title: Not all missed doses are the same: sustained NNRTI treatment interruptions predict HIV rebound at low-to-moderate adherence levels.
abstract: BACKGROUND
  While the relationship between average adherence to HIV potent antiretroviral therapy is well defined, the relationship between patterns of adherence within adherence strata has not been investigated. We examined medication event monitoring system (MEMS) defined adherence patterns and their relation to subsequent virologic rebound.
  
  
  RESULTS
  We selected subjects with at least 3-months of previous virologic suppression on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen from two prospective cohorts in France and North America. We assessed the risk of virologic rebound, defined as HIV RNA of >400 copies/mL according to several MEMS adherence measurements. Seventy two subjects were studied, five of them experienced virologic rebound. Subjects with and without virologic rebound had similar baseline characteristics including treatment durations, regimen (efavirenz vs nevirapine), and dosing schedule. Each 10% increase in average adherence decreased the risk of virologic rebound (OR = 0.56; 95% confidence interval (CI) [0.37, 0.81], P<0.002). Each additional consecutive day off therapy for the longest treatment interruption (OR = 1.34; 95%CI [1.15, 1.68], P<0.0001) and each additional treatment interruption for more than 2 days (OR = 1.38; 95%CI [1.13, 1.77], P<0.002) increased the risk of virologic rebound. In those with low-to-moderate adherence (i.e. <80%), treatment interruption duration (16.2 days versus 6.1 days in the control group, P<0.02), but not average adherence (53.1% vs 55.9%, respectively, P = 0.65) was significantly associated with virologic rebound.
  
  
  CONCLUSIONS
  Sustained treatment interruption may pose a greater risk of virologic rebound on NNRTI therapy than the same number of interspersed missed doses at low-to-moderate adherence.
authors.affiliation: Clinical Research and Biostatistics Department, Côte de Nacre University Hospital, Caen, France. parienti-jj@chu-caen.fr
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Parienti
authors.forename: Moupali
authors.initials: M
authors.lastname: Das-Douglas
authors.forename: Véronique
authors.initials: V
authors.lastname: Massari
authors.forename: David
authors.initials: D
authors.lastname: Guzman
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Renaud
authors.initials: R
authors.lastname: Verdon
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006678:HIV / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010349:Patient Compliance; D012367:RNA, Viral / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors