Background
In 2015, WHO recommended initiating antiretroviral therapy (ART) for all children with HIV immediately after the diagnosis regardless of their clinical stages and CD4 cell counts [
1]. Although enormous efforts have been taken to promote early ART worldwide, ART coverage among HIV-infected children remained low. Among an estimated 1.7 million HIV-infected children aged 15 years and younger in 2021, only 52.0% of them received ART [
2]. In China, ART coverage among HIV-infected children was relatively higher as a result of the effective expansion of HIV treatment in recent years, for example, by the end of 2020, 95.2% of 7,935 HIV-infected children younger than 15 years old were on ART [
3]. In general, pediatric HIV treatment faced unique challenges. The viral suppression rate decreased markedly after ART initiation from 64% in the first year and 62% in the second year to 59% in the third year [
4]. Being unable to maintain viral suppression often indicates virological failure. Adherence, a major factor associated with viral suppression [
5], was reported particularly low with a range of 53% to 84% among HIV-infected adolescents [
6]. Further, the risk of loss to follow-up was higher among adolescents aged 11 to 19 years compared to adults and young children [
7].
There are three groups regarding children affected by HIV in the literature, including HIV-exposed but uninfected children (HEU), HIV-infected children who acquired HIV through the mother-to-child transmission route, and HIV-infected children who acquired HIV through the sexual transmission route. Children from the three groups may differ in their neuropsychiatric presentations, specifically attentional, cognitive, and emotional dysregulation [
8‐
10]. Compared to HIV-unexposed, uninfected children (HUU), both HEU children and HIV-infected children face mental health challenges [
11,
12]. Behavioral and emotional difficulties (BEDs) refer to a variety of behavioral and emotional abnormalities that occur in children before the age of 18 and predominantly manifest as anxiety, fear, depression, hyperactivity, impulsivity, and disobedience [
13]. HEU children had an increased risk of having psychiatric disorders compared to HUU children [
12]. Further, previous studies reported that HIV-infected children were more likely to suffer from BEDs than their HIV-negative peers [
14,
15]. The reasons included the physical and neurological effects of HIV infection on behavior, emotion, and cognition as well as social and emotional effects due to various stressors HIV-infected children often face, which were associated with HIV infection and treatment [
15,
16]. Some social challenges faced by HIV-infected children included poverty, HIV stigma, relationship difficulty related to HIV disclosure, and the school system’s inability to meet their needs [
17]. In addition, previous studies reported that parental involvement, parents’ perception and attitude toward medication taking were associated with children’s medication adherence [
18,
19].
However, the literature has not clearly demonstrated the effects of BEDs on treatment outcomes in HIV-infected children who were receiving ART or reported inconsistent results [
14,
20‐
23]. Two previous studies reported that BEDs were associated with nonadherence among HIV-infected adolescents [
20,
21]. Another study found that HIV-infected adolescents who screened positive for depression, post-traumatic stress disorder, and substance use had a higher likelihood of an unsuppressed viral load [
22]. Other previous studies reported inconsistent results, for example, BEDs were only associated with adherence in HIV-infected male children [
23], and no association between BEDs and virological failure [
14]. In addition, previous studies related to BEDs of HIV-infected children have been mainly conducted in Africa and Western countries [
11,
24]. A gap existed in the HIV-infected children BEDs literature in Asian studies. This study aimed to describe the prevalence of BEDs among HIV-infected children on ART in rural southwestern China and identify the factors associated with HIV treatment outcomes, specifically, medication adherence and virological failure.
Discussion
The prevalence of 16.9% for an abnormal score of the total difficulties scale was consistent with previous studies conducted among HIV-infected children on ART, which had a range between 6.4% to 43.6% [
14,
20,
33,
34]. The study that generated Shanghai norms used a representative sample of children aged 11–17 years from 12 of the 19 districts in Shanghai [
28]. HIV-infected children on ART have shown higher prevalence of BEDs compared to Shanghai norms [
28]. Further, compared to Shanghai norms, HIV-infected children on ART in our study were more likely to develop emotional symptoms, had higher rates of conduct problems, and were less likely to have prosocial behavior [
28]. This study did not find a significant difference between HIV-infected children and Shanghai norms on peer problems and hyperactivity [
28]. Future studies could explore in depth the reasons that result in the differences in BEDs between HIV-infected children and children in the general population.
This study found a gender difference in three BEDs subscales. Females showed a higher score on emotional symptoms, while males demonstrated more peer problems and poor prosocial behavior. These results were all consistent with the findings in the general population aged 12–18 years in the previous studies [
35]. In previous studies investigating HIV-infected children, one study reported males were more likely to suffer from emotional symptoms [
23], and no gender differences in peer problems were found in a study conducted in Africa [
15]. The gender difference in BEDs for HIV-infected children has implications in pediatric HIV care, in which care providers must pay attention to the unique needs of male and female children and offer specific trainings and coping skills to children with BEDs.
This study found that HIV-infected children with abnormal SDQ-C total difficulties score were more likely missing doses for ART medications in the past month. This result was consistent with previous findings demonstrating that BEDs were negatively associated with medication adherence [
20,
21,
36]. Pediatric HIV care providers must work with adolescents and their parents or guardians to develop a plan to maintain a good medication adherence and identify any possible obstacles for adherence at ART initiation. For children who could not adhere to their medication due to BEDs, psychological professionals must be referred to these patients. Further, this study also found that parents’ support was critical for HIV-infected children to adhere to their medications. This result was consistent with previous findings [
37]. Parents played a vital role in supporting HIV-infected children financially, physically, and emotionally, also most children relied on their parents to access HIV care and to manage their medications [
38]. Therefore, pediatric HIV care providers must work together with parents in addressing HIV-related issues that children encounter, for example, provide trainings to patients on medication management.
Some factors were found to be associated with virological failure, including age of 14–17, being female, and having missed doses in the past month. Some previous studies also found that older children had a higher risk of virological failure [
39,
40], which could be explained by the poorer adherence and higher likelihood of drug resistance in older children [
39,
41]. Future studies are still needed to further testify this association and verify the reasons between age and virological failure because other previous studies did not detect this association [
42,
43]. In this study, females were 2.21 times more likely to experience virological failure compared to males. This result was consistent with previous studies, which showed that females were roughly 2.50 times more likely to experience virological failure than males [
44,
45]. However, other previous studies reported either a higher risk of virological failure in males [
43], or no association between gender and virological failure [
39,
42]. The inconclusive result on this association needs to be further assessed in large and diverse samples in future studies. Further, the association between nonadherence and virological failure has been well proven in previous studies [
39,
41,
42].
Although this study did not identify a direct association between BEDs and virological failure, children’s behavioral and emotional status were undoubtedly a critical factor on HIV outcomes because the indirect association through adherence was identified. Further, children’s behavioral and emotional status was a vital factor involving with their daily life and well-being. HIV-infected children were vulnerable population for BEDs, pediatric HIV care providers and parents must pay more attention to children’s social, behavioral, and emotional needs and provide support in their daily lives, not only on HIV care and medication management, but also on coping with social, emotional, and relationship issues.
This study has limitations. The cross-sectional study design was unable to generate causal relationships between BEDs and HIV treatment outcomes. Future studies could consider examining the associations using experimental or longitudinal study designs. This study sample was HIV-infected children aged 11 to 19 years resided in Guangxi. The study findings could not be generalized to other populations, such as younger children with HIV and HEU children. This study did not include social and environmental factors that potentially could also have an impact on children’s behaviors and HIV treatment outcomes. Future studies could explore these factors in relation to HIV-infected children’s behaviors and health status. In addition, this study did not investigate HEU children. Future studies could explore the impact of HIV exposure on children’s health by specifying the three groups because HEU children are also a vulnerable group that may need attention for research and psychological interventions. Further, considering participants' capability of providing accurate information, we measured medication adherence using a survey question asking about missed doses in the past month. However, this self-reported method was susceptible to recall bias, also, this adherence measure might not fully reflect participants’ adherence status. Although MOS-HIV has not been validated in HIV-infected children, it has shown good reliability and validity in adults living with HIV/AIDS [
30]. In addition, the internal consistency of the self-reported conduct problems and peer problems subscales in this study was relatively low, which was consistent with previous studies that were conducted among Chinese children and in other cultures [
46,
47]. It could be explained by the small number of items for each domain; however, these items may represent more heterogeneous constructs than we intended to measure. Despite the low internal consistency of the two subscales, this scale has been widely applied in many cultures with different languages. In this sample, mother-to-child transmission is the major transmission route. Families and parents of our participants may encounter unique challenges relative to children’s care and medication utilization due to some other factors, such as parents’ HIV status, mental health status, general health status, poverty, stigma, death, etc. All these factors may have an impact on children’s health and HIV care. Therefore, in the survey for support sources, various sources of receiving support were included. Future studies that investigate HIV treatment outcomes, such as medication adherence may consider the potential impact of parental factors. Further, future studies could also consider investigating parental responses and views on children’s behaviors and emotional symptoms as complementary information to children’s self-reports.
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