Strategies towards Empowering Nurses on the Rational Use of Antiretrovirals in Children Initiated and Managed on Therapy in Rural Primary Healthcare Clinics of South Africa

Abstract

HIV has affected the health and welfare of children and undermined the success of child survival in some countries. The introduction of antiretroviral therapy (ART) in managing HIV is one great public health success story. ART has commanded increased survival for people living with HIV (PLHIV). Barriers to achieving ART outcomes in children have been simplifying the prescribing process for non-paediatricians, such as medical doctors and nurses familiar with prescribing ART for adults but involved in treating children, particularly at the primary health care level. And the lack of appropriate antiretroviral formulations for children. The calculation of individualised doses for liquid oral ARVs for children at each clinic visit is considered complicated and time-consuming. ART failure among children seems to be an under-recognised issue, and adherence to treatment guidelines is reported to be a challenge among nurses caring for children and PLWHIV. Rational medicine use is essential to ensure the success of pharmacologic interventions. The attainment of ART goals depends on the effective use ARVs as recommended in guidelines. It is pivotal that nurses be empowered with strategies aimed at promoting the rational use of antiretrovirals.

1. Introduction

The concept of rational use of medicines is old. It dates to 300 BC when the physician Herophilus said that “medicines are nothing in themselves but are the very hands of God if employed with reason and prudence” [1]. For many years, the rational use of medicines has been regarded as one of the critical principles of effective and quality health care [2, 3]. In 1985, the World Health Organisation (WHO) convened an expert meeting on the rational use of drugs, from which the rational use of drugs was defined as a contextual picture where “Patients receive medications appropriate to their clinical needs, in doses that meet their requirements, for an adequate period, and at the lowest cost to them and their community” [4]. The World Bank also defines the rational use of medical care as two fundamental principles, such as using medicines in accordance with scientific evidence for efficacy, safety, and compliance as well as the cost-effectiveness of the medicines in use within the constraints of a particular health system [4, 5].

Although the World Bank definition considers the financial capacity of medicine use in different countries, the WHO advocates using medicines at the lowest possible cost, regardless of the healthcare system [5]. The WHO and World Bank definitions are primarily based on therapeutic and medical perspectives. Reasonable use of drugs can also be seen from the consumer or patient’s point of view. What is considered beneficial from a medical point of view may be regarded as unreasonable by the patient and vice versa [6]. From a medical point of view, improper use of drugs can begin in one of four major stages (Figure 1) of the medicines use cycle [2].

Figure 1.

Medicine use cycle.

Even though half of the patients take almost half of their medicines correctly, half of all medicines are inappropriately used worldwide. The inappropriate use of medicines leads to resistance development, medication therapy problems, and increased medicine and treatment costs [7]. Therefore, both medical and patient perspectives need to be considered to gain a complete understanding of the rational use of drugs.

2. History of antiretroviral therapy in South Africa

When the South African national Antiretroviral Therapy (ART) Program was launched in 2004. It was utterly dependent on the hospital’s HIV clinic, where ART services were provided exclusively by medical doctors [8, 9, 10]. This means that ART and care at SA at the time were limited to several selected accredited health clinics due to the presence of doctors in these clinics. Most public clinics were run and operated by nurses, so ART services were only seen in hospitals. The doctor then managed the ART program, performed a health examination, and initiated and prescribed treatment for the patient in need. Nurses were not allowed to treat HIV patients or prescribe or administer ART [10]. This practice resulted in the overcrowding of hospital facilities following an increasing demand for HIV care with limited personnel. Consequently, poor management of patients on ART necessitated the decentralisation of services to PHC clinics, rendering nurses essential to managing patients living with HIV [11, 12, 13, 14].

Hence, managing the HIV/AIDS pandemic made SA struggle to reply to the troubling impact of HIV/AIDS in conjunction with upholding its democratic mandate to give equitable access to health services progressively. These challenges forced the government to rethink and reorganise its health resources and systems because of the reconsideration of the roles and responsibilities of nurses within the management and care of chronic and complicated diseases [15]. For example, in April 2010, ART was granted a presidential mission stipulating that ART is currently available in all 5500 South African public clinics. It required SA to revise the HIV treatment guidelines in 2010 and request nurses in primary care clinics to enrol for the Nurse-Initiated-and-Managed Antiretroviral Therapy (NIMART) training [16]. The mandate also meant that nurses should be trained to prescribe and treat patients with ART. NIMART has changed the role of HIV treatment and management.

