DETERMINANTS OF TREATMENT ADHERENCE AMONG TUBERCULOSIS-INFECTED HIV PATIENTS IN CROSS RIVER STATE, NIGERIA

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DETERMINANTS OF TREATMENT ADHERENCE AMONG TUBERCULOSIS-INFECTED HIV PATIENTS IN CROSS RIVER

STATE, NIGERIA

BONIFACE AYANBEKONGSHIE USHIE MATRICULATION NUMBER: 136764

B.SC – SOCIOLOGY (CALABAR) M.SC – SOCIOLOGY (IBADAN)

[email protected]

A THESIS SUBMITTED TO THE DEPARTMENT OF SOCIOLOGY, FACULTY OF THE SOCIAL SCIENCES,

UNIVERSITY OF IBADAN, NIGERIA, IN PARTIAL

FULFILMENT OF THE REQUIREMENT FOR THE AWARD OF

DOCTOR OF PHILOSOPHY IN SOCIOLOGY

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ABSTRACT

Concurrent tuberculosis and HIV treatment is a standard practice in co-infected patients.

However, adherence to combined treatment is challenging because of multiplicity of drugs involved. Although studies exist on adherence to either HIV or tuberculosis treatment, negligible attention has been paid to adherence among patients on combined HIV and tuberculosis treatments. This study therefore examined the factors influencing treatment adherence among tuberculosis-infected HIV patients in Cross River State (CRS), where prevalence is higher than the national average.

Parsonian Social Action theory, Social Cognitive theory and Health Belief Model were employed as theoretical framework. The study adopted a cross-sectional design using 333 patients. A three- stage purposive sampling technique was used to select respondents. This involved identification of treatment facilities across CRS, selection of facilities that had up to 10 co-infected patients and selection of patients who had received concurrent treatment for three months or more prior to the study. A semi-structured questionnaire was used to generate data. Adherence was assessed with a 14-item scale categorised as low (>7), moderate (2-7) and high (0-1). Knowledge was measured using a 17-item instrument categorised as low (≤8) and high (>8). Four Focus Group Discussion sessions comprising seven discussants each were conducted and four case studies were undertaken with patients. Quantitative data were analysed using descriptive statistics, Chi-square and ordinal regression test at 0.05 level of significance while qualitative data were content analysed.

The mean age of respondents was 34.5±9.6 and 61.9% were female. Fifty-seven percent of respondents had high knowledge of treatment and 48.7% did not link poor adherence to poor treatment outcomes. Level of adherence was high (38.1%), moderate (29.4%) and low (32.4%). Adherence to tuberculosis treatment was significantly higher than to HIV treatment.

Respondents‘ reasons for missing drugs included not being at home (64.7%), not having eaten (45.5%), being busy (44.9%) and avoiding status disclosure (25.1%). Having good knowledge of treatment was significantly related to low level of adherence. The likelihood of adherence was significantly high among males (OR: 1.8; 95% CI: 0.4-2.4), those with a minimum of secondary education (OR: 2.7; 95% CI: 1.2-3.4) and those not living in the same community as the location of their treatment facility (OR: 1.7; 95% CI: 1.0-3.5). Patients who received adequate social support showed the likelihood of better adherence relative to those who received little or no support (OR: 3.0; 95% CI: 1.3-4.7). Patients reported that when in the

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3 midst of other people, they did not want to be seen using drugs to forestall stigmatisation.

Respondents demonstrated enthusiasm at the start of the treatment but adherence reduced when difficulties were encountered. Respondents whose spouses or regular sexual partners were not infected encountered more difficulties with adherence because they were believed to be under spiritual attacks not HIV. Patients benefitted much from counselling and good care- provider/patient relationship.

Treatment adherence among tuberculosis-infected HIV patients was influenced by personal characteristics and health facility location. Training on how to overcome the stigma, initiation of patient-selected treatment facility options and policies that emphasise sustained patient counselling could improve adherence.

Key words: Treatment adherence, Co-infected patients, HIV, Tuberculosis, Patient counselling Word count: 500

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ACKNOWLEDGEMENTS

I wish to first and foremost appreciate two persons without whom I would not have enrolled for a PhD. The first of these two is Professor Ayodele Samuel Jegede. I had no intention whatsoever of pursuing a PhD until Prof Jegede, who had supervised my MSc research, insisted that I must.

When I complained that I did not have the financial wherewithal to pursue a PhD degree, but he promised that he was either pay for it or teach me how to get a scholarship to pay for the programme. When I finally agreed to start the doctoral degree, I knew I was bidding time for a job to come along. However, as I started working on it, my interest in the programme increased.

I have nothing to do but to give all the thanks to my supervisor, Prof Jegede, for starting me on the programme, and for guiding me through it all even when I felt so tired and wanted to give it up.

The second person, Professor Isiugo-Abanihe, had so much belief in me that I could not believe it myself. It was he who had called me back to continue my MSc programme which I had abandoned for a month because of financial difficulties. He continued to take interest in my progress, and challenged me at all times to improve myself. My heartfelt gratitude goes to Prof Isiugo-Abanihe. In addition, I am grateful to the Department of Sociology and its entire staff thereof, for providing the enabling environment for me to pursue my studies successfully.

Professors Oka Obono and Olanrewaju Olutayo, Drs Ezebunwa Nwokocha, Emeka Okafor and Raheed Okunola are especially appreciated. Also, with gratitudefrom deep places, I remember the departmental secretary, Mrs Idowu.

To my family, the expression ―thank you so much‖ will never be enough for all you have been through for me. However, for want of anything more suitable, I have to say thank you, especially to my parents: Mr Andeshi Ushie and Mrs Theresa Andeshi Ushie; without you, I could not have accomplished anything. My siblings are also greatly appreciated for all their love and kindness. A special thank you to my uncle, Mr Upel Ushie (hoping for you to defend your PhD soon, so we can change this title) for encouraging and supporting me.

I owe many friends my gratitude. I shall only mention a few, even if your name is not found here, know it for a certainty that all my friends are appreciated. Dr David Ugal has been with me from the beginning of every intellectual journey I have ever undertaken, and has been a strong pillar of support for me. Others include Eunice Udida (I hope she understands), Romanus Aboh, Dr Gilbert Adie, Justin Ingwu, Magnus Lakim Lekan, Mr Raymond Obaji, Ogadimma

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5 Arisuchu, Nnanna Emmanuel Patrick and Mrs Undie. I reserve very special praise for Dr Rachel Anita Weber for the many things she taught me at the beginning of the PhD and her friendship.

Christopher Michael Eraye, a good friend who also supervised my data collection, must be greatly appreciated, as well as all those who worked tirelessly to collect the data.

My sincere appreciation to the Obudu community in Ibadan, who make living here as much as possible close to being at home. I will only mention a few: Mr. Mike Oko, Ukandi Amunde, Christopher Abugbe and Capt Mike Agim.

I reserve the best for last (so I can savour the taste for a long time). This unqualified appreciation goes to my precious ―baby-wifey‖, Charity Ushie. Indeed, just writing your name brings so much happiness to my mind, and reminds me of beautiful poetry written by the fireside in the chilling harmathan of the hilly region of Obudu, Cross River State. May God keep my baby- wifey safe and sound!

Whether your name appears here or not, you are appreciated, if you deserved to be appreciated.

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FINANCIAL SUPPORT

My most sincere appreciations go to the Dan David Prize Scholarship, Council for the Development of Social Science Research in Africa (CODESRIA) and African Doctoral Dissertation Research Fellowship (ADDRF) hosted by the African Population and Health Research Centre in Nairobi, Kenya, sponsored by the International Development Research Centre (IDRC), Canada and Ford Foundation, which provided financial assistance. In no small measure, these grants changed the progress not only of this work but also of my life generally.

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CERTIFICATION

This is to certify that this research is an original work carried out in the Department of Sociology, Faculty of the Social Sciences by Boniface Ayanbekongshie USHIE under my supervision.

………

SUPERVISOR Professor Ayodele S. Jegede

B.Sc (Hons), M.Sc (Ife), PhD (Ibadan), MHSc (Toronto) Department of Sociology

University of Ibadan, Ibadan, Nigeria.

DEDICATION

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8 This work is dedicated to the Almighty God who provided me with the ability, courage and inspiration to carry on in spite of difficulties.

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10 2.1.9 Gender, HIV Vulnerability and Treatment Adherence 32

2.1.10 Stigmatisation and Adherence 36

2.1.11 Interventions to Improve Patient Adherence 36

2.1.12 Summary of Review 40

2.2 Theoretical Framework 40

2.2.1 Social Action Theory 40

2.2.2 Health Belief Model 42

2.2.3 Social Cognitive/Learning Theory 44

2.2.4 Conceptual Framework 46

2.3 Hypotheses 49

CHAPTER THREE METHODOLOGY

3.1 Research Design 50

3.2 Study Areas 50

3.3 Study Population 51

3.4 Sample Size Determination 51

3.5 Sampling Procedure 53

3.6 Methods and Instruments of Data Collection 53

3.6.1. Semi-structured Questionnaire 53

3.6.2 In-depth interviews 55

3.6.3 Focus Group Discussions 56

3.6.4 Case Histories 56

3.6.5 Health Records 56

3.7 Validity of the Instruments 56

3.9 Reliability 57

3.10 Procedure for Data Collection 57

3.11 Data Management 58

3.12 Analyses of Data 59

3.13 Limitations 59

3.14 Delimitations 60

3.15 Ethical Considerations 60

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11 CHAPTER FOUR

DATA PRESENTATION AND DISCUSSION OF FINDINGS

4.1 Data Presentation 62

4.1.2 Socio-Demographic Characteristics 62

4.1.3 Knowledge of Implication of Treatment Adherence 66

4.1.4 Adherence to Treatment 73

4.1.5 Factors affecting adherence to the treatment 87

4.2 Discussion of Findings 122

CHAPTER FIVE

SUMMARY OF FINDINGS, CONCLUSION AND RECOMMENDATIONS

5.1 Summary of Findings 131

5.2 Conclusion 133

5.3 Recommendations 133

REFERENCES 135

APPENDICES

Appendix I Semi-Structured Questionnaire 157

Appendix II In-Depth Interview Guide for Health Caregivers 167 Appendix III In-Depth Interview Guide for Friends and Family Members 169 Appendix IV Focus Group Discussion Guide for HIV and TB Co-Infected Patients 171

Appendix V Case History 173

Appendix VI Patients‘ Hospital Record Guide 174

Appendix VII Pigin English Questionnaire 175

Appendix VIII Efik Language Questionnaire 185

Appendix IX Lokkurr Language Questionnaire 195

Appendix X Consent Form 207

Appendix XI University of Ibadan/University College Hospital Ethical Approval 209

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LIST OF TABLES

Table 3.1: Estimated number of Tb-infected HIV patients by health care

facility and type of treatment services 52

Table 4.1 Distribution of Respondents by Demographic Characteristics 63 Table 4.2: Distribution of Respondents by Socio-economic Characteristics

According to Sex 65

Table 4.3: Distribution of Respondents by Knowledge of the Consequence of

Non-adherence 67

Table 4.4: Distribution of Respondents by the Consequences of Non-adherence

Identified 69

Table 4.5: Percentage Distribution of Respondents According to Knowledge of

Treatment by Selected Characteristics 72

Table 4.6: Estimated Days Respondents Missed Medication Two Months

Prior to the Study using Hospital Records by Selected Variables 78 Table 4.7: Percentage Distribution of Level of Adherence According to

Socio-Demographic Characteristics 79

Table 4.8: Distribution of Respondents by Level of Adherence according

to selected variables 84

Table 4.9: Level of adherence according to family support received

and level of anxiety 86

Table 4.10: Percentage Distribution of Respondents‘ Perceived

Self-efficacy According Selected Characteristics 88 Table 4.11: Percentage of Respondents According to Means of

Transportation to Treatment Facility by Selected Characteristics 90 Table 4.12: Mean Amount (in Naira) Paid on Transport Fare to and from

Treatment Facility by Selected Characteristics 91

Table 4.13: Distribution of Respondents according to Level of

Anxiety by Selected Characteristics 98

Table 4.14: Level of Anxiety by location, Time on Drugs and Transport Cost 100 Table 4.15: Respondents‘ Feeling of Social Isolation by Location,

Time on Drugs, Transport Cost and Number of Children 102 Table 4.16 Distribution of Respondents‘ Feeling of Social Isolation by

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Selected Characteristics 104

Table 4.17: Distribution of Respondents by Type of Support Received from

Family and Friends 109

Table 4.18: Distribution of Respondents according to Level of

Satisfaction with Support Received by Type 113

Table 4.19: Distribution of Respondents by Level of Support

Received according to Selected Characteristics 114

Table 4.20: Distribution of Respondents Level of Self-stigma

According to Selected Characteristics 117

Table 4.21: Distribution of Respondents Level of Social

Stigma according to Selected Characteristics 119

Table 4.22: Ordinal Regression Modelling the Predictors of

Adherence to Treatment 121

LIST OF FIGURES

Figure 2.1 Conceptual Framework linking Health Belief Model and Social

Cognitive Theory to Explain Adherence 47

Figure 4.1: Distribution of Respondents According to Knowledge of Treatment 71 Figure 4.2: Proportion of Respondents Who Had Ever Missed their Drugs or the

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Actual Time of Taking Drugs 74

Figure 4.3: Respondents‘ Level of Adherence to Treatment 76 Figure 4.4: Level of Treatment Adherence by Time on HIV Treatment 81 Figure 4.5: Level of Treatment Adherence by Time on Tb Treatment 83 Figure 4.6: Proportion of Respondents Who Absented from Work to Attend Clinic

and Who Spent Money to Eat while in the Treatment Facility 93

Figure 4.7: Respondents‘ Reasons for Missing Drugs 95

Figure 4.8: Proportion of Respondents who take any Alcoholic Drink 106 Figure 4.9: Respondets who Live in the Same Household with Family and

