title: Joint longitudinal data analysis in detecting determinants of CD4 cell count change and adherence to highly active antiretroviral therapy at Felege Hiwot Teaching and Specialized Hospital, North-west Ethiopia (Amhara Region).
abstract: BACKGROUND
  Adherence and CD4 cell count change measure the progression of the disease in HIV patients after the commencement of HAART. Lack of information about associated factors on adherence to HAART and CD4 cell count reduction is a challenge for the improvement of cells in HIV positive adults. The main objective of adopting joint modeling was to compare separate and joint models of longitudinal repeated measures in identifying long-term predictors of the two longitudinal outcomes: CD4 cell count and adherence to HAART.
  
  
  METHODS
  A longitudinal retrospective cohort study was conducted to examine the joint predictors of CD4 cell count change and adherence to HAART among HIV adult patients enrolled in the first 10 months of the year 2008 and followed-up to June 2012. Joint model was employed to determine joint predictors of two longitudinal response variables over time. Furthermore, the generalized linear mixed effect model had been used for specification of the marginal distribution, conditional to correlated random effect.
  
  
  RESULTS
  A total of 792 adult HIV patients were studied to analyze the longitudinal joint model study. The result from this investigation revealed that age, weight, baseline CD4 cell count, ownership of cell phone, visiting times, marital status, residence area and level of disclosure of the disease to family members had significantly affected both outcomes. From the two-way interactions, time * owner of cell phone, time * sex, age * sex, age * level of education as well as time * level of education were significant for CD4 cell count change in the longitudinal data analysis. The multivariate joint model with linear predictor indicates that CD4 cell count change was positively correlated (p ≤ 0.0001) with adherence to HAART. Hence, as adherence to HAART increased, CD4 cell count also increased; and those patients who had significant CD4 cell count change at each visiting time had been encouraged to be good adherents.
  
  
  CONCLUSIONS
  Joint model analysis was more parsimonious as compared to separate analysis, as it reduces type I error and subject-specific analysis improved its model fit. The joint model operates multivariate analysis simultaneously; and it has great power in parameter estimation. Developing joint model helps validate the observed correlation between the outcomes that have emerged from the association of intercepts. There should be a special attention and intervention for HIV positive adults, especially for those who had poor adherence and with low CD4 cell count change. The intervention may be important for pre-treatment counseling and awareness creation. The study also identified a group of patients who were with maximum risk of CD4 cell count change. It is suggested that this group of patients needs high intervention for counseling.
authors.affiliation: Department of Statistics, Bahir Dar University, Bahir Dar, Ethiopia. bisrategebrail@yahoo.com.
authors.forename: Awoke
authors.initials: A
authors.lastname: Seyoum
authors.affiliation: Department of Statistics, UNISA, Pretoria, South Africa.
authors.forename: Principal
authors.initials: P
authors.lastname: Ndlovu
authors.affiliation: School of Mathematics, Statistics and Computer Science, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Zewotir
authors.initials: Z
authors.lastname: Temesgen
mesh_terms: D000328:Adult; D000367:Age Factors; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001835:Body Weight; D018791:CD4 Lymphocyte Count / Q000379:methods* / Q000706:statistics & numerical data; D040421:Cell Phone; D003376:Counseling; D018450:Disease Progression; D005002:Ethiopia; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006782:Hospitals, Special; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012737:Sex Factors; D013223:Statistics as Topic
chemical_list: D019380:Anti-HIV Agents
keywords: Adherence; CD4 cell count change; HAART; Joint model; Multivariate longitudinal data