The spread of HIV has led to innovations in the areas of nurse training, job shifts, retention, and practice. This expansion of HIV services was designed to meet the urgent needs of prevention, care, and treatment and embrace the vision of decentralised HIV services to PHCs [15]. Van Damme et al. [17] emphasise that the adoption of ART to reasonable levels, like primary health care, has increased ART access for PLHIV.

Following the implementation of task shifting, it was reported that a total of 2552 public clinics were involved in initiating and caring for patients on ART by April 2011. By March 2015, this number had reached 3591 public clinics [18]. As the numbers grew, training needed to be widened and improved since NIMART required nurses to assess, diagnose, and manage patients with HIV. Nurses, therefore, need to be equipped with skills such as history taking, physical assessment, interpretation of laboratory results, and knowledge about the pharmacological interaction of antiretroviral drugs [19]. The main reason for this integration approach was that in SA, PHC is an identified level of care that reaches most South Africans. Therefore, it is a relevant platform for the ART programme to reach all those in need [20].

Crowley and Stellenberg [21] cautioned that, even though HIV services are a decisive part of PHC, public clinics need to be sufficiently equipped for them to be able to provide quality HIV services to children on ART. This seems to be a global challenge in that Portillo et al. [22] highlight a San Francisco reality that the increasing demand for PHC services and the current healthcare personnel shortage is foreseen to cause compelling reductions in the number of healthcare professionals who are competent to provide HIV care. Moreover, Meyers et al. [23] had foreseen this situation and said that “there has been a dramatic increase in ART access for HIV-infected children in SSA”. However, the availability of adequate care and treatment programs remains limited. Hence, it is essential to note that the decentralisation of services to rural PHC facilities without the provision of sufficient Human Resources (HR), as well as constant support, could compromise the quality of care provided to patients at this level with long-term repercussions for reaching the National strategic plan (NSP), strategic developmental and global health goals.

Meyers et al. [23] emphasised that essential HIV care, treatment services, and managerial support are vital components for ensuring quality services. Furthermore, they highlight that the provision of ART at the PHC level should be supported with human resources and the implementation process of comprehensive models to decentralise HIV care effectively. In the era of Sustainable Development Goals (SDGs), the UNAIDS set countries the ambitious “90-90-90” target of eradicating global infection with HIV by 2030. This required that by 2020, 90% of people living with HIV would know their status, 90% of whom would be on ART, and 90% of the latter would be virally suppressed [24].

3. HIV care in children and the prevention- of -mother- to- child- transmission

The SA programme for the prevention- of -mother- to- child- transmission (PMTCT) of HIV has, in recent years, achieved noteworthy successes in ensuring good outcomes for pregnant women living with HIV and reducing the risk of vertical HIV transmission to their children [25]. Despite having a persistently high antenatal HIV prevalence of around 30%, South Africa (SA) has made excessive developments in reducing the vertical transmission of HIV in children, especially in their first two months of life, from around 23% in 2003 to about 0.7% in 2019 [26]. Improving ART access during antenatal care has contributed significantly to this success. The integration of ART initiation into Antenatal Care (ANC) is associated with higher levels of ART initiation during pregnancy [27]. Still, it has led to an increase in the relative proportion of vertical transmissions due to breastfeeding in the first six months post-delivery [26].

4. Complexities in the management of children on antiretroviral therapy

The introduction of the NIMART programme in rural clinics brought the emergence of new challenges regarding prescribing and dispensing ART by nurses [28]. The Millennium Development Goals (MDGs) era also confirmed that children living with HIV continue to have less access to HIV services than adults [24]. Issues of ARV tolerability and access to formulations appropriate for children also remain. For instance, the Lopinavir/ritonavir (LPV/r) formulation is very unpleasant to taste. Infants often tend to tolerate it when their taste buds are still undeveloped but spit or vomit it out as the taste buds develop and they grow older [29, 30]. In South Africa, only in 2020 did the LPV/r pellets become available in the state and private sectors. These pellets are developed to overcome challenges with administration and storage experienced with the previously available tablet and syrup formulations for paediatric HIV patients [30, 31].

5. The goal of antiretroviral therapy in children

ART aims at reducing the rate of replication of HIV and breaking its progression into AIDS [32, 33, 34, 35, 36]. The use of ART is the basis of clinical interventions that can be used to prevent the transmission and progression of HIV infection in people living with HIV/AIDS. Even though ART does not destroy the virus and cannot cure HIV or AIDS-related illnesses, it significantly reduces the viral load. It slows disease progression, thus increasing the life expectancy and quality of life of PLHIV [37]. Furthermore, when effectively used in children, ART has been shown to improve growth and virologic and immune responses [38, 39, 40, 41, 42]. Mortality due to HIV infection in children has meaningfully decreased in the era of effective ART [43, 44]. Quality of life is an essential ART outcome [45] in developing countries that have not been solved yet. The range of HIV/AIDS problems measured by the number of affected children is extensive [46].

6. Challenges with antiretroviral therapy

A noted obstacle towards achieving widespread paediatric ART coverage has been the simplification of the prescribing process for non-paediatricians, including medical doctors and nurses who are more familiar with prescribing ART for adults but also involved in initiating and managing children on ART, particularly in rural primary care levels of South Africa [31]. The calculation of individualised doses for children, especially for liquid oral ARV formulations for infants or young children at each clinic visit using the current weight or body surface area, is also observed to be a complicated and time-consuming process for nurses in resource-limited settings [31, 47]. The development and updating of an integrated weight-based ARV dosing chart for children based on WHO guidelines and adapted for the ARV formulations available in South Africa has contributed to building confidence among prescribing clinicians and pharmacists and helped facilitate children’s access to ART [31].

6.1 Adherence to ART in children

The main goal of antiretroviral therapy is to reduce the viral load (VL) in the blood to undetectable levels. Over the decades of ART, various scientists have determined that adhering to this treatment is essential for patients to experience the full benefits of ART, which include the overall and permanent suppression of viral replication, reduced destruction of CD4 cells, the prevention of viral resistance, the promotion of immune reconstitution, and a decreased disease progression. ART improves the prognosis of people living with HIV and reduces HIV-related morbidity and mortality, as well as the development of other opportunistic infections [48, 49, 50]. DiMatteo [51] defines this as the extent to which a patient’s drug-consuming behaviour aligns with the doctor’s recommendations. Although essential, ART compliance is often challenging for people treating ART, especially children. Factors affecting a children’s ART compliance include (i) the caregiver, (ii) the child himself, (iii) the prescribed medication or treatment, (iv) socio-economic status, and (v) the provision of services [51, 52, 53, 54, 55]. The degree to which patients are compliant with their treatment regimen is an essential determinant of clinical success [56, 57].

There is no generally accepted measure of ART compliance, and each method has various strengths and weaknesses, as well as cost, complexity, accuracy, accuracy, aggression, and bias. Therefore, developing real-time ART adherence monitoring tools can change the development of new preventive strategies to improve adherence. Ultimately, applying these strategies may prove to be the only cost-effective way to reduce morbidity and mortality in individuals and reduce the likelihood of HIV transmission and the emergence of resistance in the community [58].

6.2 Medication errors

Aronson has since 2009 defined medication errors as a failure in the treatment process that leads to or has the potential to harm the patient. Furthermore, he emphasises that medication errors can take place;

1. Whilst deciding which medicine and dosage regimen to use. These are often referred to as prescribing faults, and they encompass irrational, inappropriate, and ineffective prescribing, under-prescribing, as well as over-prescribing,

2. When writing the prescription (prescription errors),

3. During manufacturing of the formulation (wrong strength, contaminants, or adulterants, wrong or misleading packaging),

4. Whilst dispensing the formulation (wrong drug, wrong formulation, and wrong label),

5. During administering or taking medicine (wrong dose, wrong route, wrong frequency, and wrong duration),

6. Whilst monitoring therapy (failing to alter therapy when required, erroneous alteration).

These errors can be categorised with the help of psychological classifications such as knowledge, rules, behaviour, and memory-based errors. Dosing mistakes can sometimes be serious, but often they are not trivial. However, system failures that lead to minor errors can later lead to fatal errors, so it is essential to identify them. Velo and Minuz [59] predicted that bug reporting should be encouraged by creating an impeccable, non-immunity environment. In addition, prescription mistakes are irrational, inappropriate, and ineffective. There are also recipe spelling mistakes, including the indecipherability of the written recipe. Avoid dosing mistakes in balanced prescribing, that is, the use of drugs adapted to the patient’s condition and dosages that optimise the ratio of benefit to harm within the uncertainty associated with therapeutic decisions.

In clinical practice, the separation of prescribing and dispensing activities is considered a “safety mechanism to ensure an additional independent assessment of the proposed therapy before the patient begins treatment” [60]. In some settings, such as rural areas with limited health personnel [61], dispensing may be carried out by the prescriber, such as dispensing nurse(s). This is considered “non-ideal and may promote irrational prescribing, especially if the prescriber stands to gain financially” [62].

When the prescribing and dispensing functions are separated, proper therapeutic knowledge of the dispensing process is essential to check the prescribing gap and provide the prescriber with necessary recommendations or interventions. Therefore, contact between the prescriber and the patient is important because it can significantly impact the patient’s medicine use practice. For example, compliance may improve only if the patient understands the importance of taking the medication, can follow the instructions appropriately, and is aware of the risk of non-compliance [63, 64].

On the other hand, the WHO advocates that “the rational dispensing principle should be followed to ensure that patients receive adequate information regarding the use of dispensed medicines to achieve the desired benefits. For instance, if dispensing practices such as counting, packaging, and labelling is poorly executed; they are likely to impact the patient’s confidence in the dispensed products, and subsequently compliance to therapy” [65, 66].

7. Healthcare professionals’ compliance to treatment guidelines

The appropriate use and monitoring of ARVs have resulted in the enhancement of patient’s quality of life [67]. The implementation of task-shifting in South Africa and the decentralisation of ART [68] brought forth noticeable evidence of improved health outcomes, quality of care, and patient satisfaction for PLHIV [69, 70]. In South Africa HIV treatment guidelines, standard treatment guidelines and essential medicine lists are in place as a monitoring and support tool for healthcare professionals to ensure that they appropriately prescribe medicines and can provide good quality care to PLWHIV. There is also a recent (2019) South African National Guideline for the Prevention of Mother-to-Child- Transmission outlining three major strategies for programme improvement. These strategies aim at

1. “the prevention of primary HIV infection and unintended pregnancies in women of childbearing potential,

2. the improvement of maternal viral suppression rates at delivery and in the post-delivery period through potent, well-tolerated antiretroviral regimens, strategic use of maternal viral load monitoring, linking of mothers to post-delivery HIV care, and integration of mother-infant health care, and

3. the provision of enhanced prophylaxis to infants of mothers with elevated HIV viral loads in the breastfeeding period, while every effort is made to regain maternal viral suppression” [26].

Patient safety is a strategic goal and a central value in nursing practice. It is provided through an error-free medication administration which is essential towards achieving positive patient clinical outcomes for patients. In practice, there are therefore a set of guidelines that nurses are required to follow to ensure patient safety. Even though the nurses’ adherence to treatment guidelines and factors associated with non-adherence to treatment guidelines among nurses remain under explored [71, 72]. Studies demonstrate a suboptimal adherence to guidelines by all prescribers, and a need for training on the use of these guidelines as well as improved monitoring of compliance at PHC level has been identified [71, 72, 73].

8. Strategies for addressing the irrational prescribing of medicines

Generally, the irrational prescribing of medicines is considered a “disease” that is difficult to treat even though it is possibly preventable [74]. Therefore, there are several strategies that are aimed at changing patients and prescribing behaviour to encourage the rational prescribing of medicines. These strategies can generally be grouped into targeted or system-oriented approaches [2]. Targeted methods include educational, business, and system-oriented strategies include regulatory and economic interventions [2, 74, 75]. Educational interventions are often aimed at persuading or informative, including printed matter, seminars, or face-to-face contact [76].

Inappropriate medicine management occurs at all levels of the healthcare system, both in hospitals and primary health care. The factors influencing the irrational use of medicines are usually very complex. They are associated with the attitudes of prescribers who are often convinced of the effectiveness of a particular therapy without considering other alternatives, too much staff responsibilities, patient’s pressure on the use of a specific drug, lack of knowledge in the field of pharmacoeconomics, and others [77].

According to Wettermark et al. [78] educational interventions can affect the knowledge and awareness of prescribing physicians. Still, their effectiveness in behavioural change remains modest when not combined with other strategies. On the other hand, managerial techniques are specially aimed towards guiding practice. Such managerial interventions that can be hired consist of monitoring, supervision and feedback, the usage of a restrictive drug treatments list, drug utilisation reviews, or the usage of based prescription forms [75]. An example in this case is the “Swedish Wiselist”. This is the Essential Medicines List (EML), which adheres to only 200 medicines to increase physician familiarity with quality medicines and reduce costs, complemented by regular medical oversight to specialists [79]. Economic strategies, on the other hand, aim to promote positive financial incentives while eliminating the awkward incentives of prescribing physicians [80]. Embrey and Hogerzeil [2, 75] say that economic interventions could include introducing significant changes to the healthcare provider’s reimbursement system or banning prescribing drug sales.

In South Africa, to meet the basic constitutional human rights to health care, the new government commissioned a committee that specifically looked at medicine issues, this gave rise to the National Drug Policy (NDP) of 1996. The aim of the NDP is to address deficiencies such as the irrational medicine use, inaccessibility to medicines and cost-ineffectiveness treatment, and inefficient procurement and logistic practices to “ensure an adequate and reliable supply of safe, cost-effective drugs of acceptable quality to all citizens of South Africa, thereby promoting the rational use of drugs by prescribers, dispensers, and consumers”. The NDP allowed for the provision of the Provision of the EML guided guided by the Standard Treatment Guidelines (STGs) through the National Essential Drugs Programme [81].

For the intervention to be very effective, it should be targeted at the clinic or prescribers who have the utmost need for improvement, with a particular focus on the identified prescribing behaviours [2, 75]. In some cases, several interventions may often be required to make the necessary changes. Again, it is worth noting that the efforts to promote rational medical care and prescribing should be multifaceted, including the address of aspects of patient and community behaviour [82, 83]. The six steps method of pharmacotherapy education promoted by the WHO (see Figure 2) need to be executed in every medical and nursing curriculum “as part of an integrated learning program which has positive effects on medical students’ knowledge of basic and applied pharmacology, pharmacotherapy skills, and satisfaction and confidence in prescribing.” [84].

Figure 2.

Rational ARV prescribing cycle (adapted from the WHO-6-step of rational prescribing a guide to good prescribing).

9. Strategies for promoting the rational use of antiretroviral therapy

Failure of ART in children is an underestimated problem and is not adequately addressed by paediatrics and HIV treatment programs. The failure rate of paediatric ART in facilities with limited resources ranges from 19.3% to over 32%, so a comprehensive analysis of the causes of failure and an approach to addressing impaired adherence to treatment are urgently needed [85, 86].

Studies by Davies et al. [87] and Bunupuradah et al. [88] indicate that a high proportion of virological failures were observed in children in an established HIV primary care environment. These studies also found that the average age at which ART began in this cohort of primarily vertically infected children was 3.4 years, and the need to identify HIV-infected children early is latent. It suggests that you are missing out on the opportunity for a typical diagnosis. In addition, one-third of these children are said to have never achieved virological suppression since they were initiated on treatment. An inadequate system can explain this persistent viremia in the clinic to find a failed child or the lack of clinician knowledge or convenience to manage high viral loads. This is well reflected in the proportion of children (80%) who remained unchanged despite long-term antiretroviral therapy failures. One-fifth of patients aged 10–15 years were not fully disclosed at the start of the study, and this is a known risk factor for ART failure in children [87, 88].

These researchers also emphasise that VL testing in children on ART in resource-constrained environments should be prioritised over monitoring CD4 cell counts to reduce the time it takes for treatment to fail. They also suggest that this facilitates the appropriate conversion of children to secondary ART therapy and minimises immunological disorders. In addition, clinicians need to understand that the most important factor in good paediatric HIV management is achieving reasonable compliance [89]. Furthermore, they point out that easier ways of supporting adherence are very important in frequently visited clinics. This has been shown to significantly improve the quality of patient support that children and their caregivers receive. It is crucial for the nurses to keep in mind that adherence support should not be initiated when a child has a high VL. Very often, proper basic counselling on adherence is not provided until the child fails treatment, so once the child reaches a developmental milestone, proper counselling should be initiated and reassessed at the beginning of ART. Regular and continuous counselling is essential for paediatric patients, as the psychosocial situation of paediatric patients often changes and new barriers to adherence usually arise [90]. Providing paediatric antiretroviral care, particularly at PHC clinics, has distinct obstacles. One of these is a shortage of staff, which includes staff that is comfortable dealing with children [91]. Paediatric ART failure is an under-recognised issue that receives inadequate attention in the field of paediatrics and within HIV treatment programmes. With paediatric ART failure rates ranging from 19.3% to over 32% in resource-limited settings, a comprehensive evaluation of the causes of failure, along with approaches to address barriers to treatment adherence, is urgently needed [90].

In summary, one-third of children aged 0–19 in two HIV clinics with expanded primary care failed to achieve antiretroviral therapy, and 33% did not achieve virus suppression after the initiation of ART. Hence, by addressing the core deficiencies in paediatric HIV care, such as insufficient early diagnosis of HIV-infected children, lack of VL monitoring and clinician comfort in responding to high VLs, and the unstructured and inadequate adherence counselling, we will start to achieve durable VL suppression in children and control this silent epidemic [91]. This will help HIV/AIDS programmes to achieve long-lasting VL suppression within the paediatric HIV population and curb this silent epidemic. An effective response to the challenges of HIV treatment failure in LMICs must include reductions in the cost of second-line agents [92].

The strategies should be comprehensive, evidence-based, and focused on the rational long-term use of ART in children and adolescents [93, 94, 95]. Although early mortality and retention in care has been identified by different scholars as early as the year 2002 to be remaining as a significant challenge in HIV programmes, the majority of reports from low- and middle-income countries (LMICs) had in the past decade shown encouraging immunological, virological, and survival outcomes [96, 97, 98, 99, 100, 101, 102, 103], with lower than expected reported rates of switching to second-line ART regimens [104, 105], and this was back then attributed to being in part due to actual rates of treatment success, but mainly because of the limited access to both virological monitoring and the unavailability of second-line antiretroviral drugs [105]. In a study by Orrell et al. [106], clinicians were found to be reluctant to switch treatments due to the cost of the regimen, the complexity of the regimen, the inconvenience, and the lack of subsequent treatment options. With the maturation and expansion of the cohort and increased access to virological monitoring and second-line treatment, an increased failure rate of diagnosed treatment and a switch to second-line treatment were expected [107]. This is because the cost of second-line treatment is higher than the cost of first-line treatment. These increases are due to the HIV treatment programs [108, 109, 110]. Elliott et al. [111] identified the need for rational ART use in LMICs, which relies heavily on accurately identifying medical malpractices and optimising the timing of the clinician’s switch to alternative therapies. In addition, consider various factors such as availability, risk, and benefit substitution to assess the risk of HIV drug resistance and reduced therapeutic efficacy, immunological and clinical progression, and inappropriate early switching of patients. Rivera et al. [112] indicated that HIV resistance develops due to low ARV drug levels because of several factors and variations in drug absorption and metabolism and noncompliance owing to adverse effects or a poor understanding of the importance of the medication. The monitoring of VLs must guide effective treatment [113]. Hence, the recommendation is that the following two conditions are adhered to: Firstly, adequate plasma drug levels must be maintained as results may be inconclusive if adherence is not satisfactory or if the prescribed regimen has not been followed. In addition, the quality of drugs, bioavailability, and drug-drug interactions can affect the outcome. Secondly, the availability of alternative medicines must be assured [113].

10. Adherence to HIV treatment guidelines

The appropriate use and monitoring of ARVs have resulted in the enhancement of patient’s quality of life. However, Elliott et al. [111] contend that the complexity of treatment regimens, over and above a multitude of factors such as drug intolerance, poverty, and the level of education of patients, directly influenced the lack of adherence. This also directly influences resistance and treatment failure. Hence, the rational use of ART in LMICs is critically dependent on clinicians’ precise detection of treatment failure [111]. The proper use and monitoring of ARV has dramatically improved the patient’s quality of life in recent years. However, the complex nature of these therapies, in addition to various factors such as drug resistance, socio-economic status, and the level of patient education, can reduce patient compliance and increase resistance and treatment failure potential. On the other hand, prescribing errors in ART management are said to be common in inpatients [114].

The rational use of ART in LMICs relies heavily on the accurate detection of TF and optimisation of the timing of switching to alternative therapies. Monitoring and switching strategies aim to balance the risk of HIV drug resistance with reduced efficacy of second-line treatment, immunological and clinical progression, and inappropriate early switching. Current and future status of alternative therapies and general medicine availability [111].

There is no well-established link between antiretroviral usage and the development of virological, treatment, and immunological failure, except that virologic failure is highly dependent on the patient’s adherence to the prescribed antiretroviral treatment. To the researcher’s knowledge, the inappropriate use of ARVs by prescribers is a topic that has never been explored, especially evaluating its impact on the clinical outcomes it might pose to children on ART. When looking at antibiotics as an almost similar class of drugs to ARVs, the literature highlights that the well-established link between antimicrobial usage and the development of resistance emphasises the importance of developing strategies to improve antimicrobial prescribing. It further highlights the possible reasons for inappropriate prescribing: lack of education, misinterpretation of results, prescribing etiquette, and medication errors. These contribute to the increase in morbidity and mortality, the development of antimicrobial resistance, and healthcare costs to such an extent that studies have proven the importance of antimicrobial prescribing [115, 116, 117].

Similar to antimicrobials, there is no established nor existing reference for measuring the appropriateness of ART use. [118] highlight that compliance with local, national, and international guidelines as the standard for appropriate therapy is increasingly utilised to reduce subjectivity. Moreover, evaluating compliance to treatment guidelines provides a reproducible method for large-scale evaluations across multiple facilities, especially when sharing similar treatment guidelines such as the consolidated national guidelines for managing HIV/AIDS [119].

The appropriateness of every antiretroviral prescribed can be assessed according to classic criteria established for antimicrobial evaluation by Kunin, Tupasi and Craig [120] (see Table 1). Even though this criterion seems outdated, it has since been used and relied upon by many established researchers in appropriate antimicrobial use; for example, researchers such as Dailey et al. [121], Bishara et al. [122] and van Bijnen et al. [123] have all conducted their studies following this criterion depicted in Table 1.

Action	Description
Appropriate indication	Correct choice in presence of one or more of the following): Tuberculosis Severe malnutrition Neonates <28 days of age Infants weighing <3 kg Hepatitis
Correct choice of antiretroviral drug and correct administration and dosing instructions
Inappropriate indication	Inappropriate decision; Selected regimen not suitable for the patient’s age Selected regimen not suitable for the patient’s weight Inappropriate choice; Different ART needed, than what is prescribed: unnecessary divergence from HIV/AIDS treatment guidelines regimen spectrum was overly broad regimen spectrum was not broad enough Incorrect use; Incorrect dose Incorrect dosing frequency Incorrect route of administration Incorrect duration of therapy Incorrect quantity dispensed Insufficient information; No information on whether ART switching was necessary Insufficient clinical information on whether ART switching was needed Inappropriate indication; Inappropriate decision on regimen selection Inappropriate choice of antiretroviral(s) Incorrect use of antiretroviral(s)

Table 1.

Criteria for categorising the appropriateness of ART use in children (adapted from Kunin et al. [120]).

11. Good medical record-keeping in HIV/AIDS management

Inaccuracy in prescription writing, poor legibility of handwriting, the use of abbreviations and incomplete prescriptions contribute to the poor keeping of medical records. For example, omitting the total volume of the prescribed syrup or solution or the duration of the prescribed medicine can lead to misinterpretation by healthcare personnel. This can result in medicine dispensing and administration errors [59]. Hence, good nursing practice requires detailed record-keeping that is comprehensive, timely, and accurate. Because, without complete recording, there is no evidence to prove that medical care was offered to the patient [124, 125].

This is supported by the saying in nursing practice that ‘what is not recorded has not been done” [51]. Medication errors are common in general practice and hospitals. Both errors in the act of writing (prescription errors) and prescribing faults due to erroneous medical decisions can result in harm to patients. Any step in the prescribing process can generate errors. Slips, lapses, or mistakes are sources of errors, as in unintended omissions in the transcription of drugs. Faults in dose selection, omitted transcription, and poor handwriting are common. Inadequate knowledge or competence and incomplete information about clinical characteristics and previous treatment of individual patients can result in prescribing faults, including the use of potentially inappropriate medications. An unsafe working environment, complex or undefined procedures, and inadequate communication among healthcare personnel, particularly between doctors and nurses, have been identified as important underlying factors contributing to prescription errors and prescribing faults. Active interventions aimed at reducing prescription errors and prescribing faults are strongly recommended. These should be focused on the education and training of prescribers and the use of online support. The complexity of the prescribing procedure should be reduced by introducing automated systems or uniform prescribing charts to avoid transcription and omission errors. Feedback control systems and immediate review of prescriptions, which can be performed with the assistance of a hospital pharmacist, are also helpful. Audits should be performed periodically [51]. The inappropriate keeping of medical records can influence patient management and the endurance of medical care, leading to inadequate health care [126]. Therefore, the appropriate use of ARVs requires the nurses’ understanding of good medical record-keeping and the importance of it in ART management. Patients’ clinical records, clinic records, and administrative records are the necessary nursing practice records. Medical records explain all relevant patient details such as the history, clinical findings, diagnostic test results, pre and postoperative care, patient’s progress, and pharmacological treatment. If written correctly, notes acquired in these records support a healthcare professional’s correctness of treatment [127]. The appropriate keeping of records is important in nursing care in that it provides clear evidence of the care plan, the decisions made, the care delivered, and the information shared with the patient. It is a means of communication with multidisciplinary health team members [124, 125, 126, 127].

12. Treatment support systems for the children on ART

The nurses in rural clinics need to facilitate local support systems for the parents and caregivers of children receiving ART, as well as identify local community support groups to support, help, and motivate the parents and caregivers of children receiving ART. Nurses need to remember that children depend solely on caregivers for adherence, treatment administration, and presenting to the clinic for a collection of their antiretroviral treatment. Additionally, caregivers can be their primary parents, guardians, older siblings, aunts, uncles, or grandmothers. As clinicians, you can support the parents/caregivers as they suffer emotional strain in caring for children on ART. Give information about support groups in the community of your facility. The emotional well-being of a parent/caregiver plays a huge role towards the child’s adherence to treatment [128, 129, 130].

13. Knowledge of the rational and irrational medicine use concept

Promoting the rational use of ARVs will require effective policies and efficient collaboration between health professionals, patients, and the entire communities. An adequate understanding of the relevant aspects of ARV use among all stakeholders is essential to drive collaborative efforts to address irrational ARV use. The tackling of irrational ARV use should be prioritised to improve healthcare delivery towards ensuring patient safety and allowing for optimal utilisation of the ARVs. Irrational prescribing often derives from a wrong medical decision because of a lack of knowledge or inadequate training. Adverse clinical outcomes can be related to a lack of knowledge or skill. Even the simple act of transcribing previous medications and collecting information as part of the medication history requires knowledge of pharmacotherapy and adequate information about the patient’s clinical condition. Equally, the choice of dose requires information about the patient’s clinical status and immediate verification of the appropriateness of treatment. The provision of continuous in-service training and mentorship on the rational use of ARVs is pivotal for nurses in PHC settings. In addition, the hospital’s Drug and Therapeutics Committee should regularly evaluate ARV usage patterns in these clinics [7].

14. Lessons learned from South African primary healthcare ART programmes

In South Africa, initiating ART in primary care is the responsibility of NIMART-trained professional nurses. It is no doubt that the availability of NIMART-trained nurses in PHC clinics has tremendously improved patients’ access to HIV services [18, 72, 131]. Task-shifting has brought paediatric ART initiation and management into the practice of NIMART-trained nurses. Therefore, the nurses must be equipped with the knowledge and skills vital for this role. The country also introduced the clinical mentoring manual for integrated services through the Department of Health [132], targeted mentorship introduced for nurses in primary health care, and it was found to enhance clinical expertise. Doctors or nurses can become clinical mentors if they undergo mentoring training. In addition, supervisory and mentoring support is viewed necessary to help improve nurses’ confidence in managing paediatric ART patients. Literature, however, reveals that the sustained success of this approach is dependent on factors such as adequate training and effective support systems [131]. Lessons learned from SA also revealed that training, mentorship, and clinical practice experience are associated with knowledge and confidence of NIMART-trained nurses regarding the provision of ART services to children. These studies therefore recommended “the strengthening of the current training and mentoring and ensuring that NIMART-trained nurses are provided with regular updates and sufficient opportunities for clinical practice” [71, 72, 131, 133, 134, 135].

15. Conclusions

The irrational use of medicines occurs at all levels of health care. This practice is also observed in hospital settings, and it contributes to a decrease in the patient’s quality of treatment and often causes negative health consequences. For this reason, it is essential to consider the adoption of appropriate training, mentorship, and support methods as a strategy for promoting the rational use of ARVs. These can be introduced in rural PHC settings to increase the safety and effectiveness of antiretroviral use. This approach has been witnessed in practice to lead to increased quality of life, improved patient care and confidence, and professional development because appropriately trained nurses have been observed to experience work satisfaction due to the difference they make in patients’ lives.

Quality improvement strategies such as mentorship, clinic medical record audits, and automated prescribing systems where possible can be used to address knowledge gaps in practice.

Acknowledgments

This project received funding from the University of Limpopo’s Staff Capacity Development Programme (UCDP), as well as funding from the National Research Foundation Black Academics Advancement Programme (BAAP) (previously known as) National Research Foundation (NRF) - First Rand Foundation (FRF) Sabbatical Grant (Ref No: NFSG180605340566, Grant No: 116803).

Conflict of interest

The authors in this study declare that there is no conflict of interest, financial or otherwise.

Notes/thanks/other declarations

None.