Friends and who have Recieved any Support 108

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ABBREVIATIONS USED IN THE TEXT

Abbreviation Full meaning

AACTG Adult AIDS Clinical Trial Group

AGIL Adaptation, Goal attainment, Integration, and Latency

APHA American Public Health Association

ART Anti-Retroviral Therapy

ARVs Anti-Retroviral Drugs

CRS Cross River State

DOT Directly Observed Therapy

FGD Focus Group Discussion

HAART Highly Active Anti-Retroviral Therapy

HBM Health Belief Model

HIV/AIDS Human Immune-Deficiency Virus/Acquired Immune Deficiency Syndrome

IDI In-Depth Interview

IMR Infant Mortality Rate

MMR Maternal Mortality Rate

NACA National Agency for the Control of AIDS

NNRTIs Non-nucleoside Reverse Transcriptase Inhibitors PEPFAR President‘s Emergency Plan for AIDS Relief

PI Protease Inhibitors

TB Tuberculosis

UCH University College Hospital

UCTH University of Calabar teaching Hospital

UNGASS United Nations General Assemble

USAID United States Agency for International Development

WHO World Health Organisation

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CHAPTER ONE INTRODUCTION 1.1 Background to the Study

Human Immunodeficiency Virus (HIV) and Tuberculosis (Tb) co-morbidity constitutes a public health crisis. The co-morbidity between HIV and Tb was first noted in the early 1980s (Bryt and Rogers, 1994), and reports have since shown a much greater than expected incidence of Tb in HIV patients (Dong, Thabethe, Hurtado, Sibaya, Dlwati, Walker and Wilson, 2007; Wood, 2007). Infection with HIV suppresses the immune system, thus, making it easy for other opportunistic infections like Tb to further weaken the HIV-infected person‘s immune system. Tuberculosis is the most frequent co-infection among HIV-infected patients worldwide (Ojikutu, 2007), with much of the incidence of co-morbidity occurring in low- and middle-income countries where limited resources constrain access to medication (Gray and Cohn, 2013). In fact, epidemiologic evidence indicates that HIV epidemic contributes substantially to increase in Tb infections (Shargie and Lindtjorn, 2007; Datiko, Yassin, Chekol, Kabeto, and Lindtjorn, 2008).

The prevalence and incidence of Tb in the general population vary substantially across countries and regions. The escalating HIV and Tb epidemics have had a significant impact on public health services in resource-limited settings. The greatest Tb/HIV co-infection burdens are on the African continent where Tb treatment success has been historically low. Only about 50.6 percent of all co-infected persons are currently on medication in Nigeria [United Nations General Assembly, (UNGASS), 2007], and with the fragility and complex global and local politics of funding, the shortage may become acute in a few more years (Omenka and Zarowsky, 2013). In Nigeria, the rate of Tb-HIV co-infection is said to be 9.5 percent.

Nigeria is reported to have the third highest HIV-infected persons worldwide (UNGASS, 2007) and the fifth highest Tb rates (WHO, 2008). In the African continent, Nigeria‘s number is second only to that of South Africa with respect to HIV infection.

Access to anti-HIV and anti-Tb treatment services is a critical need, especially in resource- poor and difficult-to-reach settings. However, the fight against the co-infections can no longer be limited to the provision of medication for treatment and preventive services only;

there is also the to focus attention on the improvement of adherence to treatment regimen.

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17 While access and utilisation of treatment remain important, adherence to treatment has become a paramount concern for those on treatment. The efficacy of drugs depends on accurate and consistent use of prescribed regimen (Watt, Maman, Earp, Eng, Setel, Golin and Jacobson, 2009; Ammassari, Trotta, Shalev, Marconi and Antino, 2012). Non-availability and non-use of HIV and Tb drugs threaten the wellbeing of the individual and the society.

Defaulting from treatment is dangerous, with the risk of drug resistance, relapse and early death (Afolabi, Ijadunola, Fatusi and Olasode, 2009). Besides, non-adherence has public health implications, including strain on the already lean health resources and continuous spread of the diseases through contact (Omenka and Zarowsky, 2013).

Adherence is critical in the cure of Tb and management of HIV because anti-HIV and anti-Tb medications, if adhered to, can significantly reduce mortality (Vreeman, Wiehe, Ayaya, Musick and Nyandiko, 2008; Ammassari, et al., 2012). Therefore, very high levels of adherence to antiretroviral drugs and anti-tuberculosis medicines are a prerequisite for a successful and durable virological and immunological response to HIV and Tb. Low adherence increases the risk of treatment failure, disease progression and development of drug resistance (Sarna, Pujari, Sengar, Garg, Gupta, and van Dam, 2008). It is known that in antiretroviral therapy above 95 percent adherence is required for adequate virological and immunological response.

Adherence plays a critical role in the success of HIV/AIDS/Tb treatment plans, and it is the most important factor that can jeopardise expected treatment outcomes (El-Khatib, Ekstrom, Coovadia, Abrams, Petzold, Katzenstein, Morris and Kuhn, 2011).

The problem with ‗perfect‘ adherence is that it poses numerous treatment challenges to the patient, including life-long pill-taking, pill burden, frequent dosing intervals and food restrictions, among others. As a result, and because of various factors, a high number of patients do not adhere to their treatment regimen. Of course, non-adherence does not only put the infected person at risk of constant morbidity and early death but also endangers the public, as well as makes waste of limited public resources that are used in the provision of antiretroviral (ARV) drugs.

There are a number of factors that may influence adherence to treatment. These factors include perception of the threat pose by the disease (Wrubel, Moskowitz, Stephens and Johnson, 2011), benefits of medication (Bosworth, 2010), perceived side-effects, and perceived consequences of not adhering to medication (Wrubel et al. 2011). In addition, stress, attitude, motivation, social support, stigma, interaction with the medical system,

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18 culture and economic costs can all influence treatment adherence. Even though these factors have been identified, there is still considerable uncertainty about the nature of their influence on adherence to treatment.

Patients co-infected with HIV and Tb must seek separate treatment for both conditions. The treatments are either provided by two separate centres (one for HIV and the other for Tb) or in two separate departments within the same facility. As a result, patients‘ consultation days are different for HIV and Tb; some have to attend different clinic days for HIV and Tb. This is because, until recently, most nations‘ HIV and Tb programmes were mainly separate and distinct, with varying levels of interactions and communications (Tsiouris, Gandhi, El-Sadr, and Friedland, 2007). Efforts at integrating HIV and Tb treatment only began in some parts of Nigeria around 2009 with the collaboration of the United States Agency for International Development [(USAID) USAID, 2009].

The standard World Health Organisation (WHO) recommended ways of treating Tb is the Directly Observed Therapy (DOT). Adopting the DOT strategy for HIV treatment could raise the level of treatment adherence. However, separate programmes for HIV and Tb makes it difficult to attempt the DOT strategy with HIV treatment. Moreover, this strategy has the potential for improving monitoring of treatment adherence levels (US office of Global AIDS Coordinator, 2004).

