Improving linkage into HIV care among adults in Blantyre, Malawi Thesis submitted in accordance with the requirements of the University of Liverpool for the degree of Doctor in Philosophy by Peter MacPherson March 2013 2 Preface | My role I, Peter MacPherson, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. My Role I conducted the background literature review and systematic literature review of studies reporting on the linkage into HIV care. Chigomezgo Munthali and I conducted the systematic review of the diagnostic accuracy of the WHO clinical staging system; I performed the meta-analysis. I designed the study protocols and questionnaires for the prospective cohort study, qualitative study, cluster randomised trial and diagnostic accuracy studies with input from Liz Corbett, David Lalloo, Bertie Squire and Gillian Mann. I wrote all study standard operating procedures, except for the standard operating procedures, for laboratory measurement of CD4 count, which were written by Aaron Mdolo. I recruited and trained the Research Assistants and Study Nurses who conducted the prospective cohort study, qualitative study and the home initiation of HIV care and ascertainment of facility outcome components of the cluster randomised trial. Liz Corbett’s HitTB study team recruited and trained Field Workers who performed mapping, household enumeration and the demographic census for the cluster- randomised trial. Community Counsellors who provided home-based HIV self-testing (HIVST), recorded uptake of HIVST and reporting of HIVST results were recruited, trained and supervised by the HitTB study team. Aaron Mdolo and his laboratory team performed laboratory analysis of CD4 counts. Data management was performed by myself and the HitTB study team, supervised by Augustine Choko and Deus Thindwa. Data cleaning was performed by myself with support from the HitTB study team. I wrote the statistical analysis plan for the cluster-randomised trial, with input from Liz Corbett and Emily Webb. I analysed the data for the prospective cohort study. Emily Webb 3 Preface | My role wrote do-files for analysis of the baseline census for the HitTB study and I modified these to analyse the baseline census for the home initiation of HIV care trial. I wrote programmes to analyse the data for the endpoint analysis of the cluster randomised trial, with support from Emily Webb and Richard Hayes. The interview guides for the qualitative study were designed by me, with input from Liz Corbett, Nic Desmond, Eleanor MacPherson and Daniel Mwale. Daniel Mwale conducted qualitative interviews. I designed the coding framework and socio-ecological model. I analysed qualitative data, with input from Liz Corbett, Eleanor MacPherson and Daniel Mwale. 4 Preface | Table of contents Table of Contents My Role ............................................................................................................................... 3 Table of Contents ................................................................................................................ 5 List of Tables ..................................................................................................................... 12 List of Figures .................................................................................................................... 14 List of Acronyms ................................................................................................................ 16 List of Supporting Manuscripts ......................................................................................... 18 Abstract ............................................................................................................................. 20 Acknowledgements ........................................................................................................... 23 1. Introduction ............................................................................................................... 25 1.1. Background ........................................................................................................ 25 1.2. Project starting points ........................................................................................ 27 1.3. Aims and objectives ............................................................................................ 28 1.4. Outline of thesis ................................................................................................. 29 2. Literature review ........................................................................................................ 31 2.1. Human Immunodeficiency Virus Infection ......................................................... 31 2.1.1. Origins of the HIV pandemic ........................................................................ 31 2.1.2. Modes of transmission of HIV infection and prevention ............................. 33 2.1.3. Risk factors for HIV transmission and prevention strategies ....................... 35 2.1.4. Pathogenesis and natural history of HIV infection ...................................... 41 2.1.5. Global and sub-Saharan African epidemiology of HIV ................................. 45 2.1.6. HIV epidemiology in Malawi ........................................................................ 47 2.2. HIV testing and Counselling ................................................................................ 50 2.2.1. Objectives of HIV testing and counseling .................................................... 50 2.2.2. HIV testing technologies .............................................................................. 52 2.2.3. Uptake of HIV testing and counselling ......................................................... 53 2.2.4. Models of HIV testing and counselling ........................................................ 55 2.2.5. Facility-based approaches to HTC ................................................................ 56 2.2.6. Community-based approaches to HTC ........................................................ 62 2.2.7. HIV self-testing ............................................................................................ 65 5 Preface | Table of contents 2.2.8. Which models of HTC are recommended? ................................................. 71 2.2.9. HIV testing in Malawi .................................................................................. 72 2.3. Treatment of HIV infection ................................................................................ 74 2.3.1. Antiretroviral therapy for treatment of HIV infection ................................. 74 2.4. Assessment of eligibility for antiretroviral therapy ........................................... 80 2.4.1. When to start antiretroviral therapy? ......................................................... 80 2.4.2. Measurement of CD4 count to determine ART eligibility ........................... 82 2.4.3. Clinical staging assessments for ART eligibility ........................................... 83 2.4.4. Alternative approaches to assessing ART eligibility .................................... 90 2.5. The public health approach to scale-up of ART delivery in low income countries with generalised HIV epidemics ......................................................................... 93 2.6. The National ART programme in Malawi ......................................................... 100 2.7. Linkage between HIV diagnosis and initiation of ART ...................................... 104 2.7.1. The HIV care cascade ................................................................................ 104 2.7.2. Defining linkage into care .......................................................................... 107 2.7.3. Linkage and retention between HIV diagnosis and initiation of ART ........ 111 2.7.4. Summary estimates for pre-treatment patient loss to care ..................... 119 2.7.5. Reasons for pre-treatment loss to follow-up ............................................ 123 2.7.6. Interventions to improve linkage and retention between HIV diagnosis and initiation of ART ........................................................................................ 127 2.8. Development of a conceptual framework to understand pre-treatment loss to care in the HIV care cascade ............................................................................ 132 2.8.1. Summary of evidence regarding magnitude, reasons for, consequences and potential areas for intervention to improve pre-treatment loss to care .. 134 2.9. Measurement of household poverty status .................................................... 136 2.9.1. Poverty, illness and health ........................................................................ 136 2.9.2. Measuring poverty in resource limited settings – the proxy means test method ..................................................................................................... 137 2.10. Malawi .............................................................................................................. 140 2.10.1. Geopolitical and socioeconomic indicators ............................................... 140 3. Methods .................................................................................................................. 143 3.1. Study location and population ......................................................................... 143 6 Preface | Table