UNIVERSITY OF MALAWI. College of Medicine

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UNIVERSITY OF MALAWI College of Medicine Factors Affecting Adherence To Antiretroviral Therapy (ART) Among Children Aged 7-15 Years Attending Queen Elizabeth Central Hospital (QECH) ART Clinic In Blantyre

By Lucy Guluka Gawa BSC in Nursing Education and Administration, Diploma in Nursing (MPH/007/008)

Dissertation Submitted in Partial Fulfillment of the Requirements of the Master of Public Health Degree

June 2011

CERTIFICATE OF APPROVAL

The Thesis of Lucy Guluka is approved by the Thesis Examination Committee

_________________________________________________ (Chairman, Postgraduate Committee)

__________________________________________________ (Supervisor)

____________________________________________________ (Internal Examiner)

_____________________________________________________ (Head of Department)

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DECLARATION

I, Lucy Guluka hereby declare that this thesis is my original work and has not been presented for any other awards at the University of Malawi or any other University.

Name of Candidate:

Lucy Guluka

Signature:

Date:

27th June 2011

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ACKNOWLEDGEMENTS I wish to express my special thanks to the department of Community Health at College of Medicine for awarding me a scholarship to study MPH at their institution. Secondly, my heartfelt gratitude is due to Professor Cameroon Bowie, Dr Peter Moons for continuously guiding me through the development of research proposal and Professor Victor Mwapasa for valuable contributions, guidance and support throughout the production of this thesis. I am very grateful to my family for being there to encourage and support me during the period of study. I thank Nurse Madalitso Daza for assisting me with data collection, and not forgetting Egnat Katengeza and Emmanuel Singogo for your assistance during data analysis. Your input contributed to the success of this project. I also appreciate the management at Queen Elizabeth Central Hospital for allowing me conduct this research in their institution Above all, I am very grateful to God, the Almighty for keeping me in good health to enable me carryout this research project, to Him be the Glory and Honor for ever and ever.

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ABSTRACT BACKGROUND: The introduction of antiretroviral therapy (ART) has given hope to many people living with HIV/AIDS including children. ART is effective in suppressing HIV replication, decreasing morbidity, and mortality and improving quality of life, therefore adherence to this medication is very crucial [1]. Sustaining adherence represents a significant challenge for children getting treatment at Queen Elizabeth Central Hospital (QECH). STUDY OBJECTIVE: The purpose of this study was to investigate the factors that affect adherence to ART among children attending QECH ART clinic in Blantyre. STUDY METHODS: This was a cross-sectional descriptive study combining quantitative and qualitative methods. An interviewer administered questionnaire was used to collect data in children. Focus group discussions (FGDs) were conducted with caregivers. A systematic sample of HIV-infected children was drawn on daily basis. Quantitative data was analyzed using StataSE 10 whilst qualitative data was coded using Non-Numerical Unstructured Data Indexing, Searching and Theorizing (NVIVO) software (QSR, 2001). Adherence was ascertained by asking patients whether they missed any medication from the previous visit to the current visit, therefore in this study adherence is defined as not missing any dose from the previous visit to the current visit (which is usually two months), according to self reports. RESULTS: Ninety eight children were enrolled in the study, of which 62.3% (61/98) were 100% adherent. Among children who missed doses, the common reason for missing doses was forgetfulness. Adherence to ART was significantly associated with perceived health status (P=0.03, OR=2.1, 95% CI: 1.1-4.1) while guardian of child having an occupation or not was marginally associated (P=0.1, OR=2.3, 95% CI: 0.9-5.8). The most common strategy used in ensuring an effective ART adherence was a reminder to take the drug by caregivers to their children to take the pill. CONCLUSION: The results for this study showed that over one third of the children in this clinic are not 100% adhering to ART. An adherence programme that will adequately prepare patients and guardians prior to initiating treatment and provision of an ongoing ART adherence support should be developed in the ART clinic.

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TABLE OF CONTENTS Certificate of approval ......................................................................................................................... i Declaration ........................................................................................................................................... ii Acknowledgements ............................................................................................................................ iii Abstract ................................................................................................................................................ iv Table of Contents ................................................................................................................................ v List of Abbreviation............................................................................................................................. x List of Tables .................................................................................................................. ix CHAPTER 1: Background to Study ................................................................................................. 1 1.1 HIV/AIDS Situation in the World ......................................................................................... 1 1.2 HIV/AIDS and ART in Malawi.............................................................................................. 1 1.3 Statement of the Problem ........................................................................................................ 2 1.4 Literature Review ....................................................................................................................... 2 1.4.1Definition of Adherence .................................................................................................... 2 1.4.2 Importance of Adherence ................................................................................................. 3 1.4.3 Measurement of Adherence ............................................................................................. 3 1.4.4 Adherence Levels In Africa and Malawi ......................................................................... 4 1.4.5 Factors Affecting Adherence .......................................................................................... 5 1.5 Justification of the Study .......................................................................................................... 7 CHAPTER 2: Study Objectives ......................................................................................................... 8 2.1 Broad Objective ......................................................................................................................... 8 2.2 Specific Objectives .................................................................................................................... 8 CHAPTER 3: Methodology ............................................................................................................... 9 3.1 Study Design .............................................................................................................................. 9 3.2 Study Setting .............................................................................................................................. 9 3.3 Study Population........................................................................................................................ 9 3.4 Study Period ............................................................................................................................... 9 3.5 Sample Size ................................................................................................................................. 9 3.6 Data Collection ........................................................................................................................ 11 3.7 Data Management and Analysis ............................................................................................ 11

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3.8 Definitions of Terms............................................................................................................... 12 3.9 Ethical Consideration.............................................................................................................. 13 CHAPTER 4: Study Results ............................................................................................................. 14 4.1 Characteristics of Participants................................................................................................ 14 4.2 Knowledge of Treatment Type and Reason for Treatment ............................................. 15 4.3 Medication Adherence ............................................................................................................ 17 4.4Factors associated with ART .................................................................................................. 18 4.5 Belief in efficacy of Medication ............................................................................................. 21 4.6 Disclosure of Status................................................................................................................. 22 4.7 Adherence Strategies ............................................................................................................... 23 4.8 Medication Support ................................................................................................................. 24 4.9 Medication Instructions .......................................................................................................... 25 5.0 Communication Problems ..................................................................................................... 26 CHAPTER 5: Discussion ................................................................................................................. 27 5.1 Study Limitations ..................................................................................................................... 32 CHAPTER 6: .................................................................................................................................... 34 6.1 Conclusion ................................................................................................................................ 34 6.2 Recommendations .................................................................................................................. 34 6.3 Further Research...................................................................................................................... 35 REFERENCES ................................................................................................................................. 36 APPENDICES................................................................................................................................... 42 Appendix 1: English Version Informed Consent ......................................................................... 42 Appendix 2: Chichewa Version Informed Consent ...................................................................... 43 Appendix 3 : English Version Study Questionnaire ..................................................................... 48 Appendix 4: Chichewa Version Study Questionnaire .................................................................. 48 Appendix 5: English Version Focus Group Guide ...................................................................... 52 Appendix 6: Chichewa Version Focus Group Guide ................................................................... 54 Appendix 7: Approval Letter by Hospital Director (QECH) ..................................................... 57

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List of Tables Table 1: Characteristics of Participants ........................................................................................... 14 Table 2: Treatment Type and/or Name ......................................................................................... 16 Table 3: Reasons for Missed Doses................................................................................................. 17 Table 4: Factors Associated with ART Adherence (Univariate analysis)................................... 18 Table 5: Factors Associated with ART Adherence (Multivariate analysis) ................................ 21 Table 6: Reasons Why Medication is Helpful ................................................................................ 21 Table 7: Reasons for Disclosure and Non-Disclosure of HIV Status ....................................... 22 Table 8: Adherence Strategies .......................................................................................................... 23 Table 9: Kind of Medication Support ............................................................................................. 24 Table 10: Medication Instructions ................................................................................................... 25

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List of Figures Figure1: Association between Education Level and Adherence ................................................. 20

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List of Acronyms AIDS

Acquired Immune Deficiency Syndrome

ART

Antiretroviral Therapy

ARV

Antiretroviral

COM

College of Medicine

COMREC

College of Medicine Research and Ethics Committee

FGD

Focus Group Discussion

HAART

Highly Active Antiretroviral Therapy

HCW

Health Care Worker

HIV

Human Immune Deficiency Virus

MTCT

Mother to Child Transmission of HIV

MOH

Ministry of Health

MPH

Masters of Public Health

QECH

Queen Elizabeth Central Hospital

WHO

World Health Organization

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CHAPTER 1: BACKGROUND 1.1 HIV/AIDS in Sub-Saharan Africa HIV/AIDS is one of the public health challenges in the world. In 2009, it was estimated that over 33.3 million people were living with HIV/AIDS worldwide, with 2.5 million of these being children under 15 years of age. The epidemic is worse in developing countries, particularly in Sub-Saharan Africa, with 22.5 million people living with HIV/AIDS by the end of 2009[2]. Unprotected heterosexual contact is by far the primary mode of transmission of HIV virus in adults while Mother to Child Transmission (MTCT) is the largest source of infection in children below the age of 15 years. Without treatment, 15-30% of babies born to HIV positive women become infected with HIV during pregnancy and delivery. Furthermore, an additional 5-20% becomes infected through breastfeeding [3]. The introduction of antiretroviral therapy (ART) has given hope to many people living with HIV/AIDS, including children. ART is effective in suppressing the replication of HIV, decreasing morbidity and mortality associated with HIV and improving quality of life in adults as well as children [1]. 1.2 HIV/AIDS and ART in Malawi While Sub-Saharan Africa is highly rated on HIV/AIDS prevalence, Malawi through a recent survey conducted in 2007, contributed about 900 000 people living with HIV/AIDS to the Sub-Saharan African figure., with about 89 000, of these being children under 15 years of age [4]. Like other countries in Sub-Saharan Africa, the primary mode of HIV transmission in Malawi is unprotected heterosexual sex, while mother-to-child transmission is the second major mode of HIV transmission. In response to the WHO “three by five” initiative which aimed to have three million people in developing countries on ART by the end of 2005, Malawi developed a two-year (20042005) antiretroviral expansion plan with the goal of delivering free ART to 80 000 eligible patients throughout the country by the end of 2005[5]. By December 2005, 37 840 Malawians were ever started on ART 4]. At the end of March 2006 the HIV Unit of the Ministry of Health (MOH) reported 2,718 children (younger than 15 years old) on ART, with the majority of the children (70%) from the southern region, 26.6% from the central

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region and 3.4% from the north[6][7]. Malawi aimed to have started 245,000 patients on ART by the end of 2010[3]. As of 2010, a fixed-dose combination of Stavudine, Lamivudine and Nevirapine (Triomune) was the first-line and standard ART regimen for both adults and children in Malawi [4]. Alternative first line are available for all the patients who develop side effects both for adults and children in all facilities while second line ART are available for patients who have developed treatment failure on first line regimen and are found in referral hospitals and selected district hospital where there is specialized care. 1.3 Statement of the Problem For ART to work effectively, adherence is very crucial. The recommended optimal adherence level for ART to be effective is above 95 percent [8]. Any patient who misses more than 3 dosages in a one month treatment course is considered to have achieved suboptimal adherence which is less than 95% [9]. A level of adherence which is greater than 95% (optimal adherence) suppresses viral replication and prevents the development of resistance and treatment failure. Sustaining adherence presents a significant challenge for children receiving ART treatment at QECH pediatric clinic in Malawi. A preliminary assessment using self report of children aged 7-15 years who were attending the QECH clinic and were prescribed ARVs for a period of two months found that only 56% of children were 100% adherent. The assessment attempted to verify self report with pill count but it was observed that pill count was not very accurate because the nurses were sometimes administering more or less tablets than expected. The assessment also revealed that some children did not adhere because they did not know why they were taking ARV drugs. These findings lend support to the recommendations made by Muula in his study “Assessment of equity in the uptake of Anti-retroviral in Malawi” to further assess factors affecting adherence since different adherence rates in different areas were revealed from his study in Malawi] [10].