With various difficulties patients face, adherence to treatment remains a key issue in HIV and Tb management. This study, therefore, examined the determinants of adherence to treatment among patients with HIV and TB in Cross River State.

1.2 Statement of the Problem

Most patients suffering from chronic diseases find it difficult to take their medications as prescribed. Poor medication adherence leads to poor treatment outcomes and unnecessary expenditure. Inability to adhere to treatment raises the question of patients‘ awareness and knowledge of the implications (to themselves and the general public) of non-adherence.

However, limited data exists on the relationship between knowledge of the implications of treatment adherence and patients‘ levels of adherence. Knowledge of the consequences of non-adherence should be a motivating factor for patients to want to act, in spite of barriers, to achieve favourable outcomes. Lack of knowledge of the implications of adherence has the

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19 potential to engender poor attitudes to treatment. In addition, patients may have poor knowledge of the lifelong nature of treatment required for HIV management (at least for the time being), and as such, get discouraged after being on treatment for sometime without being cured. Adequate research has not focused on this aspect of patient management.

The combined effect of HIV and Tb is devastatingly high; availability and access to prevention and treatment services are necessary in the fight to contain these disease conditions. The huge financial burden brought on by these diseases makes it difficult to provide adequate drugs for all infected persons. Besides, available treatment services do not get to all those that need them, and on a constant basis, as required for ARV and DOTs. This and other factors make it difficult for even those on treatment to adhere strictly to the treatment regimen. Yet, adherence to treatment is a necessary requirement in the management of HIV and the treatment of Tb to avoid relapse and early death.

Moreover, few studies have examined adherence to treatment of both HIV and Tb co-infections.

Available studies have mostly concentrated on the individual-level predictors of patients‘

adherence, such as psychological factors, personality traits, behavioural correlates, and treatment characteristics. That notwithstanding, the rate of non-adherence is likely to increase when patients are co-infected with HIV and Tb. Nigeria is currently facing a huge crisis with the continued spread of HIV and Tb epidemics. Presently, there are about 616 incidence of Tb per 100, 000 in Nigeria (UNGASS, 2007), while HIV prevalence was 1.8% in 1990, peaking at 5.8% in 2001, and fell to 4.6% in 2008 and 4.1 in 2010 [National Agency for the Control of AIDS (NACA), 2011].

The high rate of HIV and Tb infections suggests that a lot of people infected with any one of the diseases are at risk of the other. Co-infection ultimately makes adherence to treatment more problematic. HIV and Tb co-morbidity complicates treatment and makes it difficult for patients to adhere to treatment. Co-infected persons may need different clinics for the treatment of the different diseases, and this may be a very difficult process with the potential of leading to poor adherence.

Available research has not sufficiently focused attention on the interaction between the individual- and social-level factors that may hold proximal or distal relationships with treatment adherence and outcomes. Existing studies have approached adherence to treatment from the biomedical and clinical perspectives. From this perspective, experts are more concerned with

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20 the clinical manifestations of treatment failure than with social and behavioural explanation of non-adherence. As a consequence, there are gaps in knowledge of the motives and situations determining patients‘ adherence to treatment. This study was therefore designed to examine the social determinants of adherence treatment among patient with HIV and Tb co- infections in Cross River State, Nigeria.

1.3 Research Questions

The study addressed two questions:

1. What is the level of patients‘ awareness and knowledge of the implications of treatment adherence?

2. To what extent do patients co-infected with HIV and Tb adhere to their treatment and what are the factors that contribute to their level of adherence?

1.4 Objectives of the Study

The broad objective of the study was to examine the determinants adherence to treatment by HIV and Tb co-infected patients. The specific objectives were to:

1. Assess the level of patients‘ awareness and knowledge of the implications of treatment adherence.

2. Measure the level of adherence to the treatment of HIV and Tb co-infections.

3. Identify the factors determining adherence to the treatment of HIV and Tb co- infections.

1.5 Significance of the Study

Outcomes of the study contributed to a greater understanding of adherence to HIV and Tb treatment. This study characterised level of adherence on a three-level rating. These levels are: low, moderate and high adherence. Before now, most studies have depended mainly on two levels: adherent or non-adherent. This earlier categorisation was based on the belief that if a patient did not complete up to 95% of drugs, then they were not adherent. The significance of the three levels of categorisation is not only in clearly showing patients‘

treatment-taking behaviour, but also has policy implications.

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21 The policy implication of a three-level of adherence categorisation is that it is not the same level of attention and efforts are needed to scale-up adherence for patients in the various adherence levels. Besides, this study is significant because it examined HIV and Tb co- morbid patients‘ treatment adherence. Studies have concentrated on treatment behaviour for the conditions separately. By examining co-morbid patients, this study revealed the various problems that inhibit adherence on the basis of having to take medication for two chronic and stigma-inducing diseases.

This study is also useful because it stimulates, and encourages more research on adherence to the treatment of HIV and Tb by showing that it is necessary to compare adherence levels of person with only HIV or TB, and those co-infected with both. In sum, findings from this study are useful in guiding policy and strategies towards improving adherence and add to the body of knowledge available on determinants of adherence to treatment.

The study has also contributed in furthering the understanding of the usefulness of the Health Belief Model (HBM) in explaining adherence behaviour. The HBM was found to be useful for short term treatment but not for long-term treatment. Moreover, when faced with the harsh realities of stigmatisation, access problems and financial burdens, among others, perception of danger as a basic tenet of HBM can be limited in engendering appropriate health seeking behaviour.

1.6 Definitions of Concepts

Treatment Adherence: The concept ―adherence‖ is sometimes used interchangeably with

―compliance‖. Compliance carries a sense of compulsion with it as if patients may be forced by a higher authority into obedience. This notion does not suit the purpose of this study, thus, adherence was retained. For the purpose of this study, adherence to treatment was defined as the willingness to accept and start a prescribed treatment, and how closely the regimen is followed by taking drugs correctly (i.e., in the right dose, with the right frequency, and at the right time).

Self-efficacy: Self-efficacy was defined as the patient‘s belief that they were capable of organising and executing the course of action required to perform a particular activity, in this case, adhering to treatment.

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22 Stigmatisation: A situation whereby an individual or a group of people are disqualified from full social acceptance by virtue of their being infected by certain ailments, which worsen social suffering and complicates efforts to treat and control the ailment, thus, contributing to more suffering, delay in seeking help, and encourage non-adherence to treatment of those conditions.

Attitude: Attitude was defined as a disposition or tendency to respond positively or negatively towards a certain thing, idea, object, person or situation). Attitudes encompass, or are closely related to, opinions and beliefs, and are influenced by past experiences.

