TY - BOOK

T1 - Modelling survival in HIV cohorts with applications to data from Zomba, Malawi

AU - Singogo, Emmanuel

PY - 2016

Y1 - 2016

N2 - The Human Immunodeficiency Virus (HIV) pandemic still remains a major publichealth concern worldwide. The World Health Organization (WHO) estimates thatapproximately over 70% of people living with HIV in the world are in sub-Saharanregion. Malawi is one of the worst affected countries in sub-Saharan Africa withprevalence reaching up to 16% in some areas. Recent study reports, largely inAfrica, comparing outcomes for HIV patients with Kaposi’s sarcoma (HIV/KS)and HIV patients without KS indicate poor prognosis and poor health outcomesamongst HIV patients with KS. While efforts are being made to improve themanagement and care for the HIV/KS patient group, there is also need for continuedefforts to better understand the survival patterns in this patients. The workpresented in this thesis attempts to investigate the survival patterns in differentpatient subgroups in HIV cohorts in Malawi by using advanced and novel statisticaltechniques with an ultimate aim of informing targeted patient treatment andmanagement practices.In this thesis, we aim to address the following four objectives; (1) to identifyrisk factors for mortality among HIV patients diagnosed with Kaposi’s sarcomaduring routine initiation of ART, (2) to model the survival pattern among HIVpatients diagnosed with KS, (3) to model local geographical variations in survivalamong HIV patients on ART, (4) to quantify transition dynamics in HIV and TBco-infection using multi-state modelling.For the first two objectives, we considered extended Cox models and parametricmodels. We also used a novel approach of accounting for high attrition in cohorts inwhich we used a ’gold-standard’ data to compare survival in our cohort. Sensitivityanalyses indicated consistencies in our approach providing an insight into howmodel results change when using this comparison approach. Overall We notedan early mortality with most patients dying in the first five months after startingHIV treatment. Patients with TB and the patients who started in the early eraof ART were significantly at risk of dying. The model diagnostics indicated that(i) a random effects Cox/Log-Gaussian frailty model and (ii) a flexible parametricproportional hazards model, describe the risk of mortality in the HIV/KS patientswell.For the third objective, spatial survival models were considered. The study showedexistence of possible residual spatial variation in survival after adjusting for age,sex, KS status, TB status and unobserved individual frailties. To further aid ourunderstanding, we used the choropleth maps to indicate areas with substantiallyhigh probability of mortality risk at different cut-off values. These results highlightthe local geographical variations in survival in HIV populations, an element moreoften ignored in most studies on HIV data.For the last objective, we considered the homogeneous continuous time multistateMarkov models. In this study we found that patients in TB free status had arelatively higher probability of transitioning to being diagnosed with TB comparedto dying while in TB free status. However, the cumulative transition hazards forthe ’TB free ! death’ transitions compared to the "TB free ! TB infection"transitions were only higher during the early days of HIV treatment. This resultemphasize how early periods after starting HIV treatment is crucial to ensurebetter prognosis. We also noted significant gender differences in the ’TB-free !death’ transitions.It is anticipated that the findings in this thesis will help to inform treatment andmanagement practices of HIV patients. The findings provide clear outcome pathwaystaken by HIV/TB patients before experiencing a terminal outcome. More importantly, the findings could help inform policies aimed at improving overallsurvival in HIV cohorts by establishing targeted patient management and treatmentstrategies and also formulating a more efficient triage system for care andtreatment of particular group of patients.

AB - The Human Immunodeficiency Virus (HIV) pandemic still remains a major publichealth concern worldwide. The World Health Organization (WHO) estimates thatapproximately over 70% of people living with HIV in the world are in sub-Saharanregion. Malawi is one of the worst affected countries in sub-Saharan Africa withprevalence reaching up to 16% in some areas. Recent study reports, largely inAfrica, comparing outcomes for HIV patients with Kaposi’s sarcoma (HIV/KS)and HIV patients without KS indicate poor prognosis and poor health outcomesamongst HIV patients with KS. While efforts are being made to improve themanagement and care for the HIV/KS patient group, there is also need for continuedefforts to better understand the survival patterns in this patients. The workpresented in this thesis attempts to investigate the survival patterns in differentpatient subgroups in HIV cohorts in Malawi by using advanced and novel statisticaltechniques with an ultimate aim of informing targeted patient treatment andmanagement practices.In this thesis, we aim to address the following four objectives; (1) to identifyrisk factors for mortality among HIV patients diagnosed with Kaposi’s sarcomaduring routine initiation of ART, (2) to model the survival pattern among HIVpatients diagnosed with KS, (3) to model local geographical variations in survivalamong HIV patients on ART, (4) to quantify transition dynamics in HIV and TBco-infection using multi-state modelling.For the first two objectives, we considered extended Cox models and parametricmodels. We also used a novel approach of accounting for high attrition in cohorts inwhich we used a ’gold-standard’ data to compare survival in our cohort. Sensitivityanalyses indicated consistencies in our approach providing an insight into howmodel results change when using this comparison approach. Overall We notedan early mortality with most patients dying in the first five months after startingHIV treatment. Patients with TB and the patients who started in the early eraof ART were significantly at risk of dying. The model diagnostics indicated that(i) a random effects Cox/Log-Gaussian frailty model and (ii) a flexible parametricproportional hazards model, describe the risk of mortality in the HIV/KS patientswell.For the third objective, spatial survival models were considered. The study showedexistence of possible residual spatial variation in survival after adjusting for age,sex, KS status, TB status and unobserved individual frailties. To further aid ourunderstanding, we used the choropleth maps to indicate areas with substantiallyhigh probability of mortality risk at different cut-off values. These results highlightthe local geographical variations in survival in HIV populations, an element moreoften ignored in most studies on HIV data.For the last objective, we considered the homogeneous continuous time multistateMarkov models. In this study we found that patients in TB free status had arelatively higher probability of transitioning to being diagnosed with TB comparedto dying while in TB free status. However, the cumulative transition hazards forthe ’TB free ! death’ transitions compared to the "TB free ! TB infection"transitions were only higher during the early days of HIV treatment. This resultemphasize how early periods after starting HIV treatment is crucial to ensurebetter prognosis. We also noted significant gender differences in the ’TB-free !death’ transitions.It is anticipated that the findings in this thesis will help to inform treatment andmanagement practices of HIV patients. The findings provide clear outcome pathwaystaken by HIV/TB patients before experiencing a terminal outcome. More importantly, the findings could help inform policies aimed at improving overallsurvival in HIV cohorts by establishing targeted patient management and treatmentstrategies and also formulating a more efficient triage system for care andtreatment of particular group of patients.

U2 - 10.17635/lancaster/thesis/95

DO - 10.17635/lancaster/thesis/95

M3 - Doctoral Thesis

PB - Lancaster University

ER -