivers who did not complete high school compared to those who did (aOR: 1.56, 95% CI: 1.11–2.21). There was no interaction between HIV status and sex (interaction term p=0.79).
Similar proportions of CLWH and controls had ever failed a year at school (29.8 vs. 23.1%, p=0.32). Among CLWH, 12.8%, 7.1%, and 4.8% missed 1, 2, and 3 days of school in the past month because of a health problem, respectively, compared to 7.8%, 2.6%, and 2.6% of controls (p=0.003).
Age at ART initiation and education
Stratifying by age at ART initiation, 55.9% who initiated ART >6 months ever had educational delay compared to 39.9% who initiated ≤6 months (p=0.0007). Among all children, those who initiated ART >6 months (aOR: 4.01; 95% CI: 2.39–6.72) and who initiated ≤6 months (aOR: 2.72, 95% CI: 1.62–4.57) were more likely to have educational delays than uninfected controls, adjusted for site, sex, whether the child’s biological father was alive, and caregiver education.
As shown in Table 3, among CLWH only, initiating ART >6 months was associated with not being in the appropriate grade-for-age, adjusted for sex, site, whether the child’s biological father was alive, current ART regimen, and whether the child has been told his/her HIV status (aOR: 1.74, 95% CI: 1.05–2.88). In the adjusted analysis, male CLWH were more likely not to be in the correct grade compared to females (aOR: 1.67, 95% CI: 1.08–2.57). Those who had not been told his/her HIV status were also more likely not to be in the correct grade-for-age (aOR: 1.87, 95% CI: 1.18–2.95).
Table 3.
Factors associated with not being in the appropriate grade-for-age, children living with HIV (CLWH)
| Factor | n/N (%) | Unadjusted OR (95% CI) | P | Adjusted OR (95% CI)* | P |
|---|---|---|---|---|---|
| Age at ART initiation | |||||
| ≥6 months | 99/177 (55.9) | 1.91 (1.31, 2.78) | 0.0007 | 1.74 (1.05, 2.88) | 0.032 |
| <6 months | 121/303 (39.9) | 1.0 | 1.0 | ||
| Age in years | 1.00 (0.87, 1.14) | 0.98 | |||
| Sex | |||||
| Male | 121/219 (55.3) | 2.02 (1.40, 2.91) | 0.0002 | 1.67 (1.08, 2.57) | 0.021 |
| Female | 99/261 (37.9) | 1.0 | 1.0 | ||
| Site | |||||
| ESRU | 136/235 (57.9) | 2.63 (1.82, 3.81) | <0.0001 | 1.96 (0.99, 3.87) | 0.054 |
| PHRU | 84/245 (34.3) | 1.0 | 1.0 | ||
| Biological mother is primary caregiver | |||||
| No | 32/73 (43.8) | 0.91 (0.55, 1.50) | 0.71 | - | - |
| Yes | 188/407 (46.2) | 1.0 | |||
| Biological mother is alive | |||||
| No | 202/447 (45.2) | 1.29 (0.62, 2.68) | 0.49 | - | - |
| Yes | 16/31 (51.6) | 1.0 | |||
| Biological father is alive | |||||
| No | 176/400 (44.0) | 1.57 (0.93, 2.64) | 0.09 | 1.57 (0.85, 2.90) | 0.15 |
| Yes | 37/67 (55.2) | 1.0 | |||
| Highest caregiver grade completed | |||||
| No school / did not finish high school | 125/254 (49.2) | 1.34 (0.93, 1.92) | 0.12 | - | - |
| Completed high school | 95/226 (42.0) | 1.0 | |||
| Child lives in a house | |||||
| No | 142/323 (44.0) | 1.26 (0.86, 1.85) | 0.24 | - | - |
| Yes | 78/157 (49.7) | 1.0 | |||
| Has a foreign born parent | |||||
| Yes | 177/391 (45.3) | 1.13 (0.71, 1.79) | 0.60 | - | - |
| No | 43/89 (48.3) | 1.0 | |||
| Current plasma HIV RNA (copies/ml) | |||||
| Not suppressed >40 | 26/48 (54.2) | 1.45 (0.79, 2.63) | 0.23 | - | - |
| Suppressed <40 | 193/429 (45.0) | 1.0 | |||
| Current CD4 percentage (%) | 1.00 (0.97, 1.03) | 0.99 | - | - | |
| Current ART regimen | |||||
| EFV-based | 103/178 (57.9) | 2.15 (1.47, 3.15) | <0.0001 | 0.86 (0.44, 1.68) | 0.67 |
| LPV/r-based | 113/290 (39.0) | 1.0 | 1.0 | 0.75 | |
| Other | 4/12 (33.3) | 0.78 (0.23, 2.66) | 0.70 | 0.78 (0.17, 3.51) | |
| Child has been told his/her HIV status | |||||
| No | 120/222 (54.1) | 1.82 (1.27, 2.63) | 0.001 | 1.87 (1.18, 2.95) | 0.008 |
| Yes | 100/255 (39.2) | 1.0 | 1.0 | ||
| Don’t know | 0/3 (0.0) | - | - | ||
| Pre-treatment HIV RNA (copies/ml) | |||||
| <100,000 | 20/35 (57.1) | 1.0 | 1.0 | ||
| 100,000–340,000 | 23/65 (35.4) | 0.41 (0.18, 0.95) | 0.04 | 0.40 (0.16, 0.99) | 0.047 |
| 340,000–750,000 | 33/68 (48.5) | 0.71 (0.31, 1.61) | 0.41 | 0.92 (0.37, 2.27) | 0.85 |
| ≥750,000 | 113/245 (46.1) | 0.64 (0.31, 1.31) | 0.22 | 0.73 (0.33, 1.59) | 0.42 |
| Pre-treatment CD4 percentage (%) | 0.96 (0.95, 0.98) | <0.0001 | 0.97 (0.96, 1.00) | 0.054 |
The adjusted model includes all variables with p<0.10 in unadjusted analysis.
Discussion
In a cohort of children in South Africa, we observed higher rates of not being in the correct grade-for-age in CLWH compared with uninfected children. All CLWH had started treatment within the first 3 years of life, most prior to 1 year of age, and were maintained in care, mostly well-suppressed on ART. Although all CLWH had poorer educational outcomes than controls regardless of the timing of ART initiation, those who initiated ART early had better outcomes than those initiating ART later.
Few studies have assessed educational outcomes in CLWH. A study of children aged 6–17 in Zimbabwe did not find any association between HIV status and being in the correct grade-for-age, defined as being more than two years behind in school (Pufall, et al., 2014). Of interest, a mixed-methods study of primary school children in Zimbabwe found that children who were one or more class grades behind in school due to illness were more likely to be HIV-infected compared to children who were not (Bandason et al., 2013). A recent study in Rwanda found that HIV-positive children were twice as likely to be overage for their grade compared to HIV-unaffected children (Henning et al., 2018). These studies did not specify whether children with HIV were on ART or virologically suppressed. In our cohort, caregivers of CLWH reported that their children had to miss school for medical visits more often than caregivers of controls.
Comparable to other studies in this age group, boys in our cohort had more educational delay than girls. A community-based study of children aged 4–13 years conducted in HIV-affected communities in South Africa and Malawi found boys with HIV to be less often in the correct grade-for-age (Hensels et al., 2016). Among CLWH, children who had not been told their HIV status were more likely not to be in the correct grade-for-age. The decision of how and when to disclose HIV status to children is complex and necessitates a developmentally appropriate process; this finding may reflect delays in child development. In addition, there may be unmeasured family or household dynamics or psychosocial circumstances that affect both disclosure of HIV status as well as educational outcomes (Finnegan et al., 2019; Hayfron-Benjamin, Obiri-Yeboah, Ayisi-Addo, Siakwa, & Mupepi, 2018; Kalembo, Kendall, Ali, & Chimwaza, 2019; Kiwanuka, Mulogo, & Haberer, 2014).
It is unclear whether these associations are due to actual biological factors or other social and environmental factors. A review of children affected by HIV and educational outcomes emphasized incorporating measures of individual and contextual factors, such as caregiver gender and poverty, in studies of educational outcomes (Guo, et al., 2012). We adjusted for sociodemographic variables to the best of our ability in our study. In addition, many of the children in our control group came from the same family or households as CLWH. One potential mechanism for poorer educational outcomes among CLWH is neurodevelopmental impairment, a major co-morbidity associated with HIV (Chiriboga, Fleishman, Champion, Gaye-Robinson, & Abrams, 2005; Koekkoek et al., 2006; Patel et al., 2009; van Arnhem et al., 2013). Studies have found higher rates of cognitive impairment in CLWH compared with controls (Abubakar, Van Baar, Van de Vijver, Holding, & Newton, 2008; Boivin et al., 1995; McGrath et al., 2006; Msellati et al., 1993). It is possible that earlier ART may mitigate these effects. There is a growing body of evidence that indicates early ART may have benefits for a number of clinical outcomes including growth, virologic control, and neurodevelopment (Laughton et al., 2012; Shiau et al., 2013; Shiau et al., 2017). This is the first study to report on the timing of ART initiation and educational outcomes in CLWH who were initiated on ART in the first few years of life and well-maintained on treatment. However, even early and prolonged treatment did not completely mitigate these outcomes. Further studies evaluating long-term outcomes of starting ART even earlier (in the neonatal period) are warranted.
Our study is limited by a single educational outcome, albeit an important one. Future studies should include other more extensive educational outcomes, including academic achievement, other aspects of school performance, and completion of primary and secondary school. In addition, other family or contextual factors (e.g. distance to school, school quality) that might support or impede school attendance and academic achievement should be included, as well as other measures of socioeconomic status associated with access to education. These factors may potentially be related to the differences observed by study site. Of note, we did observe that CLWH missed school for scheduled appointments for monitoring HIV more often than controls. Our study was also limited in that our control group included siblings of CLWH and other children affected by HIV.
In conclusion, educational delay appears to be greater in CLWH, particularly those who have delayed treatment initiation. Progressing through school in a timely manner is important for school performance, school completion, and the onset of other life transitions for adolescents. School disengagement can place children at risk for other behaviors, such as substance use, early sexual debut, or gang involvement, resulting in poorer psychological, physical, social, and economic health. Regardless of underlying cause, interventions to improve timely progression through school are needed. In addition, accommodations to healthcare visits (i.e. after school or weekend medical appointments) may minimize school absences.
Acknowledgments:
This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development under Grant numbers HD 073977 and HD 073952.
Footnotes
Disclosure of Interest Statement:
The authors have no conflicts of interest to report.
References
- Abrams EJ, Mellins CA, Bucek A, Dolezal C, Raymond J, Wiznia A, … Ng YKW (2018). Behavioral Health and Adult Milestones in Young Adults With Perinatal HIV Infection or Exposure. Pediatrics, 142(3)doi: 10.1542/peds.2018-0938 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Abubakar A, Van Baar A, Van de Vijver FJ, Holding P, & Newton CR (2008). Paediatric HIV and neurodevelopment in sub-Saharan Africa: a systematic review. Trop Med Int Health, 13(7), pp. 880–887. doi: 10.1111/j.1365-3156.2008.02079.x [DOI] [PubMed] [Google Scholar]
- Bandason T, Langhaug LF, Makamba M, Laver S, Hatzold K, Mahere S, … Ferrand RA (2013). Burden of HIV among primary school children and feasibility of primary school-linked HIV testing in Harare, Zimbabwe: a mixed methods study. AIDS Care, 25(12), pp. 1520–1526. doi: 10.1080/09540121.2013.780120 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boivin MJ, Green SD, Davies AG, Giordani B, Mokili JK, & Cutting WA (1995). A preliminary evaluation of the cognitive and motor effects of pediatric HIV infection in Zairian children. Health Psychol, 14(1), pp. 13–21. [DOI] [PubMed] [Google Scholar]
- Chiriboga CA, Fleishman S, Champion S, Gaye-Robinson L, & Abrams EJ (2005). Incidence and prevalence of HIV encephalopathy in children with HIV infection receiving highly active anti-retroviral therapy (HAART). J Pediatr, 146(3), pp. 402–407. doi: 10.1016/j.jpeds.2004.10.021 [DOI] [PubMed] [Google Scholar]
- Coovadia A, Abrams EJ, Stehlau R, Meyers T, Martens L, Sherman G, … Kuhn L (2010). Reuse of nevirapine in exposed HIV-infected children after protease inhibitor-based viral suppression: a randomized controlled trial. JAMA, 304(10), pp. 1082–1090. doi: 10.1001/jama.2010.1278 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coovadia A, Abrams EJ, Strehlau R, Shiau S, Pinillos F, Martens L, … Kuhn L (2015). Efavirenz-Based Antiretroviral Therapy Among Nevirapine-Exposed HIV-Infected Children in South Africa: A Randomized Clinical Trial. JAMA, 314(17), pp. 1808–1817. doi: 10.1001/jama.2015.13631 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cotton MF, Violari A, Otwombe K, Panchia R, Dobbels E, Rabie H, … Babiker AG (2013). Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial. Lancet, 382(9904), pp. 1555–1563. doi: 10.1016/s0140-6736(13)61409-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finnegan A, Langhaug L, Schenk K, Puffer ES, Rusakaniko S, Choi Y, … Green EP (2019). The prevalence and process of pediatric HIV disclosure: A population-based prospective cohort study in Zimbabwe. PLoS One, 14(5), p e0215659. doi: 10.1371/journal.pone.0215659 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guo Y, Li X, & Sherr L (2012). The impact of HIV/AIDS on children’s educational outcome: a critical review of global literature. AIDS Care, 24(8), pp. 993–1012. doi: 10.1080/09540121.2012.668170 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hayfron-Benjamin A, Obiri-Yeboah D, Ayisi-Addo S, Siakwa PM, & Mupepi S (2018). HIV diagnosis disclosure to infected children and adolescents; challenges of family caregivers in the Central Region of Ghana. BMC Pediatr, 18(1), p 365. doi: 10.1186/s12887-018-1330-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hazra R, Siberry GK, & Mofenson LM (2010). Growing up with HIV: children, adolescents, and young adults with perinatally acquired HIV infection. Annu Rev Med, 61, pp. 169–185. doi: 10.1146/annurev.med.050108.151127 [DOI] [PubMed] [Google Scholar]
- Henning M, Kirk CM, Franchett E, Wilder R, Sezibera V, Ukundineza C, & Betancourt T (2018). Over-age and underserved: a case control study of HIV-affected children and education in Rwanda. Vulnerable Children and Youth Studies, 13(1), pp. 81–93. [Google Scholar]
- Hensels IS, Sherr L, Skeen S, Macedo A, Roberts KJ, & Tomlinson M (2016). Do not forget the boys - gender differences in children living in high HIV-affected communities in South Africa and Malawi in a longitudinal, community-based study. AIDS Care, 28 Suppl 2, pp. 100–109. doi: 10.1080/09540121.2016.1176680 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kalembo FW, Kendall GE, Ali M, & Chimwaza AF (2019). Socio-demographic, clinical, and psychosocial factors associated with primary caregivers’ decisions regarding HIV disclosure to their child aged between 6 and 12 years living with HIV in Malawi. PLoS One, 14(1), p e0210781. doi: 10.1371/journal.pone.0210781 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kiwanuka J, Mulogo E, & Haberer JE (2014). Caregiver perceptions and motivation for disclosing or concealing the diagnosis of HIV infection to children receiving HIV care in Mbarara, Uganda: a qualitative study. PLoS One, 9(3), p e93276. doi: 10.1371/journal.pone.0093276 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koekkoek S, Eggermont L, De Sonneville L, Jupimai T, Wicharuk S, Apateerapong W, … Ananworanich J (2006). Effects of highly active antiretroviral therapy (HAART) on psychomotor performance in children with HIV disease. J Neurol, 253(12), pp. 1615–1624. doi: 10.1007/s00415-006-0277-x [DOI] [PubMed] [Google Scholar]
- Kuhn L, Coovadia A, Strehlau R, Martens L, Hu CC, Meyers T, … Abrams EJ (2012). Switching children previously exposed to nevirapine to nevirapine-based treatment after initial suppression with a protease-inhibitor-based regimen: long-term follow-up of a randomised, open-label trial. Lancet Infect Dis, 12(7), pp. 521–530. doi: 10.1016/s1473-3099(12)70051-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laughton B, Cornell M, Grove D, Kidd M, Springer PE, Dobbels E, … Cotton MF (2012). Early antiretroviral therapy improves neurodevelopmental outcomes in infants. Aids, 26(13), pp. 1685–1690. doi: 10.1097/QAD.0b013e328355d0ce [DOI] [PMC free article] [PubMed] [Google Scholar]
- Link BG, & Phelan J (1995). Social conditions as fundamental causes of disease. J Health Soc Behav, Spec No, pp. 80–94. [PubMed] [Google Scholar]
- McGrath N, Fawzi WW, Bellinger D, Robins J, Msamanga GI, Manji K, & Tronick E (2006). The timing of mother-to-child transmission of human immunodeficiency virus infection and the neurodevelopment of children in Tanzania. Pediatr Infect Dis J, 25(1), pp. 47–52. [DOI] [PubMed] [Google Scholar]
- Mofenson LM, & Cotton MF (2013). The challenges of success: adolescents with perinatal HIV infection. J Int AIDS Soc, 16, p 18650. doi: 10.7448/ias.16.1.18650 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Msellati P, Lepage P, Hitimana DG, Van Goethem C, Van de Perre P, & Dabis F (1993). Neurodevelopmental testing of children born to human immunodeficiency virus type 1 seropositive and seronegative mothers: a prospective cohort study in Kigali, Rwanda. Pediatrics, 92(6), pp. 843–848. [PubMed] [Google Scholar]
- Murnane PM, Strehlau R, Shiau S, Patel F, Mbete N, Hunt G, … Kuhn L (2017). Switching to efavirenz versus remaining on ritonavir-boosted lopinavir in HIV-infected children exposed to nevirapine: long-term outcomes of a randomized trial. Clin Infect Dis doi: 10.1093/cid/cix335 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Organization, W. H. (2006). Antiretroviral therapy of HIV infection in infants and children: towards universal access - recommendations for a public health approach. Retrieved Date from http://www.who.int/hiv/pub/guidelines/paediatric020907.pdf. [PubMed]
- Organization, W. H. (2010). Antiretroviral therapy for HIV infection in infants and children: towards universal access - recommendations for a public health approach: 2010 revision. Retrieved Date from http://www.who.int/hiv/pub/paediatric/infants2010/en/index.html. [PubMed]
- Orkin M, Boyes ME, Cluver LD, & Zhang Y (2014). Pathways to poor educational outcomes for HIV/AIDS-affected youth in South Africa. AIDS Care, 26(3), pp. 343–350. doi: 10.1080/09540121.2013.824533 [DOI] [PubMed] [Google Scholar]
- Patel K, Ming X, Williams PL, Robertson KR, Oleske JM, & Seage GR 3rd. (2009). Impact of HAART and CNS-penetrating antiretroviral regimens on HIV encephalopathy among perinatally infected children and adolescents. AIDS, 23(14), pp. 1893–1901. doi: 10.1097/QAD.0b013e32832dc041 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pufall EL, Nyamukapa C, Eaton JW, Campbell C, Skovdal M, Munyati S, … Gregson S (2014). The impact of HIV on children’s education in eastern Zimbabwe. AIDS Care, 26(9), pp. 1136–1143. doi: 10.1080/09540121.2014.892564 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramteke SM, Shiau S, Foca M, Strehlau R, Pinillos F, Patel F, … Arpadi SM (2017). Patterns of Growth, Body Composition, and Lipid Profiles in a South African Cohort of Human Immunodeficiency Virus-Infected and Uninfected Children: A Cross-Sectional Study. J Pediatric Infect Dis Soc doi: 10.1093/jpids/pix026 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shiau S, Arpadi S, Strehlau R, Martens L, Patel F, Coovadia A, … Kuhn L (2013). Initiation of antiretroviral therapy before 6 months of age is associated with faster growth recovery in South African children perinatally infected with human immunodeficiency virus. J Pediatr, 162(6), pp. 1138–1145, 1145.e1131–1132. doi:10.1016/j.jpeds.2012.11.025 Retrieved from 10.1016/j.jpeds.2012.11.025https://www.ncbi.nlm.nih.gov/pubmed/23312691 Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23312691 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shiau S, Strehlau R, Technau KG, Patel F, Arpadi SM, Coovadia A, … Kuhn L (2017). Early age at start of antiretroviral therapy associated with better virologic control after initial suppression in HIV-infected infants. AIDS, 31(3), pp. 355–364. doi: 10.1097/qad.0000000000001312 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sohn AH, & Hazra R (2013). The changing epidemiology of the global paediatric HIV epidemic: keeping track of perinatally HIV-infected adolescents. J Int AIDS Soc, 16, p 18555. doi: 10.7448/ias.16.1.18555 [DOI] [PMC free article] [PubMed] [Google Scholar]
- UNAIDS. (2017). AIDSinfo Online Database. Retrieved Date from http://aidsinfo.unaids.org/].
- van Arnhem LA, Bunders MJ, Scherpbier HJ, Majoie CB, Reneman L, Frinking O, … Pajkrt D (2013). Neurologic abnormalities in HIV-1 infected children in the era of combination antiretroviral therapy. PLoS One, 8(5), p e64398. doi: 10.1371/journal.pone.0064398 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, … McIntyre JA (2008). Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med, 359(21), pp. 2233–2244. doi: 10.1056/NEJMoa0800971 [DOI] [PMC free article] [PubMed] [Google Scholar]