title: First-line antiretroviral therapy with nevirapine versus lopinavir-ritonavir based regimens in a resource-limited setting.
abstract: OBJECTIVE
  To compare WHO first-line antiretroviral therapy (ART) with nonnucleoside reverse transcriptase inhibitors (NNRTI)-based regimen with a boosted protease inhibitor (bPI) regimen in a resource-limited setting regarding treatment outcome and emergence of drug resistance mutations (DRMs).
  
  
  METHODS
  Treatment-naive adults were randomized to nevirapine (NVP) or ritonavir-boosted lopinavir (LPV/r) regimens each in combination with tenofovir (TDF)/emtricitabine (FTC) or zidovudine (ZDV)/lamivudine (3TC). Primary endpoint was the incidence of therapeutical (clinical and/or virologic) failure at week 48 with follow-up till week 96.
  
  
  RESULTS
  Four hundred and twenty-five patients (120 men; 305 women) received at least one dose of the study drug. mITT analysis showed no difference in proportion of therapeutical failure between treatment arms [67/209 (32%) in NVP vs. 63/216 (29%) LPV/r at week 48 (P = 0.53); 88/209 (42%) in NVP vs. 83/216 (38%) in LPV/r at week 96 (P = 0.49)]. Per-protocol analysis demonstrated significantly more virologic failure with NVP than with LPV/r regimens [at week 48: 19/167 (11%) vs. 7/166 (4%), P = 0.014; at week 96: 27/158 (17%) vs. 13/159 (8%), P =  0.019)]. Drug resistance mutations to NNRTI were detected in 19 out of 22 (86.3%) and dual-class resistance to nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI in 15 out of 27 (68.2%) of NVP failing patients. K65R mutation was present in seven out of 14 patients failing NVP-TDF/FTC regimen. No major protease inhibitor-DRM was detected among LPV/r failing patients. Discontinuation for adverse events was similar between treatment groups.
  
  
  CONCLUSIONS
  In resource-limited settings, first-line NNRTI-NRTI regimen as compared with bPI-based regimen provides similar outcome but is associated with a significantly higher number of virologic failure and resistance mutations in both classes that jeopardize future options for second-line therapy.
authors.affiliation: aSaint-Pierre University Hospital, 1000 Brussels, Belgium bLubumbashi Network & PNMLS, Bureau de Coordination PNMLS/Katanga, Avenue Likasi, Lubumbashi, Congo RDC cCHU Liège, 1 Avenue de l'Hôpital, Domaine Universitaire du Sart Tilman, Liège 1, Belgium.
authors.forename: Nathan
authors.initials: N
authors.lastname: Clumeck
authors.forename: Claude
authors.initials: C
authors.lastname: Mwamba
authors.forename: Kabamba
authors.initials: K
authors.lastname: Kabeya
authors.forename: Serge
authors.initials: S
authors.lastname: Matanda
authors.forename: Dolorès
authors.initials: D
authors.lastname: Vaira
authors.forename: Coca
authors.initials: C
authors.lastname: Necsoi
authors.forename: David
authors.initials: D
authors.lastname: Kadiebwe
authors.forename: Marc
authors.initials: M
authors.lastname: Delforge
authors.forename: Eric
authors.initials: E
authors.lastname: Kasamba
authors.forename: Chantal
authors.initials: C
authors.lastname: Milolo
authors.forename: Joe
authors.initials: J
authors.lastname: Ilunga
authors.forename: Liévin
authors.initials: L
authors.lastname: Kapend
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D018791:CD4 Lymphocyte Count; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D061466:Lopinavir / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage*; D063065:Organophosphonates / Q000008:administration & dosage; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage*; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir