title: Lopinavir/Ritonavir Monotherapy as Second-line Antiretroviral Treatment in Resource-Limited Settings: Week 104 Analysis of AIDS Clinical Trials Group (ACTG) A5230.
abstract: BACKGROUND
  The AIDS Clinical Trials Group (ACTG) A5230 study evaluated lopinavir/ritonavir (LPV/r) monotherapy following virologic failure (VF) on first-line human immunodeficiency virus (HIV) regimens in Africa and Asia.
  
  
  METHODS
  Eligible subjects had received first-line regimens for at least 6 months and had plasma HIV-1 RNA levels 1000-200 000 copies/mL. All subjects received LPV/r 400/100 mg twice daily. VF was defined as failure to suppress to <400 copies/mL by week 24, or confirmed rebound to >400 copies/mL at or after week 16 following confirmed suppression. Subjects with VF added emtricitabine 200 mg/tenofovir 300 mg (FTC/TDF) once daily. The probability of continued HIV-1 RNA <400 copies/mL on LPV/r monotherapy through week 104 was estimated with a 95% confidence interval (CI); predictors of treatment success were evaluated with Cox proportional hazards models.
  
  
  RESULTS
  One hundred twenty-three subjects were enrolled. Four subjects died and 2 discontinued prematurely; 117 of 123 (95%) completed 104 weeks. Through week 104, 49 subjects met the primary endpoint; 47 had VF, and 2 intensified treatment without VF. Of the 47 subjects with VF, 41 (33%) intensified treatment, and 39 of 41 subsequently achieved levels <400 copies/mL. The probability of continued suppression <400 copies/mL over 104 weeks on LPV/r monotherapy was 60% (95% CI, 50%-68%); 80%-85% maintained levels <400 copies/mL with FTC/TDF intensification as needed. Ultrasensitive assays on specimens with HIV-1 RNA level <400 copies/mL at weeks 24, 48, and 104 revealed that 61%, 62%, and 65% were suppressed to <40 copies/mL, respectively.
  
  
  CONCLUSIONS
  LPV/r monotherapy after first-line VF with FTC/TDF intensification when needed provides durable suppression of HIV-1 RNA over 104 weeks.
  
  
  BACKGROUND
  NCT00357552.
authors.affiliation: YRG CARE Medical Centre, VHS Chennai, India.
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Aga
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.affiliation: Lancet Laboratories, Johannesburg, South Africa.
authors.forename: Carole L
authors.initials: CL
authors.lastname: Wallis
authors.affiliation: Stanford University, Palo Alto, California.
authors.forename: David A
authors.initials: DA
authors.lastname: Katzenstein
authors.affiliation: University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Stevens
authors.affiliation: AbbVie, North Chicago, Illinois.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Norton
authors.affiliation: Division of AIDS, National Institutes of Health, Bethesda, Maryland.
authors.forename: Karin L
authors.initials: KL
authors.lastname: Klingman
authors.affiliation: Kamuzu Central Hospital, Lilongwe, Malawi.
authors.forename: Mina C
authors.initials: MC
authors.lastname: Hosseinipour
authors.affiliation: Kilimanjaro Christian Medical Centre, Moshi, Tanzania.
authors.forename: John A
authors.initials: JA
authors.lastname: Crump
authors.affiliation: Chiang Mai University, Thailand.
authors.forename: Khuanchai
authors.initials: K
authors.lastname: Supparatpinyo
authors.affiliation: University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Sharlaa
authors.initials: S
authors.lastname: Badal-Faesen
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: John A
authors.initials: JA
authors.lastname: Bartlett
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D000349:Africa; D000998:Antiviral Agents / Q000627:therapeutic use*; D001208:Asia; D003906:Developing Countries; D004358:Drug Therapy / Q000379:methods; D005260:Female; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010949:Plasma / Q000821:virology; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D061466:Lopinavir; D019438:Ritonavir
keywords: ACTG 5230; intensification; protease inhibitor monotherapy; second-line antiretroviral therapy