In 2019, the National AIDS Control Organisation (NACO) estimated about 20.52 thousand pregnant women to be infected with HIV annually (NACO 2019). The Prevention of Parent to Child Transmission (PPTCT) intervention aims to limit perinatal transmission by initiating ART during the antenatal period. Despite this, 3.98 thousand new infections in children aged below 15 were reported (NACO 2019). Vertical transmission is the most dominant mode of acquiring HIV infection in children and early initiation of antiretroviral therapy is vital in limiting the progression to AIDS (Haberer and Mellins 2009).
This cross-sectional study of 96 children on antiretroviral therapy was performed to analyse the adherence, safety and efficacy among children at a tertiary hospital in Mumbai. We used two methods to assess adherence to ART since there is no gold standard for the same. 89.6% of children (n = 86) enrolled in our study were found to have good adherence (> 95%) by the pill count method. On determining adherence by the caregiver recall method, we found > 95% adherence in all children. This difference in adherence obtained by two methods could suggest inaccuracies while using the caregiver recall method. Although the caregiver recall method is very commonly used, it has been known to be associated with recall bias (Vreeman et al. 2008). This could result in incorrect interpretation of the adherence unless combined with one of the more accurate methods of determining adherence. The adherence determined by the pill-count was taken as a closer approximate to the actual value of adherence. Rates of adherence can vary across centres due to different policies on provision of ART, availability of pre-ART counselling services and the access to an ART clinic. Our centre is in an easily accessible location, provides free ART and has a skilled team involved in counselling the patient prior to initiation of ART. This could explain the high levels of adherence in our study.
All children aged below 5 reported good adherence to ART. These children are completely dependent on their caregiver for regular intake of medication and a 100% rate of good adherence (> 95% of prescribed pills taken) reflects active participation of the caregiver and their understanding of the importance of early treatment. However, the association between age group and adherence to ART was not statistically significant in our study. Results from a similar study in Ethiopia showed statistically significant decrease in adherence as children grew older. This was explained by the fact that older children are often entrusted with the responsibility of taking their own medication and this may come at an age where they are not yet able to comprehend the value of adherence to long-term therapy (Dachew et al. 2014). This contrasts with a study in Kenya which reported higher adherence in older children (Wadunde et al. 2018). Higher adherence was attributed to an increased awareness among these children once they were disclosed with the status of being HIV positive. Bhattacharya et al., reported a significantly higher adherence in male children perhaps due to prevalent cultural norms that favoured the male child (Bhattacharya and Dubey 2011). We did not find a similar association between sex of the child and adherence to ART.
Children who were under direct care of a biological parent showed significantly higher rates of adherence. This emphasises the need for counselling services and regular monitoring of children who are not under direct care by their biological parents. Non-biologically related caregivers may often neglect the wellbeing of their children, and this could explain the poor levels of adherence.
Most children were diagnosed at stage 1 of HIV infection perhaps due to more awareness and early detection of HIV infection. The clinical stage of the infection is predictive of the CD4 count during recovery and children with a less severe clinical stage of HIV have been reported to have higher CD4 counts on follow-up (Barry et al. 2013). 91% of children in our study showed a decrease in clinical stage of the disease on follow-up, while the remaining did not show a change in the clinical stage of their disease.
Regarding a particular regimen of ART, adherence depends on the frequency of dosage, palatability, side-effects and dietary restrictions (Chesney 2003). Certain regimens that require a high frequency of dosage require the caregiver’s effort in ensuring doses are administered on time. However, side-effects and taste of a particular regimen play a part in how the child reacts to the regimen and such factors are not under the caregiver’s control. Syrups are the easiest form of medication to administer to children (Goode et al. 2003). ART medication in children should be in a form that is easy to administer or can be mixed with food without much aversion to taste. All children on EFV and SLN regimens showed > 95% adherence. This contrasts with the ZLN regimen which was associated with myelosuppression and resulted in > 95% adherence in only 88.9%. Zidovudine-associated myelosuppression requires close monitoring to facilitate transfusion in case of anaemia and to regulate dosage in case of neutropenia (Morales-Pérez 2021). Children who developed myelosuppression were switched to the SLN regimen. 8.3% of our cohort developed a skin rash due to nevirapine and were withdrawn from the drug immediately. Prompt discontinuation following development of cutaneous rashes is necessary to prevent the risk of progression to Stevens Johnson’s syndrome or toxic epidermal necrolysis (Fagot et al. 2001). Offering the caregiver medication-specific advice prior to initiation of ART and at regular intervals, either over a phone call or during their visit to the ART clinic can help address issues faced by them.
Unintentional non-adherence has been described as a lack of understanding of the importance of adhering to therapy (Iacob et al. 2017). Forgetfulness was the cause of poor adherence in four children. Caregivers of the other six children who were found to have poor adherence attributed this to being out of their hometown. Our ART clinic provides the necessary amount of medication for the month and these drugs can be administered at home under parental guidance. Thus, devising ways to tackle the problem of unintentional adherence can lead to significant improvement in adherence rates.
An optimum level of adherence at 95% was shown to be associated with significant virological death (Kim et al. 2018). In a similar study, 90.9% of children had an optimal adherence of > 95%. However, 15.4% of these optimally adherent children did not achieve viral suppression, possibly due to resistance to ART (Mehta and Ekstrand 2016). All children who had a decrease in CD4 count in our study were poorly adherent to ART. Apart from optimum adherence, an improved CD4 count following ART depends on the child’s age and the clinical stage of the infection at initiation of treatment wherein early diagnosis and initiation of treatment corelates to an increase in CD4 count (Birhan et al. 2020). This increase was found to be maximum during the first 3 months of therapy (Birhan et al. 2020). Thus, offering regular counselling services to caregivers at the initial phase of treatment can improve the overall outcome. Support services offered to caregivers in the form of text messages have been shown to increase the rate of adherence to ART (Kaufmann et al. 2003).
Our study is limited due to its cross-sectional design, wherein children underwent a single assessment to determine their adherence to ART. This could be inaccurate since adherence to a chronic illness like AIDS is a process that may change over time and a better estimate could have been obtained by assessing adherence at regular monthly intervals. In addition to this, we did not account for the children who were lost to follow-up and only included children who visited the ART clinic during the study period. We also did not study the relationship between adherence and side- effects of a particular regimen of ART. Analysing specific factors pertaining to each regimen that affect adherence could help identify problems and implement strategies to improve adherence.