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1.4 Literature Review 1.4.1 Definition of adherence Adherence is defined as “the extent to which a person’s behavior - taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider”[11]. Adherence to medication is also known as compliance with medication. The term adherence has become preferred to the term compliance because compliance implies the patient is passively following orders, while adherence implies a treatment plan agreed by both patient and physician.[12]. In the case of pediatric patients this can be applied to both the caregiver’s and the child’s behavior hence agreement on treatment recommendations is required from both of them 1.42 Importance of Adherence to ART Medication adherence is fundamental to successful antiretroviral therapy. Adherence is a major factor in determining the degree of viral suppression achieved in response to antiretroviral therapy[13].The goals of ARV therapy for children are to increase survival, improve quality of life and decrease HIV-related morbidity and mortality[14]. Some scholars have argued that adherence greater than 95% will ensure a good virologic response and prevent the emergence of viral resistance, therefore impeding the success of the ART program [1] [6] [14]. Thus, there is evidence that failure to adhere to the prescribed treatment regimen is associated with adverse clinical outcomes. Therefore, efforts to improve adherence rates are likely to result in improved health outcomes. 1.4.3 Measurements of Adherence There are numerous methods that are applied to assess ART adherence. Among the most common are face-to-face interviews or self report and pill count. In face-to-face interviews, the patient is asked about the number of doses missed during a specific period and it is translated quantitatively into a percentage adherence. However, this method has its limitations because patients tend to overestimate adherence [15]. In a study by Liu, adherence as measured by patient interview was found to be considerably higher than adherence as measured by other means, for example pill count [16]. However, self-report is most useful for those patients who admit to poor adherence because such patients truly are non-adherent [15]

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Pill count is done at the clinic, after the patient has brought the pill bottle with him. A healthcare provider counts the number of pills remaining in the bottle and computes the number of missed doses by comparing the difference between the actual and expected number of pills remaining in the bottle. Drawbacks of pill counts include pill dumping, whereby patients dispose off pills to make their adherence appear better than it may actually be [16]. 1.4.4 Adherence levels in Africa and Malawi Different adherence rates have been reported in various studies in both Africa and Malawi. The rates of adherence varied with study characteristics and method of ascertainment of adherence i.e. individual reports, pharmacy records and pill counting [13] [17]. Some studies have reported that fewer than 50% of children and/or caretakers report 100% adherence to their clinically prescribed regimens [13]. However, others have reported adherence interms of mean adherence rates of greater than 90% [18]. A systematic review and meta-analysis of studies in adults evaluating adherence to ART in sub-Saharan Africa and North America

reported a combined continent estimate of adherence rates of 64%. The

pooled estimate for the North American studies was 55% and for the African studies was 77%, indicating a higher level of ART adherence in Africa [19]. However this review did not state the proportions of people associated with the reported adherence rates. In Malawi, two studies conducted by Medicines San Frontiers (MSF) to assess levels of adherence in Chiradzulu and Thyolo districts also revealed varied levels of adherence. In Chiradzulu they measured the pill count for 367 patients of which (64%) of patients were highly adherent (implying they took medication in the previous four days 100% of their time), 27% were moderately adherent (implying they took medication at least 80% and less than 100% of their time) and 9% were non-adherent (meaning they took medication less than 80% of their time). Using patient self-reporting, 383 (96%) were found to be highly adherent, 8 (2%) were moderately adherent and 16 (4%) were non-adherent. In Thyolo district, out of 151 patients, 99% had at least 95% adherence, using pill count [10]. Another study conducted in Blantyre at QECH ART clinic (before the clinic started providing free ART) assessed 176 patients and found that 52% reported to have 100% adherence never

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having missed a dose. Of those that missed a dose, 43% reported that they had missed medications because of unavailability of medications at the hospital pharmacy, 32% because of lack of money and 27% had forgotten to take medications [20]. Another study conducted by Bell in adult patients, at the same hospital showed complexities of measuring adherence and probable overestimation of adherence by pill count (98.6%) and self report (86.2%) compared to medication event monitoring system (88.1)[21]. In 2004 to 2005, Ellis and Molyneux in their study “ Experience of Anti-retroviral treatment for HIV infected children in Malawi found that adherence using self report was excellent, better than 95% in >90% of the children[22]. However, this was the only study that looked at adherence in children. 1.4.5 Factors affecting Adherence Studies conducted in developed countries have revealed various factors affecting ART adherence in children. There are very few studies conducted in Africa and none have been published from Malawi. However, from all these studies, the following factors are revealed. 1.4.5.1 Drug Formulation and Complexity When treating HIV infected pediatric patients, fewer options are available, because of the small number of ARV drugs registered worldwide for pediatric use and/or inadequate formulations [23]. This significantly limits the possibility of prescribing drugs that are easy to administer to children. In addition, regimen complexity is another important contributor to poor adherence [24]. This includes the need for daily administration, dietary requirements, dosage and consequently pill burden, and pill taste [13] [25] [26] [27]. However, some studies discovered that adherence was not associated with the complexity or burden of medication regimens despite the fact that most providers often believe this to be a critical barrier to adherence [28]. 1.4.5.2 Side effects Studies have revealed that ARV drugs are often discontinued when side effects occur or when they are perceived. Adverse drug events influence willingness to take medication and are consistently associated with poor adherence [24] [28]. In another study by Heyer, patients with adverse events such as dermatological and gastrointestinal symptoms were 12.8 times

