title: Duration of Antiretroviral Therapy Adherence Interruption Is Associated With Risk of Virologic Rebound as Determined by Real-Time Adherence Monitoring in Rural Uganda.
abstract: BACKGROUND
  Antiretroviral therapy (ART) adherence interruptions have been associated with viral rebound; however, the true risk is unknown because HIV RNA has never been measured during ongoing interruptions.
  
  
  METHODS
  The Uganda AIDS Rural Treatment Outcomes Study is an observational longitudinal cohort of adults initiating ART. We monitored adherence with the device that wirelessly transmits records of device openings, and routinely assessed HIV RNA quarterly. When lapses of 48+ hours between device openings were detected, we made unannounced visits to participants to investigate the cause and assess HIV RNA. Generalized estimating equation logistic regressions were used to assess factors associated with viral rebound.
  
  
  RESULTS
  We followed 479 participants (median: 25 months per participant). Most were women (72%), median age was 36 years, median pre-ART CD4 count was 198 cells per microliter, median pre-ART HIV RNA level was 5.0 log10 copies per milliliter, and median duration of prior viral suppression was 13 months. A total of 587 adherence interruptions followed confirmed prior viral suppression, of which 13 (2%) had detectable viral rebound. Viral rebound was associated with duration of adherence interruption (odds ratio: 1.25 for each day beyond 48 hours; P = 0.007) and 30-day adherence before the interruption (odds ratio: 0.73; P = 0.02).
  
  
  CONCLUSIONS
  This article is the first demonstration of HIV RNA rebound during adherence interruptions objectively measured in real time. Odds of viral rebound increased by 25% with each day beyond 48 hours. Real-time adherence monitoring was feasible in a sub-Saharan African setting. Further research should assess the potential for real-time adherence interventions to sustain adherence to affordable first-line regimens.
authors.affiliation: *Center for Global Health, Massachusetts General Hospital, Boston, MA; †Department of Medicine, Harvard Medical School, Boston, MA; ‡Global Health Collaboration, Mbarara University of Science and Technology, Mbarara, Uganda; §EpiCentre/Médecins Sans Frontières, Mbarara, Uganda; ‖Department of Medical Laboratory Sciences, Mbarara University of Science and Technology, Mbarara, Uganda; Departments of ¶Epidemiology and Biostatistics; #Medicine, University of California, San Francisco, CA; and **Department of Global Health and Populations, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Haberer
authors.forename: Nicholas
authors.initials: N
authors.lastname: Musinguzi
authors.forename: Yap
authors.initials: Y
authors.lastname: Boum
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Siedner
authors.forename: A Rain
authors.initials: AR
authors.lastname: Mocello
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
mesh_terms: D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D055118:Medication Adherence; D012367:RNA, Viral / Q000097:blood*; D012424:Rural Population; D013997:Time Factors; D016896:Treatment Outcome; D014454:Uganda; D019562:Viral Load; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral