This study has identified very important information regarding the predicters and time to treatment failure among HIV-positive children on antiretroviral therapy (ART), which can help planners and decision-makers undertake activities to prevent early first-line treatment failure.
There were 114 (21.2%) treatment failures among children who began ART from September 11, 2006, to September 10, 2021. Compared to the UNAIDS cut-off reference range of less than 10%, this rate of treatment failure was unacceptably high [20]. The most common type of failure was virological failure, followed by clinical and immunological failure. These results were greater than those reported for the different regions of Ethiopia, including Addis Ababa (14.1%) [21], the Amhara Regional State (12.19%) [20], and Jimma University Hospital (11.5%) [22]; moreover, the pooled prevalence of treatment failure was 15.3% [22]. Moreover, ART treatment failure among children reported in other parts of Ethiopia, including University of Gondar Hospital (18.2%), [23] Black Lion Hospital (22.6%)[24], and Fiche and Kuyu Hospitals (18.9%)[23], is consistent with these findings. This may be due to similarities in the study period and design. However, this percentage was lower than that in Ghana (29%), Tanzania (57%), Uganda (29%), and Mozambique (29%), according to previous reports[25]. This could be explained by the fact that the current study included children under the age of 15 years, but others up to the age of 18 years and the time to diagnosis of treatment failure were different; that is, at least 6 months were included in this study, but less time was included in the other studies.
In the present study, the first-line ART failure rate was 4.53 per 1000 person-months. This rate is greater than the 2.2 per 1000 person-months observed in the Amhara Region, Ethiopia [26].
WHO stage III and IV, poor adherence to ART, stunting, no change in regimen, and poor ART adherence were found to be statistically significant predictors of ART failure.
Children in advanced WHO clinical stages (stages III and IV) were three times more likely than their peers in WHO stages I and II to experience treatment failure during the commencement of ART, similar to the findings of other studies conducted in Mozambique and Uganda [20]. Children in advanced WHO clinical stages are more likely to have extensive immune suppression and a higher rate of comorbidities, which increases the chance of ART failure. Furthermore, children with advanced disease may experience drug side effects, particularly in the first six months, complicating disease progression even further [27].
Children with poor adherence to ART regimens had a 6.6 times greater risk of first-line ART failure than did their peers (AHR = 6.6, 95% CI = 4.11–10.66). Previous studies conducted in Ethiopia [28], Rwanda [29], Uganda [30] and Tanzania [31] reported similar results. This is because a high degree of sustained adherence is required to suppress viral replication and improve immunological and clinical results, lowering the likelihood of ARV treatment resistance and reducing the danger of HIV transmission. In contrast, poor adherence to antiretroviral therapy (ART) is common in the treatment of HIV-positive children and adolescents due to a variety of factors, including regimens for children, which often require the use of multiple pills with frequent dosing requirements, each with the potential for adverse effects and drug interactions, a limited selection of paediatric formulations, and poor palatability of liquid formulations. Adherence may also be influenced by a child's age and developmental stage, as this age group needs assistance from others to take medication on time and may have difficulty swallowing tablets [19]. Another possibility is that poor drug adherence leads to HIV-related viral resistance and, as a result, treatment failure. Furthermore, because children rely on their caregivers for their care, if the child's progress is poor, caregivers may experience hopelessness, carelessness, and loss as a result of the treatment cascade.
With respect to nutritional status, children with stunted nutritional status were 2.2 times more likely to develop ART treatment failure than were those with normal nutritional status. The findings of studies undertaken in Ethiopia and other African countries were consistent with the current findings[32–34]. This could be because stunted children may have had poorer baseline health and ART compliance than normal children. In reality, HIV affects nutritional status on its own, increasing susceptibility to the virus and hastening disease progression in malnourished children [21, 35]. Furthermore, stunted children may have had a simultaneous opportunistic infection that caused them to miss out on receiving their medications [36].
In addition, children whose regimens were not changed were 4.4 times more likely to experience ART treatment failure than were those whose regimens were changed. It is possible that the majority of previous regimens include adverse effects that lead to advanced disease and complications, which can ultimately lead to death. For example, AZT regimens can lead to anaemia, which exacerbates the progression of the disease [23]. This was further confirmed by the fact that the failure rate prior to 2019 was greater than the rate from 2019 onwards, and children who received NVP-based NNRT had a 2.72-fold greater chance of treatment failure than did those who did not receive nevirapine. This finding was supported by studies conducted in South Africa, [37], Uganda and Tanzania [31, 38]. This could be because nevirapine produces adverse symptoms such as rash, nausea, fatigue, fever, headache, vomiting, diarrhea, and abdominal discomfort, which can make it difficult to adhere to a treatment regimen and lead to treatment failure [25].
Finally, those children who were still treated based on the old guidelines were 1.5 times more likely to experience ART failure than were those who were treated based on the new guidelines. This result was supported by the comprehensive National ART Guidelines 2018. According to the guidelines, due to side effects and treatment failure, nevirapine-based regimens should be changed to DTG regimens containing drugs when the patient ages from 6 weeks to 10 years and the weight > = 20 kg[20]. However, among those children who developed treatment failure, only 37.2% changed their guidelines to new ones. These findings are consistent with the results of the change in regimen and nevirapine-based regimen use. Moreover, for those children with treatment failure, 71.1% were older than or equal to five years, and 73.3% had a viral load < 1000 copies/ml. These criteria can be used to guide the new guidelines even though they are not practical. This may be due to inappropriate training given for health professionals or drug shortages.