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less likely to be 95-100% adherent [24] compared with those who did not present with symptoms 1.4.5.3 Beliefs and attitude Parents’ beliefs and attitudes are among the predictors of ART adherence. Parents’ beliefs about the seriousness of their childs’

illness and the medication or treatment, will

influence adherence[29]. In addition, the child’s attitude towards the drug, his perceptions about the HIV the perceived benefits of the drug play a very important role in adherence. Greater adherence is observed in patients who believe HAART is effective, while negative beliefs reduced adherence [30]. 1.4.5.4Clinical status The current experiences with symptoms and severity of such symptoms in HIV patients are associated with adherence. Studies have revealed that patients who have symptomatic disease or who feel debilitating pain and symptoms are less adherent [28] compared with patients who did not present with any symptom and pain. However, in one study an increasing adherence rate was observed in children with more advanced AIDS [31]. 1.4.5.5 Age Age has been identified as a relevant factor to consider when looking at adherence to HAART among HIV patients. Some studies have reported better adherence among older patients whilst others have reported no relationship [28] [30]. However, since children are dependent on their caregivers for the administration of medication, adherence is thus only as good as the caregivers are able to achieve. Other studies have revealed that special issues relating to adherence exist for HIV-infected children and adolescents. It is observed that adherence concerns intensify as children enter into adolescence because of premature responsibility for taking medication, and the developmental and social challenges faced [27]. 1.4.5.6 Disclosure of HIV status Disclosure of HIV status is another factor which is believed to have an influence on ART adherence. Some studies have revealed that complete parental disclosure to children helps to motivate HIV-infected children to adhere to their daily medical regimen. It enables children

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to understand HIV infection and to make sense of disease-related experiences and the importance of adherence [32]. However, many caregivers decide not to tell their children that they have HIV disease until adolescence, potentially impeding their cooperation with treatment [27]. 1.4.5.7 Costs Studies conducted in Africa revealed that the cost of drugs and related health service are the most significant barriers to adherence. Adherence difficulties related to the financial demands of therapy and inability to afford medicines for varying periods were reported in Botswana and Uganda by both patients receiving subsidized and non subsidized ART[33][34]. 1.4.5.8 Provider support A supportive patient-provider relationship is another important factor in improving ART adherence. Studies have reported a positive relationship between provider support and adherence. This involves supporting the patient throughout his treatment, by providing motivation, routine adherence counseling, involving the patient in treatment decisions, open communication, compassion and taking regimen inconveniences into account to improve adherence [29]. 1.5 Justification for the Study In order to facilitate adherence to ART in HIV-infected children, it is necessary to know factors that affect adherence and to explore the possible interventions to improve adherence. In view of this, it was vital that a study be conducted to assess levels of adherence among children on ART and factors associated with adherence at QECH ART clinic. This study would help inform the hospital, MoH and other policy makers in Malawi on ways of improving and/or maintaining adherence to ART in children as access to ARV medicines is being scaled up nationwide.