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CHAPTER TWO

LITERATURE REVIEW AND THEORETICAL FRAMEWORK 2.1 Literature Review

The papers that were reviewed in this study were obtained through an extensive search of the Internet using search engines such as Pub Med and Medline and library hardcopies. The search strategy involved the combination of key terms like ―tuberculosis‖, ―HIV/AIDS‖,

―treatment‖, ―adherence‖, ―compliance‖, ―access‖, ―utilisation‖, and ―integrated HIV/Tb care‖. The articles that were included in the review were those with full-text or abstracts written in English language. The literature review was undertaken to highlight the extent of scholarship and research on the issue of treatment adherence with particular attention to Tb and HIV co-infections, and to map out areas for the present research. The presentation of the review of the literature is in thematic format, based on variables emerging from the objectives of the study.

2.1 Prevalence of HIV and Tb Co-infections

The association between HIV/AIDS and Tb has been identified for a long time. HIV/AIDS and Tb co-infection has made it quite easy to assume that all persons positive for Tb must also be positive for HIV and vice verse (Bryt and Rogers, 1994). Though HIV and Tb have different risks and exposure factors, their association with each other has made the conditions more volatile. Reports from around the globe have shown that there is a high prevalence of co-infections between HIV and Tb. Research has reported that the prevalence of HIV infection among patients with Tb is 20 to 60% (Clements-Nolle, Rani, Michael, Eileen, Milton, and Mitchell, 2008). In some cases the reported prevalence suggests that one in every four Tb deaths is HIV-related; this is twice as many as previously recognised (Sharma, Mohan, and Kadhiravan, 2005).

In Nigeria, varying prevalence rates have been reported. For example, Nnorom, Esu-Williams and Tilley-Gyado (1996) in a study of the incidence of HIV, Tb and syphilis in Nigeria found that Tb prevalence increases as HIV prevalence increases. HIV epidemic therefore has grave implications for the control of tuberculosis. Nnorom et al (1996) insisted that cases of Tb within the age bracket of 16-30 should be strongly considered for HIV screening and vice

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24 versa because their data show a high prevalence of Tb and HIV among this population sub- set. Iliyasu and Babashani (2009) reported 10% while Nwachukwu and Peter (2010) found 6.4% and Pennap, Makpa, and Ogbu (2011) reported 41% prevalence of HIV in Tb patients;

According to the World Health Organisation, Tb and HIV co-infection remains a major challenge and more efforts are needed to spot and treat the two conditions in tandem. In spite of the fact that Tb kills more people with HIV than any other disease, in 2008 only 1% of people with HIV had a Tb screen (de Carvalho, Monteiro, Neto, Grangeiro and Frota, 2008).

2.1.2 Knowledge, Attitudes and Beliefs relating to Treatment

There are many studies centred on the influence of patients' understanding of treatment, (including its duration and the consequences of defaulting) on adherence to treatment (Johansson, Long, Diwan and Winkvist, 1999; Khan, Walley, Newell and Imdad, 2000;

Harper, Ahmadu, Ogden, McAdam, and Lienhardt, 2003; Jaiswal, Singh, Ogden, Porter, Sharma, Sarin, Arora and Jain, 2003; Watkins and Plant, 2004; Agu, Okojie, Oqua, King, Omonaiye, Onuoha, Isah and Iyaji, 2011). Although many of these studies were not in Nigeria, some of the findings can be useful in the examination of knowledge-related issues of treatment adherence in the present study. One important issue emerging from such studies is patients‘ poor understanding that life-long duration of treatment is required (Watkins and Plant, 2004; Estcott and Walley, 2005) while adherence is facilitated when patients understand the importance of completing treatment.

The importance of information on treatment was emphasised in a study that found non- adherent patients had little information on Tb as a disease, but were very aware of the potential adverse effects caused by its treatment (San Sebastian and Bothamley, 2000;

Olowookere, et al., 2009). Similarly, knowledge about the treatment regimen has also been explored in research on adherence. For example, a number of scholars has identified pill burden and regimen complexity as important contributors to poor adherence (Maggiolo, Ripamonti and Suter, 2003; Simoni, Frick, Pantalone and Turner, 2003; Deschamps, Graeve, Van Wijngaerden, De Saar, Vandamme, Van Vaerenbergh, Ceunen, Bobbaers, Peetermans, de Vleeschouwer and de Geest, 2004; Erah and Arute, 2008).

In a study on patients‘ preferences of treatment regimen, optimum treatment regimen that patients selected included two or less pills per day, without dietary restrictions, small pills, all drugs combined into one pill and once-a-day dosing (Maggiolo, et al., 2003). Bartlett,

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25 DeMasi, Quinn, Moxham and Rousseau (2001) showed that increased pill burden was negatively associated with the maintenance of viral suppression at 48 weeks and seemed to be the most significant predictor of response to therapy. A pill burden of up to six tablets was suitable for administration once daily, whereas twice daily therapy was preferred for a higher pill burden (Maggiolo, et al., 2003). Good adherence is associated with dosing twice a day or less (Chesney, Ickovics, Chambers, Gifford, Neidig, Zwickl and Wu, 2000; Chesney, 2003;

Orrel, Bangsberg, Badri and Wood, 2003; Ramirez and Cote, 2003).

Scheduling demands, i.e. work, difficulty fitting medication into daily routine, mealtime and food restrictions and difficult dosing schedules, are consistently associated with decreased adherence (Fogarty, Roter, Larson, Burke, Gillespie and Levy, 2002; Chesney, Chambers, Taylor and Johnson, 2003; Simoni, et al., 2003; ). This is why it is absolutely necessary that patients understand the treatment and its requirements. The use of interventions, such as pill boxes labelled with the dosing regimen and instructions, using a timer, and medication fitted into the daily schedule, can overcome some of the scheduling demands, and is associated with increased adherence (Carpenter, Cooper, Fischl, Gatell, Gazzard, Hammer, Hirsch, Jacobsen, Katzenstein, Montaner, Richman, Saag, Schechter, Schooley, Thompson, Vella, Yeni, and Volberding, 2000; Fogarty, et al., 2002).

Patients who experience difficulty with concentration or are forgetful, who have inadequate information about the regimen or who have difficulty with medication schedules, and do not understanding the relationship between adherence, viral load and disease progression, adhere significantly poorer (Wagner, 2000; Fogarty, et al., 2002; Chesney, et al., 2003). On the other hand, patients who have an accurate understanding of the purpose of the regimen are more likely to adhere to their treatment (Jones, Ishii, LaPerriere, Stanley, Antoni, Ironson, Schneiderman, Van Splunteren, Cassells, Alexander, Gousse, Vaughn, Brondolo, Tobin and Weiss, 2003). Clear, written instructions, pill boxes, asking questions about how the treatment can fit into daily activities and medication event monitoring feedbacks have been associated with improved adherence (Carpenter, et al., 2000; Fogarty, et al., 2002).

Patients‘ knowledge, attitudes, and beliefs about the disease (HIV/Tb), its treatment, and patients‘ interpretations of illness and wellness, can act as a "filter" for the information and treatment offered by the health services (Uzochukwu, Onwujekwe, Onoka, Okoli, Uguru and Chukwuogo, 2008). The influence of patients' interpretation of various illnesses on their adherence behaviour is important, and patients may interpret the themes of illness, wellness,

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26 and disease differently from health professionals. This is unlikely to be the only influence on treatment-taking, because patients‘ interpretations interact with structural and health care service factors, as well as with social context.

Knowledge is an essential component of the health behaviours of patients, especially with regard to seeking medical care for symptomatic relief. A study by Chimbanrai, Fungladda, Kaewkungwal and Silachamroon (2008) found out that knowledge was significantly associated with treatment-seeking behaviours. Patients with better knowledge of Tb were more likely to come to a hospital for a Tb clinic first than those with poorer knowledge.

Chimbanrai et al. (2008) further report that knowledge of Tb enables people to recognise the symptoms of Tb and seek early and appropriate medical care. In the same vein, Demissie, Lindtjorn and Berhane (2002) found knowledge to be an independent variable resulting in significant treatment-seeking delays. Therefore, educating people about HIV and Tb (and thus, other health conditions) will help people to seek medical care earlier.

Recent industry-supported surveys of knowledge, attitude and behaviour regarding treatment adherence have given greater insight into patient and provider perceptions of many variables influencing the practice of medicine-taking (Gallant and Block, 1998; Farthing, 2001).Such population data regarding health beliefs, self-efficacy, and barrier identification are useful for better understanding of the epidemiology treatment-taking and adherence. They are also useful in providing a context for further discussion about individual patient and provider interaction. The importance of assessing HIV educational needs has been recognised since the early 90s and researchers involved in clinical care of HIV infected patients have developed tools accordingly (Nokes, Kendrew, Rappaport, Jordan and Rivera, 1997).

Patients' beliefs about the efficacy of treatment, both positive (Marra, Marra, Cox, Palepu and Fitzgerald, 2004), and negative (Khan, et al., 2000; Demissie et al., 2003; Fong, 2004;

Greene, 2004; Khan, Walley, Witten, Shah and Javeed, 2005), may impact adherence.

Patients may question the efficacy of the pills or think that only injections are "medicine"

(Khan et al., 2005), or even question the validity of diagnostic tests that are not considered sophisticated enough for such a dangerous disease. Belief in treatment efficacy appeared to be related to patient confidence in the medical system (Munro, Lewin, Swart and Volmink, 2007a); in some cases community-based treatment programmes increased confidence among community members that Tb could be cured (Liefooghe et al., 1995). Another study noted that patients preferred to consult traditional healers (Edginton, 2002).

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27 Gauchet, Tarquinio and Fischer (2007) found adherence significantly associated with patients‘ beliefs about treatment, satisfaction with treatment, confidence in the physician, some values (―other people,‖ ―god and children‖), and duration of treatment and illness. They concluded that patients‘ beliefs about treatment are formed to a certain degree in the patients‘

relationship with the physician, and that adherence seems to be related to personal values.

Depression and stress are some of the strongest predictors of non-adherence (Fogarty, et al., 2002; Chesney, et al., 2003). A feeling of hopelessness and negative feelings reduce the motivation for self-care. Other psychological factors that have been associated with poor adherence include coping by denial and behavioural disengagement (Jones, et al., 2003). The presence of social support systems, such as supportive family members and friends (Simoni, et al., 2003) or treatment groups, peer counselling (Chesney, et al., 2003), participation in cognitive-behavioural support therapy (Jones, et al., 2003), a positive attitude to the future, long-term plans and goals, and stable mental health are consistently associated with better adherence (Fogarty, et al., 2002). It is only when people that are infected with HIV and Tb have hope, and think of a future in which they have a part to play that they will be highly motivated to follow their prescribed regimen.

Hope is a motivator and can be encouraged by the belief that outcomes are controllable (Fraser, Hadjimichael and Vollmer, 2001). In a study on the predictors of adherence to copaxone therapy, Fraser et al. (2001) saw hope as a significant predictor of adherence.

Stotland (1969) defines hope as the expectation greater than zero of achieving a goal. Hope is a primary motivator and necessary for action. Motivation is demonstrated by the individual acting toward goal attainment. Determinants of motivation include the importance of the goal and the expectation of achieving it. This can lead to the following indicators of motivation:

overt action toward the goal, covert symbolic action toward the goal, and selective attention to aspects of the environment relevant to attaining the goal. Stotland (1969) suggests that the greater the expectation of attaining a goal, the more likely the individual will act to attain it.

Therefore, it can be argued that hope for improved health and better quality of life in the future can motivate the patients to take their medication diligently, and that the hope that HIV will eventually get a cure can motivate patients to keep trying while waiting for such a time.

Investigating the individual-level factors that influence adherence to treatment has revealed a number of reasons for non-adherence. Talam, Gatongi, Rotich and Kimaiyo (2008), for example, reported keeping to clinic appointments, being away from home, forgetting, being

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28 too busy, stigma attached to ARVs, side effects, too many medicines to take, feeling sick and change in routine as contributory factors to poor adherence. Studies have shown that fear and actual experience of side effects have consistently been associated with decreased adherence, and patients who experience more than two adverse reactions are less likely to continue with the treatment (Stone, 2001). Patients may self-adjust their regimen because of side effects, toxicity or personal beliefs (Miller, 1997).

When patients self-adjust the regimen, they will be taking less than the required doses and this has serious implications for the treatment outcomes. Forgetfulness and being too busy have been cited as the most common reasons for poor adherence to medications (Ostrop, Hallert and Gill, 2000). Talam et al (2008) also posit that a change in daily routine activities of the patients contributes to poor adherence to clinic schedules. If routine activities and lifestyles of patients are associated with medication schedules, adherence to medication can easily be accommodated (Catz, 2000). Regularity of appointment is important because it is during such appointments that medicines are given, and in Nigeria, the practice is to provide medicines that can last for two weeks. It is therefore necessary for patients to keep their appointments to forestall missing their medication because they were out of stock.

Efforts have been made to determine characteristics of patients (van Dulmen et al., 2007) who are particularly likely to be non-adherent (Simoni, Frick and Huang, 2006). Factors that have been found to be associated with adherence levels include mental health problems (Mills, Nachega, Buchan, Orbinski, Attaran, Singh, Rachlis, Wu, Cooper, Thabane, Wilson, Guyatt and Bangsberg, 2006), preparation, disclosure, coping, attitude to treatment (Horne, Buick, Fisher, Leake, Cooper and Weinman, 2004), understanding (Poppa, Davidson, Deutsch, Godfrey, Fisher, Head, Horne and Sherr, 2004), and the quality of the relationship between doctor and patient (Aronson, 2007).

2.1.3 Levels of Adherence for HIV Medication

There are differing levels of adherence needed to maintain virologic suppression, depending on the ARV class used. Kobin and Sheth (2011) have found out from their systematic review of literatures that the adherence level needed for un-boosted protease inhibitors (PIs) has been established as greater than 95%, but recent studies have shown that greater than 80%

adherence to boosted PIs may be sufficient. Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) could require lower adherence rates than boosted PIs. However, study results are

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29 varied, and NNRTIs carry a potential for developing resistance with non-adherence. Studies assessing the adherence needed for raltegravir are yet to be performed.

