title: Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.
abstract: Practical issues, including cost, hinder implementing virologic monitoring of patients on antiretroviral therapy (ART) in resource-limited settings. We evaluated factors that might guide monitoring frequency and efforts to prevent treatment failure after initial virologic suppression.
  
  
  
  Participants were the 911 HIV-infected antiretroviral-naïve adults with CD4 count <300 cells/μL who started efavirenz-based ART in the international A5175/PEARLS trial and achieved HIV-1 RNA <1000 copies/mL at 24 weeks. Participant report of ART adherence was evaluated using a structured questionnaire in monthly interviews. Adherence and readily available clinical and laboratory measures were evaluated as predictors of late virologic failure (late VF: confirmed HIV-1 RNA ≥1000 copies/mL after 24 weeks).
  
  
  
  During median follow-up of 3.5 years, 82/911 participants (9%) experienced late VF. Of 516 participants reporting missed doses during the first 24 weeks of ART, 55 (11%) experienced late VF, compared with 27 (7%) of 395 participants reporting no missed doses (hazard ratio: 1.73; 95% CI: 1.08, 2.73). This difference persisted in multivariable analysis, in which lower pre-ART hemoglobin and absence of Grade ≥3 laboratory results prior to week 24 were also associated with higher risk of late VF.
  
  
  
  In this clinical trial, the late VF rate after successful suppression was very low. If achievable in routine clinical practice, virologic monitoring involving infrequent (e.g. annual) measurements might be considered; the implications of this for development of resistance need evaluating. Patients reporting missed doses early after ART initiation, despite achieving initial suppression, might require more frequent measurement and/or strategies for promoting adherence.
authors.affiliation: a Johns Hopkins Research Project , Blantyre , Malawi.
authors.forename: Isaac
authors.initials: I
authors.lastname: Singini
authors.affiliation: b Department of Medicine/Division of Infectious Diseases , University of Colorado School of Medicine , Aurora , CO , USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Campbell
authors.affiliation: c Center for Biostatistics in AIDS Research , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Smeaton
authors.affiliation: d Chennai Antiviral Research and Treatment (CART) CRS , YRGCARE Medical Centre , Chennai , India.
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.affiliation: e Therapeutic Research , Asociacion Civil Impacta Salud y Educacion , Lima , Peru.
authors.forename: Alberto
authors.initials: A
authors.lastname: La Rosa
authors.affiliation: f Research Institute for Health Sciences , Chiang Mai University , Chiang Mai , Thailand.
authors.forename: Sineenart
authors.initials: S
authors.lastname: Taejareonkul
authors.affiliation: g Department of Psychology , University of Miami , Miami , FL , USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Safren
authors.affiliation: h Miriam Hospital, Brown University , Providence , RI , USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Flanigan
authors.affiliation: i University of Zimbabwe College of Health Sciences , Harare , Zimbabwe.
authors.forename: James G
authors.initials: JG
authors.lastname: Hakim
authors.affiliation: c Center for Biostatistics in AIDS Research , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughes
keywords: Adherence; Antiretroviral therapy; Resource-limited settings; Viral load monitoring; Virologic failure; Virologic suppression