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CHAPTER 2: STUDY OBJECTIVES The study was designed to achieve the following objectives: 2.1 Broad Objective To explore the factors associated with ART adherence in HIV infected children aged between 7 and 15 years attending QECH ART Clinic. 2.2 Specific Objective a. To estimate the proportion of patients who have adherence 100% to ART over a period of two months b. To ascertain the children’s knowledge of their HIV diagnosis and treatment c. To correlate the relationship between diagnostic disclosure and ART adherence. d. To identify the main factors that affect ART adherence including caregivers/children perceptions, beliefs and practices e. To establish the kind of support currently given to infected children under ART

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CHAPTER 3: METHODOLOGY 3.1 Study Design This study used a cross-sectional descriptive study design using both quantitative and qualitative methods. 3.2 Study Setting The study took place at Queen Elizabeth Central Hospital (QECH) which is the largest central hospital in the southern region of Malawi. QECH serves as both a primary contact hospital and a regional referral hospital. The hospital started providing free ART services to HIV infected people in accordance with the national ART guidelines in 2004. Currently, the ART clinic provides HIV related services for both adults and children. The pediatric clinic opens twice a week (Mondays and Tuesdays afternoon) whilst the adult clinic opens daily. 3.3 Study Population The study target population was children aged between 7- 15 years that were attending QECH ARV Clinic in Blantyre, Malawi. The inclusion criteria for the study were: o Known HIV Positive children o Age between 7 to 15 years old (This age category was chosen because of their capacity to reasonably express their views hence able to participate in this study) o On ART Treatment for not less than 2 months excluding initiation period o Guardian may be biological parent, relative or adoptive caregiver o Willing to provide Consent 3.4 Study Period The study was conducted between March and May 2010. The activities that took place during this period include, briefing of research assistant, data collection and data analysis. 3.5 Sample size At the time of the study, the pediatric ART clinic at QECH had 360 patients in the age range of 7 to 15 years registered for ART. To calculate sample size we estimated that only 56% of the patients were adhering 100%, based on a preliminary adherence assessment conducted in

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the clinic. Using this as a point estimate and allowing for a 10% margin of error with 95% confidence, we calculated the sample size to be 98. Since it was difficult for the clinic to come up with a list of HIV infected children expected to come in a particular day from the clinic registry, the researchers attempted to select participants each clinic day through systematic sampling of every second child coming to the clinic. However, due to the clinic set up, patient flow and the turn up of children at their own time, it was difficult to adhere to the sampling method; as a result children who were meeting the criteria were purposively selected and interviewed as they reported to the clinic 3.6 Data Collection Each clinic day during data collection, the researchers with the help from the clinic staff (who were registering and weighing the children) were identifying the potential eligible clients who have reported for the clinic, before they were reviewed by the clinicians. Each child and her guardian were referred to the researchers to be informed about the study and were asked to give an oral consent upon understanding of the specifics of the study. A direct face-to-face interviewer administered questionnaire was used to collect data. The questionnaire had structured and semi structured questions to collect both quantitative and qualitative data. The interview included items on social demographic data, perceived functional health status using a Lansky Performance Scale for children. This scale comprises of indices for the clinical estimate of a person’s physical state, performance and prognosis after therapy and for determining patient’s suitability for therapy [35]. Other information that was collected during the interviews include;

Childs awareness of HIV status,

perceptions towards the prescribed ART, missed doses since the previous visit and in the past week, the kind of support a child receives from her/his guardian and what they do to ensure ART adherence. Upon completion of the individual interviews, data was also collected through focus group discussions (FGD) of guardians to triangulate the information obtained from face-to-face interviews. Each clinic day during registration, guardians meeting the inclusion criteria were informed of the FGD and asked to come to the playroom before weighing and reviewing

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their children. When a minimum of 6 guardians was achieved, the FGD was initiated. A total of four FGD (with between 6 and 8 guardians in each group) were done. The discussions were tape recorded to capture all information provided by the participants. Health passport books were reviewed to confirm the patient report on treatment type, dosage and last date of visit. Other clinic records were reviewed to abstract the number of pills given in the last visit for each child to help calculating the number of missed doses during analysis. A nurse from another department was trained to assist in data collection hence the researcher and the trained nurse interviewed a minimum of 12 children each day until the sample size was met. 3.7 Data Management and Analysis The study completed questionnaires and signed consent forms were collected on daily basis. The researcher checked for completeness and accuracy of the forms and put them in order of numbers to be entered into a data base that was created in Microsoft Access. Quantitative data was later imported into STATA for analysis. Descriptive statistics were computed. We examined any association between various variables and ART Adherence amongst participants using a two-sided chi-square test.

We first conducted univariate

analysis and variables with a p-value
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