Similarly, El-Khatib, et al. (2011) reported that unboosted protease inhibitor-based ART regimen required more than 95% adherence to ensure virologic suppression (Paterson et al., 2000). With today‘s NNRTI- and boosted protease inhibitor-based regimen a moderate adherence level (70-90%) may be adequate to achieve virologic suppression

The only concern is the availability of NNRTIs on a large scale in many developing countries. Although with funds coming from PEFFAR, these may be available with another downside to the NNRTIs that non-adherence leads quite easily to the development of resistance

2.1.4 Adherence to HIV and Tb Treatments

Several studies have been carried out in Nigeria to examine adherence levels to HIV/AIDS treatment and many other conditions requiring long-term medication taking. For example, Olowookere, Fatiregun, Akinyemi, Bamgboye and Osagbemi (2008) found out that up to 37% of respondents in a study of HIV patients did not meet 95% adherence levels, while also reporting forgetfulness and fear of toxicity of drugs as the main reason why patients reported poor adherence. Among patients co-infected with HIV and Tb, studies have reported higher default rate in Nigeria (Daniel and Oladapo, 2006; Wasiu, Asekun-Olarinmoye, Abdul- Wasiu, Olugbenga, Olarewaju and Akeem, 2011).

Uzochukwu et al (2009) have provided a deep insight into factors determining adherence to ARVs in south eastern Nigeria. Some of the most common reasons for non-adherence they reported were running out of medicines, and the inability to purchase more due to non- availability and inaccessibility to medications and financial constraints. Their findings were consistent with those found in Kano, Nigeria (Iliyasu, Kabir, Abubakar, Babashani and Zubair, 2005; Mukhtar-Yola, Adeleke, Gwarzo and Ladan, 2006). Uzochuwku et al (2009) have argued that access to medication at the treatment centres is of great concern and one of the predictors of non-adherence.

The frequent ARV drug stock-outs at several facilities in Nigeria have raised serious concerns about the sustainability of the national ARV programme and issues of non-

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30 adherence. Whenever they are out of stock for drugs, it means that some people will not receive treatment for the period the stock-out last. This would no doubt have demoralised patients and most likely shake their faith in the government and the treatment programme.

This is apart from the fact that these drugs are taken under a strict time-based regimen where 95% adherence or more is needed to effectively control viral load.

Although there is no standardised adherence measure especially in out-patients (one would have to depend on self-reported compliance), some studies have managed to do so. Current research has demonstrated that adherence to HIV remains a serious cause for worry in the course of the management of HIV and Tb morbidity and mortality. For example, Aboubacrine, Niamba, Boileau, Zunzunegui, Machouf, Nguyen and Rashed (2007) have reported that adherence to treatment remains a major public health challenge even though biological and clinical efficacy of treatment depend on strict adherence to at least three antiretroviral drugs in order to suppress replication of HIV (also see Paterson, Swindells, Mohr, Brester, Vergis, Squier, Wagener and Singh, 2000; De Ollala, Knobel, Carmona, Geula, Lopez-Colomes, Cayla, 2001; Duong, Piroth, Peytavin, Forte, Kohli, Grappin, Buisson, Chavanet and Portier 2001; McNabb, Ross, Abriola, Turley, Nightingale and Nicolau, 2001).

It is argued that missing more than 10% of doses is linked to incomplete suppression of viral replication, declining CD4 cell counts, clinical progression to AIDS or death (Paterson, et al., 2000; Press, Tyndall, Wood, Hogg and Montaner, 2002; Kuritzkes, 2004) and may even lead to the spread of drug-resistant HIV or Tb (Kuritzkes, 2004; Harrigan, Hogg, Dong, Yip, Wynhoven, Woodward, Brumme, Brumme, Mo, Alexander and Montaner, 2005). It must be noted that more recent reports stipulate 80% adherence to PI-boosted (Protease Inhibitors) and NNRTIs-based (Non-Nucleoside Reverse Transcriptase Inhibitors) regimen. However, PI-boosted and NNRTI-based regimen is not widely available in many parts of Africa.

Studies have shown differing levels of adherence needed among ARV classes of medications as a result of differing methods of adherence measurement.

According American Public Health Association (APHA) (2004), adherence is a concept with social and emotional components. It argues that if adherence is to be attained in the setting of HIV treatment, close attention must be given to the daunting regimen to which the patient is subjected to. For the patient, the ―how to‖ of adherence is the means to achieving relevant personal goals. Unless the health care provider works with the patient to identify these goals,

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31 and to understand adherence as the means to achieving them, adherence to the therapeutic regimen may be inadequate. The term ―therapeutic alliance‖ is used to describe a health care provider-patient relationship in which the therapeutic goals and the means to reach these goals are mutually affirmed and thus, most likely to be achieved (APHA, 2004).

Adherence to medication for various diseases has been the focus of many researchers and scientists long before the emergence of HIV (Cramer, Mattson, Prevey, Scheyer and Ouellette, 1989; Altice, 1998). Earlier studies on adherence to HIV medication, especially from the early HAART era, suggested that for there to viral suppression and virologic response, patients must make up to 80% or 90% adherence (Chesney, et al., 1999). However, some evidence later indicated that an 80% level with HAART adherence may be inadequate to prevent the development of antiretroviral drug resistance (Chesney, et al., 1999; Paterson, et al., 2000). This is significant in light of preliminary studies that suggest most individuals on HAART therapy are not 100% compliant. In fact, studies suggest that in a two- to three- day period, as many as 30% of patients report missing at least one dose (Chesney, 1997;

Hecht, et al., 1998). Studies among hypertensive patients report that these patients may be compliant with their medications at the 50% level and that adherence or non-adherence to medications for other diseases, as well as HIV, generally ranges from 20-80% (Ickovics, 1997; Williams and Friedland, 1997).

However, more recent studies have found different levels of adherence required for HIV management, depending on the class of ARV used. The level of adherence needed for unboosted Protease Inhibitors (PIs) has been established as greater than 95%; greater than 80% are required for booted PIs. Nonnucleside Reverse Transcriptase Inhibitors (NNRTIs) may require lower than 80% adherence rates, but has the potential to develop drug resistant if patients do not meet the required adherence (El-Khatib, et al., 2011; Kobin and Sheth, 2011) Studies examining the rate of adherence to HIV medications clearly document less than 100% adherence. For example, Muma, et al. (1995) reported adherence rates of 42%, with Chow, et al. (1993) documenting rates of 50%. Samet, Libman, Steger, Dhawan, Chen, Shevitz, Dewees-Dunk, Levenson, Kufe and Craven (1992) reported that 67% of patients were compliant at the 80% level and Eldred, Wu, Chaisson and Moore (1995) found that 46%

of their sample missed one or more doses of their medication. It is important to also note that patients may take the total number of prescribed doses, but may not take these at the appropriate times. Melbourne, Geletko, Brown, Willey-Lessne, Chase and Fisher (1999)

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32 noted that within a subgroup of patients who took more than 90% of doses, there was significant dosing fluctuation in 50% of patients during the first two months of treatment. The dosing fluctuation ranged from taking the medication within two hours of the prescribed dose time to greater than two hours of that defined time.

Even with the present day interventions to improve adherence, significant proportion of patients still do not reach the threshold necessary for viral suppression as evidenced from studies across various regions of the world. Hardly do patients attain 100% adherence and many do not reach the minimal level for reduction of viral load.

The consequences of missed doses or non-adherence to HAART appear to be severe, with evidence of an increasing viral load after missing only two days and the development of mutant viral strains (Vanhove, Schapiro, Winters, Merigan and Blaschke, 1996; Blaschke, 1997). As drug levels fall below a critical point, the regimen's inhibitory effect on viral replication may lessen, allowing for increases in viral load. This is why clinicians currently recommend that adherence be as close to 100% as possible while recognising that this recommendation poses a significant challenge to patients.

All over Africa, research is reporting poor levels of adherence to treatment of HIV (Akam, 2004; Benjaber, Rey and Himmich, 2005; Byakika-Tusiime, Oyugi, Tumwikirize, Katabira, Mugyenyi and Bangsberg, 2005). However, Biadgilign, Deribew, Amberbir and Deribe (2008) in a study in Ethiopia found that 339 children (86.9%), as reported by caregivers, were adherent to antiretroviral drugs for the past 7 days before the interview. Numerous variables were found to be significantly associated with adherence: children whose parents did not pay a fee for treatment and children who had ever received any nutritional support from the clinic were less likely to adhere. Whereas children who took co-trimoxazole medication/syrup in addition to ARVs, children who did not know their HIV status, and children who were not aware of their caregiver's health problem, were more likely to adhere than their counterparts.

The implication of Biadgilgn et al.‘s (2008) findings, especially the fact that children whose parents did not pay for the treatment are less likely to be adherent, is that whereas financial hardship is a strong factor in non-adherence, completely free provision of medication can also become a negative factor. People usually suppose that free medication is not important and thus, waste of. A good case in point is the non-acceptance of the oral polio vaccine in some parts of Nigeria.

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33 It must be reemphasised that although adherence levels are one predictor of clinical outcome, they do not always explain all the observed variations in response. Liu, Miller, Golin, Hays, Wu, Wenger and Kaplan (2006a) noted that errors in dose timing may be crucial in understanding virological response and that the percentage of doses taken is insufficient to exclusively explain outcome effects they monitored in their samples in the US (Liu, Miller, Hays, Golin, Wu, Wenger and Kaplan, 2006b). This suggests that studies examining adherence which simply utilise a recall of dose are insufficient, and a more complex measure of adherence, involving dose timing as well as adherence to circumstances of drug administration, are important for a complete and accurate measure of adherence.

Bells, Kapitao, Sikwese, van Oosterhout and Lalloo (2007) examined the rate of adherence to antiretroviral treatment among patients receiving free treatment in Malawi using MEMS cap as a ‗better‖ method of measuring adherence instead of patients self-report of adherence and pill count. Pill count dwells on the difference between number of tablets that have been taken and the number that should have been taken since that the last clinic visit. One important conclusion from the study is that there are serious complexities in the measurement of adherence and probable overestimation of adherence by pill count and self-report. Of course, these are the main methods used in the developing countries; this consequently raises concerns about the development of drug resistance

It is almost a consensus that in order to achieve an undetectable viral load and prevent the development of drug resistance, a person on HAART needs to take at least 95% of the prescribed doses on time (Paterson et al., 2000; Castro, 2005). For many people, this means taking a regimen of three antiretroviral drugs twice per day – on both occasions, they are usually taking several pills (Partners in Health, PIH, 2004). With co-infection, this number would be higher, thus doubling the pill burden.

The relationship between adherence and resistance is drug specific (Bangsberg, Moss and Deeks, 2004), There is increasing evidence that drug resistance is high among patients taking 70 – 80% of regimen containing a non-boosted protease inhibitor (i.e. regimen with no combined ritonavir). It is also high among those with intermittent or single-dose regimen of non-nucleoside reverse transcriptase inhibitors (including when nevirapine is used once to prevent mother-to-child transmission of HIV) (Castro, 2005). Ritonavir-boosted PIs (a full dose of a PI combined with ritonavir to increase the blood levels of the former) confer limited resistance, regardless of one's level of adherence (Bangsberg et al., 1999).

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34 Similarly, the key to successful tuberculosis control is patient adherence to treatment recommendations (Juvekar, Morankar, Dalai, Rangan, Khanvilkar, Vadair, Uplekar and Deshpande, 1995; White, Tulsky, Lee, Chen, Goldenson, Spetz and Kawamura, 2012).

Juvekar et al. (1995) examined connected aspects like knowledge and perceptions, attitude and beliefs, help and treatment seeking pattern of tuberculosis patients as well as the operational aspects of help seeking. They found that social stigma plays an important role in the acceptance of a disease and adherence to its treatment. A large number of patients in their study accepted that they were suffering from tuberculosis, though there were a few instances of stigmatisation by the community and denials that they had tuberculosis. Juvekar et al.‘s (1995) study also shows that patients have enough knowledge about the disease so as to recognise the symptoms and take action when they get the symptoms, but their inability to adhere to and complete the entire course of treatment is due to social, economic and health services related problems.

The administration of DOTS as opposed to self-administered Tb treatment requires the patient to appear at the DOTS centre and take the drugs in the presence and guidance of the health officers. Difficult as this may be, the DOTS therefore presents a better adherence determination than self-administered treatment. Treatment facilities in Nigeria give two weeks doses of medicines to patients so that they appear in the facility in a two weekly routine. Even so adherence to treatment in the DOTS programme is not very encouraging (Hovell, Blumberga, Gil-Trejob, Veraa, Kelleya, Sipana, Richard, Marshalld, Berge, Friedman, Catanzarog and Moser, 2003). The definition of non-adherence is varied (Albuquerque, Ximenes, Lucena-Silva, Souza, Dantas, Dantas and Rodrigues, 2007). The definitions vary for an ―unsuccessful‖ outcome of Tb treatment and the population in which it has been studied. Some definitions consider only noncompliance, while others combine all negative outcomes: treatment failure, noncompliance, and death (Paz and Siqueira, 2004;

Albuquerque, et al., 2007).

The introduction of a comprehensive multi-targeted interventionaimed at improving patient's adherence to treatment through improved counselling and communication between health staff and patients, decentralisation of treatment involving community health workers, flexibility in the choice of DOT supporter, and reinforced supervision activities of remote health posts canreduce the proportion of patients interrupting treatment before completion (Thiam, LeFevre, Hane, Ndiaye, Fatoumata, Fielding, Moustapha and Lienhardt, 2007).

DETERMINANTS OF TREATMENT ADHERENCE AMONG TUBERCULOSIS-INFECTED HIV PATIENTS IN CROSS RIVER STATE, NIGERIA

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