Magnitude and associated factors of virological failure among children on ART in Bahir Dar Town public health facilities, Northwest Ethiopia: a facility based cross-sectional study

Globally, human immunodeficiency virus (HIV) is a major public health problem and associated with a range of short-and long-term consequences. Approximately 1.8 million children (age < 15 years) were living with HIV globally in 2018 [1]. Sub-Saharan Africa (SSA) suffers from the global burden of HIV- infection, with nearly 70% of the world’s HIV/AIDS-infections and deaths occurs in this region [2]. Based on Ethiopian public health institution HIV related estimates and projections about 704,454 populations were living with HIV in 2020. Of these 41,265 were children. Beside that 20,130 were newly infected and 7684 were died with HIV related illness [3].

The goal of antiretroviral therapy (ART) is to suppress viral replication and reduce HIV associated mortality among infected children. Thus, monitoring people on ART is important to ensure treatment success, identify adherence problems, and determine whether ART regimens should be switched in case of treatment failure (TF). Treatment failure can be assessed in three ways: clinically, immunologically, and virologically, which offers early and accurate indication of treatment failure [4].

The World Health Organization (WHO) recommends routine annual viral load monitoring for all patients on ART, as the most accurate and preferred method to measure treatment response [4, 5]. In 2014, the Joint United Nations Program on HIV/AIDS (UNAIDS) and partners launched the three 90–90–90 targets, having 90% of patients on ART with VLS is the third “90” targets. Adherence counseling, early detection of TF, and appropriate switching to second-line therapy are key strengths of a viral load monitoring [4, 6]. Likewise, the Ethiopian government launched different strategies, programs, and policies that provide aspiring and far-reaching goals on prevention, treatment, health coverage, and access to affordable medicine for HIV/AIDS patients like Sustainable Development Goals (SDGs) [7]. Ethiopia has adopted the UNAIDS 90–90-90 HIV treatment target and has developed HIV/AIDS prevention and strategic treatment plan, which has been implemented since 2015 [5]. Ending the AIDS epidemic by 2030 is the aim of this strategic plan in line with the three 90’s targets.

In Ethiopia, few studies have been conducted on TF by considering previous guidelines [8]. However, some critical factors such as HIV status disclosure, level of Hgb, history of ART interruption, CD4 cell counts, and caregiver’s HIV status, which contribute to VF occurrence, were not included. Furthermore, the previous studies were done at the referral hospitals with diverse health workers to manage cases [8, 9]. Despite hospitals and health centers are using the same ART guidelines, this study included health centers as they cover most health facilities that have been giving pediatric ART services [5].

This facility-based cross-sectional study found that the magnitude of virological failure among HIV-infected children was 14.8% (95% CI: 11.5–19.3%). This finding is in line with the magnitude of virological failure reported from Ghana (15.7%%) [11], South Africa (19.3%) [12], and Malawi (16%) [13]. Conversely, this finding is lower than studies conducted in Cameroon (30.6%) [14], Kenya (43.1%) [15], Tanzania (25.4%) [16], and Malawi (66%) [17]. The possible sources of variation in the prevalence rate of virological failure might be due to the differences in sample size, study period, the variability in virological failure measurements, and the difference in diagnostic capacity. As an example, a Tanzanian study included only 206 participants. Regarding variability in virological failure measurements, a studies done in Malawi and Cameroon used a single plasma viral load above 1000 copies/ml, and 200copies/ml to diagnose virological failure respectively [14, 17], whereas this study used two consecutive plasma viral load 1000 copies/ml and above. The other possible justification for the discrepancy could be due to the difference in study period as there were changes in treatment guidelines over time. An additional possible explanation might be the difference in diagnostic capacity between study settings or different methods used to retrieve and analyze it.

We found that different factors were significantly associated with the occurrence of virological failure. In this regard, younger ages (age ≤ 5 years) were more prone to develop virologic failure. This finding is in agreement with other previous studies done in Swaziland [18], African and Asian children [19], Tanzania [20], and Zimbabwe [21]. This could be explained by the fact that children initiating ART at their younger age are more likely to have an immature immune system, which causes rapid disease progression contrasted with a comparative group [22]. Additionally, HIV-status disclosure is the most important factor for positive treatment outcomes [23, 24]. However, in our study, HIV-status disclosure among children aged less than 10 years was very low. Furthermore, unlike younger children, older children might have the opportunity to get information about HIV/AIDS in school, enabling them to adhere to their treatment. On the other hand, in younger children, their drug has mainly been given by caregivers, and they could miss it.

However, this finding contradicts with researches done in Cameroon [14], and Tanzania [25] suggesting that older age at ART initiation was significantly associated with high virological failure. The possible explanation for the above noted differences could be due to the differences in inclusion criteria. For example, a study done in Cameroon included participants age lower than 18 years, whereas our study included children under 15 years.

This study also revealed opportunistic infections during follow-up were strongly associated with the occurrence of virological failure. This result is concordant with other reports from Tanzania [20] and Kenya [26], which demonstrated that co-morbidities such as TB (one of the opportunistic infections) were associated with the occurrence of virological failure. This is well-known that co-morbidities such as TB weaken the immune system among patients and rapidly increase HIV disease progression to its advanced stage. Additionally, although ART needs a lifelong commitment for its effectiveness, HIV-related co-morbidities could prohibit patients from getting their regular ART follow-up and treatment intake. There is an inverse linkage between viral replication and the efficiency of the immune system, resulting in acquiring virological failure [5, 27]. Finally, HIV-infected children with co-infections are at high risk for drug burden and drug-drug interactions which might lead to poor ART adherence and treatment failure, especially anti- TB- drugs [28].

History of ART treatment interruption/discontinuation was also significantly associated with the occurrence of virological failure. This is because ART suppresses the viral replication resulting in boosting the patient’s immunity, decreasing the incidence of OIs, and reducing the viral load [29]. Moreover, as ART helps boost HIV-infected individuals’ immunity, drug interruption could be associated with a decreased efficiency of the immune system and increased drug resistance risk. As a result, patients lose their ability to suppress viral replication and reduce viral load, finally leading to virological failure [30, 31]. In addition, this is due to the fact that interruption of antiretroviral therapy (ART), opportunistic infection, and WHO clinical stage are highly interrelated risk factors for treatment failure. As patients interrupt regular follow-up and discontinue taking drugs, their immune status becomes compromised. This implies, there is a high chance of acquiring opportunistic infections and increase the rate of viral replication as well, which leads to disease progress/advanced clinical stage and virological failure [29, 32].

This study also found that children classified as advanced WHO clinical staging (stage III and IV) were more likely to develop virological failure. This finding is in agreement with studies reported from Uganda [33] and Swaziland [18]. This might be due to the fact that children presenting with advanced WHO clinical stage at ART initiation are at higher risk of OIs, especially TB. The presence of OIs during ART initiation increase pill burden, which results in drug-drug interactions, and ultimately leads to treatment failure and early mortality. Studies suggested that HIV-infected individuals treated with anti-TB medications usually experience drug toxicity as compared to HIV-uninfected individuals [34, 35].

Finally, children who had fair/poor ART adherence level were also positively associated with virological failure. This finding is supported by studies conducted in Uganda [33], Tanzania [36], and Gabon [30]. If HIV-infected individuals failed to take their medication regularly and daily, they are at higher risk to developing drug resistance. This resulted in experience virological failure [29].

This study demonstrated that, there was a high magnitude of virological failure among HIV positive children compared to the current Ethiopian ART guidelines target (not more than 10%). Children with poor/fair ART adherence level, history of ART treatment interruption, advanced baseline WHO clinical staging (stage III and IV), younger age, and opportunistic infections were found to be factors significantly associated with the occurrence of virological failure.