title: Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings.
abstract: OBJECTIVE
  To evaluate virologic response rates of lopinavir/ritonavir (LPV/r) monotherapy as second-line antiretroviral treatment (ART) among adults in resource-limited settings (RLSs).
  
  
  METHODS
  An open-label pilot study of LPV/r monotherapy in participants on first-line nonnucleoside reverse transcriptase inhibitor three-drug combination ART with plasma HIV-1 RNA 1000-200 000  copies/ml.
  
  
  METHODS
  Participants were recruited from five sites in Africa and Asia within the AIDS Clinical Trials Group (ACTG) network. All participants received LPV/r 400/100  mg twice daily. The primary endpoint was remaining on LPV/r monotherapy without virologic failure at week 24. Participants with virologic failure were offered addition of emtricitabine and tenofovir (FTC/TDF) to LPV/r.
  
  
  RESULTS
  Mutations associated with drug resistance were encountered in nearly all individuals screened for the study. One hundred and twenty-three participants were enrolled, and 122 completed 24 weeks on study. A high proportion remained on LPV/r monotherapy without virologic failure at 24 weeks (87%). Archived samples with HIV-1 RNA levels less than 400  copies/ml at week 24 (n=102) underwent ultrasensitive assay. Of these individuals, 62 had levels less than 40  copies/ml and 30 had levels 40-200  copies/ml. Fifteen individuals experienced virologic failure, among whom 11 had resistance assessed and two had emergent protease inhibitor mutations. Thirteen individuals with virologic failure added FTC/TDF and one individual added FTC/TDF without virologic failure. At study week 48, 11 of 14 adding FTC/TDF had HIV-1 RNA levels less than 400  copies/ml.
  
  
  CONCLUSIONS
  In this pilot study conducted in diverse RLS, LPV/r monotherapy as second-line ART demonstrated promising activity.
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA. jab5@duke.edu
authors.forename: John A
authors.initials: JA
authors.lastname: Bartlett
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.forename: Carole L
authors.initials: CL
authors.lastname: Wallis
authors.forename: Evgenia
authors.initials: E
authors.lastname: Aga
authors.forename: David A
authors.initials: DA
authors.lastname: Katzenstein
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Stevens
authors.forename: Michael R
authors.initials: MR
authors.lastname: Norton
authors.forename: Karin L
authors.initials: KL
authors.lastname: Klingman
authors.forename: Mina C
authors.initials: MC
authors.lastname: Hosseinipour
authors.forename: John A
authors.initials: JA
authors.lastname: Crump
authors.forename: Khuanchai
authors.initials: K
authors.lastname: Supparatpinyo
authors.forename: Sharlaa
authors.initials: S
authors.lastname: Badal-Faesen
authors.forename: Beatrice A
authors.initials: BA
authors.lastname: Kallungal
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000349:Africa / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D006295:Health Resources / Q000600:supply & distribution; D006801:Humans; D007194:India / Q000453:epidemiology; D061466:Lopinavir / Q000008:administration & dosage*; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage*; D018579:Patient Selection; D010865:Pilot Projects; D012367:RNA, Viral / Q000187:drug effects* / Q000276:immunology; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D019438:Ritonavir / Q000008:administration & dosage*; D011795:Surveys and Questionnaires; D000068698:Tenofovir; D013785:Thailand / Q000453:epidemiology; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D061466:Lopinavir; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir