title: Determinants of time to antiretroviral treatment initiation and subsequent mortality on treatment in a cohort in rural northern Malawi.
abstract: BACKGROUND
  To optimise care HIV patients need to be promptly initiated on antiretroviral therapy (ART) and subsequently retained on treatment. In this study we report on the interval between enrolment and treatment initiation, and investigate subsequent attrition and mortality of patients on ART at a rural clinic in Malawi.
  
  
  METHODS
  HIV-positive individuals were recruited to a cohort study between January 2008 and August 2011 at Chilumba Rural Hospital (CRH). Outcomes were ascertained, up to 7 years after enrolment, through follow-up and by linkage to ART registers and the Karonga Health and Demographic Surveillance System (KHDSS). Kaplan-Meier methods and Cox regression were used to examine ART initiation after enrolment, mortality after ART initiation, and attrition after ART initiation.
  
  
  RESULTS
  Of the 617 individuals recruited, 523 initiated ART between January 2008 and January 2015. Median time from HIV testing to commencement of ART was 59 days (IQR: 10-330). By a year after enrolment 74.2 % (95 % CI 70.6-77.7 %) had initiated ART. Baseline clinical data at ART initiation and data on attrition was only available for the 438 individuals who initiated ART during active follow-up, between January 2008 and August 2011. Of these individuals, 6 were missing Ministry of Health numbers, leaving 432 included in analyses of attrition and mortality. At 4 years after ART initiation 71.3 % (95 % CI 65.7-76.2 %) of these patients were retained on treatment at the CRH and 17.2 % (95 % CI 13.8-21.4 %) had died. Participants who had a lower CD4 count at enrolment (≤350 cells/μl), enrolled in 2008, or tested for HIV at the CRH rather than through serosurveys, initiated treatment faster. Once on treatment, mortality rates were higher in patients who were HIV tested at the CRH, male, older (≥35 years), missing a CD4 count, or underweight (BMI < 18.5) at ART initiation.
  
  
  CONCLUSIONS
  Through linkage to the KHDSS and ART registers it was possible to continue follow-up beyond the end of the initial cohort study. Annual mortality after ART initiation remained considerable over a period of 4 years. Greater access to HIV and CD4 testing alongside initiation at higher CD4 counts, as planned in the test and treat strategy, could reduce this mortality.
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Jeremy Philip
authors.initials: JP
authors.lastname: Brown
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK ; Karonga Prevention Study, Chilumba, Malawi.
authors.forename: Bagrey
authors.initials: B
authors.lastname: Ngwira
authors.affiliation: Karonga Prevention Study, Chilumba, Malawi ; Centre for Neglected Tropical Diseases, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Terence
authors.initials: T
authors.lastname: Tafatatha
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK ; Karonga Prevention Study, Chilumba, Malawi.
authors.forename: Amelia Catharine
authors.initials: AC
authors.lastname: Crampin
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK ; Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: French
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK ; Karonga Prevention Study, Chilumba, Malawi.
authors.forename: Olivier
authors.identifier: 0000-0002-1122-5382
authors.initials: O
authors.lastname: Koole
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D057210:Delayed Diagnosis / Q000401:mortality / Q000706:statistics & numerical data*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D059012:Lost to Follow-Up; D008295:Malawi / Q000453:epidemiology; D008297:Male; D016016:Proportional Hazards Models; D012424:Rural Population / Q000706:statistics & numerical data*; D013997:Time Factors; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents
keywords: ART; Attrition; CD4 count; HIV; HIV testing; Malawi; Mortality; Sub-Saharan Africa