title: Adherence to drug-refill is a useful early warning indicator of virologic and immunologic failure among HIV patients on first-line ART in South Africa.
abstract: BACKGROUND
  Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa.
  
  
  METHODS
  In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12-99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO).
  
  
  RESULTS
  After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2-6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2-3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02).
  
  
  CONCLUSIONS
  One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure.
authors.affiliation: Division of Global Health (IHCAR), Karolinska Institutet, Stockholm, Sweden. ziad.khatib@gmail.com
authors.forename: Ziad
authors.initials: Z
authors.lastname: El-Khatib
authors.forename: David
authors.initials: D
authors.lastname: Katzenstein
authors.forename: Gaetano
authors.initials: G
authors.lastname: Marrone
authors.forename: Fatima
authors.initials: F
authors.lastname: Laher
authors.forename: Lerato
authors.initials: L
authors.lastname: Mohapi
authors.forename: Max
authors.initials: M
authors.lastname: Petzold
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Anna Mia
authors.initials: AM
authors.lastname: Ekström
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003710:Demography; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D057566:Self Report; D013019:South Africa; D017211:Treatment Failure; D055815:Young Adult