title: Substitution with lopinavir/ritonavir improves patient-reported outcomes including quality of life in patients who were intolerant to their antiretroviral therapy.
abstract: OBJECTIVE
  Adverse effects are important determinants of quality of life (QOL) during highly active antiretroviral therapy (HAART). The PLATO study investigated the association between changes in patient-reported outcomes including QOL and substitution with lopinavir/ritonavir in patients experiencing side effects (SEs).
  
  
  METHODS
  HIV-1-infected participants (N = 849) with undetectable viral load experiencing Grade-2 SEs of the protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) component of their HAART regimen were randomized to immediate (baseline) or deferred (week 4) substitution with lopinavir/ritonavir soft-gel capsules 400/100 mg bid. The primary endpoint was change in the total score from the AIDS Clinical Trials Group (ACTG) Symptoms Distress Module (ASDM), supplemented with two items for nephrolithiasis. Secondary endpoints included Medical Outcomes Study (MOS)-HIV scores and Center for Epidemiologic Studies-Depression (CES-D) scores.
  
  
  RESULTS
  Immediate substitution resulted in improved ASDM total score at week 4 compared with deferred substitution (p <.001) and significant improvements in all MOS-HIV domains, while significant improvement was observed in CES-D scores at week 8. Primary SEs resolved at week 8 in 65% of participants in the immediate substitution group. Suppression of HIV-1 was maintained. Treatment was well-tolerated and associated with elevations in cholesterol and triglycerides.
  
  
  CONCLUSIONS
  Substitution with LPV/r improved patient-reported outcomes including QOL in patients experiencing Grade-2 SEs, while maintaining viral suppression.
authors.affiliation: Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sprinz
authors.forename: Andrade J
authors.initials: AJ
authors.lastname: Neto
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bargman
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Green
authors.forename: Michelle P
authors.initials: MP
authors.lastname: Luo
authors.forename: Jacquelyn R
authors.initials: JR
authors.lastname: Sylte
authors.forename: Florence I
authors.initials: FI
authors.lastname: McMillan
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: King
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rode
authors.forename: Scott C
authors.initials: SC
authors.lastname: Brun
authors.forename: George J
authors.initials: GJ
authors.lastname: Hanna
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Podsadecki
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011744:Pyrimidinones / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir