title: Psychosocial predictors of non-adherence and treatment failure in a large scale multi-national trial of antiretroviral therapy for HIV: data from the ACTG A5175/PEARLS trial.
abstract: BACKGROUND
  PEARLS, a large scale trial of antiretroviral therapy (ART) for HIV (n = 1,571, 9 countries, 4 continents), found that a once-daily protease inhibitor (PI) based regimen (ATV+DDI+FTC), but not a once-daily non-nucleoside reverse transcriptase inhibitor/nucleoside reverse transcriptase inhibitor (NNRTI/NRTI) regimen (EFV+FTC/TDF), had inferior efficacy compared to a standard of care twice-daily NNRTI/NRTI regimen (EFV+3TC/ZDV). The present study examined non-adherence in PEARLS.
  
  
  METHODS
  Outcomes: non-adherence assessed by pill count and by self-report, and time to treatment failure. Longitudinal predictors: regimen, quality of life (general health perceptions  =  QOL-health, mental health  =  QOL-mental health), social support, substance use, binge drinking, and sexual behaviors. "Life-Steps" adherence counseling was provided.
  
  
  RESULTS
  In both pill-count and self-report multivariable models, both once-a-day regimens had lower levels of non-adherence than the twice-a-day standard of care regimen; although these associations attenuated with time in the self-report model. In both multivariable models, hard-drug use was associated with non-adherence, living in Africa and better QOL-health were associated with less non-adherence. According to pill-count, unprotected sex was associated with non-adherence. According to self-report, soft-drug use was associated with non-adherence and living in Asia was associated with less non-adherence. Both pill-count (HR = 1.55, 95% CI: 1.15, 2.09, p<.01) and self-report (HR = 1.13, 95% CI: 1.08, 1.13, p<.01) non-adherence were significant predictors of treatment failure over 72 weeks. In multivariable models (including pill-count or self-report nonadherence), worse QOL-health, age group (younger), and region were also significant predictors of treatment failure.
  
  
  CONCLUSIONS
  In the context of a large, multi-national, multi-continent, clinical trial there were variations in adherence over time, with more simplified regimens generally being associated with better adherence. Additionally, variables such as QOL-health, regimen, drug-use, and region play a role. Self-report and pill-count adherence, as well as additional psychosocial variables, such QOL-health, age, and region, were, in turn, associated with treatment failure.
authors.affiliation: Massachusetts General Hospital, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America; The Fenway Institute, Fenway Health, Boston, MA, United States of America.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Safren
authors.affiliation: The Fenway Institute, Fenway Health, Boston, MA, United States of America; Harvard School of Public Health, Boston, MA, United States of America.
authors.forename: Katie B
authors.initials: KB
authors.lastname: Biello
authors.affiliation: Harvard School of Public Health, Boston, MA, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Smeaton
authors.affiliation: Massachusetts General Hospital, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America; The Fenway Institute, Fenway Health, Boston, MA, United States of America; Harvard School of Public Health, Boston, MA, United States of America.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Mimiaga
authors.affiliation: Frontier Science and Technology Research Foundation, Amherst, NY, United States of America.
authors.forename: Ann
authors.initials: A
authors.lastname: Walawander
authors.affiliation: Asociacion Civil Impacta Salud y Educacion, Lima, Peru.
authors.forename: Javier R
authors.initials: JR
authors.lastname: Lama
authors.affiliation: Alpert Medical School/The Miriam Hospital, Providence, RI, United States of America.
authors.forename: Aadia
authors.initials: A
authors.lastname: Rana
authors.affiliation: College of Medicine - Johns Hopkins Research Project, Blantyre, Malawi.
authors.forename: Mulinda
authors.initials: M
authors.lastname: Nyirenda
authors.affiliation: University of North Carolina Project, Lilongwe, Malawi.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Kayoyo
authors.affiliation: University of Zimbabwe-University of California San Francisco Collaborative Research Program, Harare, Zimbabwe.
authors.forename: Wadzanai
authors.initials: W
authors.lastname: Samaneka
authors.affiliation: National AIDS Research Institute, Pune, India.
authors.forename: Anjali
authors.initials: A
authors.lastname: Joglekar
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Celentano
authors.affiliation: NIH/NIAD/DAIDS Pharmaceutical Affairs, Bethesda, MD, United States of America.
authors.forename: Ana
authors.initials: A
authors.lastname: Martinez
authors.affiliation: Massachusetts General Hospital, Boston, MA, United States of America.
authors.forename: Jocelyn E
authors.initials: JE
authors.lastname: Remmert
authors.affiliation: Frontier Science and Technology Research Foundation, Amherst, NY, United States of America.
authors.forename: Aspara
authors.initials: A
authors.lastname: Nair
authors.affiliation: Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, S. Africa.
authors.forename: Umesh G
authors.initials: UG
authors.lastname: Lalloo
authors.affiliation: YRGCARE Medical Centre, Chennai, India.
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.affiliation: University of Zimbabwe, Harare, Zimbabwe, Africa.
authors.forename: James
authors.initials: J
authors.lastname: Hakim
authors.affiliation: University of Colorado Denver, Aurora, CO, United States of America.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Campbell
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D010349:Patient Compliance / Q000523:psychology*; D011584:Psychology; D011788:Quality of Life; D012944:Social Support; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents