Modelling survival in HIV cohorts with applications to data from Zomba, Malawi
Creators: name: Singogo, Emmanuel
Publisher: name: Lancaster University
Year: 2016

description: The Human Immunodeficiency Virus (HIV) pandemic still remains a major
      public
      
      health concern worldwide. The World Health Organization (WHO) estimates
      that
      
      approximately over 70% of people living with HIV in the world are in
      sub-Saharan
      
      region. Malawi is one of the worst affected countries in sub-Saharan
      Africa with
      
      prevalence reaching up to 16% in some areas. Recent study reports, largely
      in
      
      Africa, comparing outcomes for HIV patients with Kaposi’s sarcoma (HIV/KS)
      
      and HIV patients without KS indicate poor prognosis and poor health
      outcomes
      
      amongst HIV patients with KS. While efforts are being made to improve the
      
      management and care for the HIV/KS patient group, there is also need for
      continued
      
      efforts to better understand the survival patterns in this patients. The
      work
      
      presented in this thesis attempts to investigate the survival patterns in
      different
      
      patient subgroups in HIV cohorts in Malawi by using advanced and novel
      statistical
      
      techniques with an ultimate aim of informing targeted patient treatment
      and
      
      management practices.
      
      In this thesis, we aim to address the following four objectives; (1) to
      identify
      
      risk factors for mortality among HIV patients diagnosed with Kaposi’s
      sarcoma
      
      during routine initiation of ART, (2) to model the survival pattern among
      HIV
      
      patients diagnosed with KS, (3) to model local geographical variations in
      survival
      
      among HIV patients on ART, (4) to quantify transition dynamics in HIV and
      TB
      
      co-infection using multi-state modelling.
      
      For the first two objectives, we considered extended Cox models and
      parametric
      
      models. We also used a novel approach of accounting for high attrition in
      cohorts in
      
      which we used a ’gold-standard’ data to compare survival in our cohort.
      Sensitivity
      
      analyses indicated consistencies in our approach providing an insight into
      how
      
      model results change when using this comparison approach. Overall We noted
      
      an early mortality with most patients dying in the first five months after
      starting
      
      HIV treatment. Patients with TB and the patients who started in the early
      era
      
      of 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
      parametric
      
      proportional hazards model, describe the risk of mortality in the HIV/KS
      patients
      
      well.
      
      For the third objective, spatial survival models were considered. The
      study showed
      
      existence of possible residual spatial variation in survival after
      adjusting for age,
      
      sex, KS status, TB status and unobserved individual frailties. To further
      aid our
      
      understanding, we used the choropleth maps to indicate areas with
      substantially
      
      high probability of mortality risk at different cut-off values. These
      results highlight
      
      the local geographical variations in survival in HIV populations, an
      element more
      
      often ignored in most studies on HIV data.
      
      For the last objective, we considered the homogeneous continuous time
      multistate
      
      Markov models. In this study we found that patients in TB free status had
      a
      
      relatively higher probability of transitioning to being diagnosed with TB
      compared
      
      to dying while in TB free status. However, the cumulative transition
      hazards for
      
      the ’TB free ! death’ transitions compared to the "TB free ! TB
      infection"
      
      transitions were only higher during the early days of HIV treatment. This
      result
      
      emphasize how early periods after starting HIV treatment is crucial to
      ensure
      
      better 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 and
      
      management practices of HIV patients. The findings provide clear outcome
      pathways
      
      taken by HIV/TB patients before experiencing a terminal outcome. More
      importantly, the findings could help inform policies aimed at improving
      overall
      
      survival in HIV cohorts by establishing targeted patient management and
      treatment
      
      strategies and also formulating a more efficient triage system for care
      and
      
      treatment of particular group of patients.