title: Initial viral decay to assess the relative antiretroviral potency of protease inhibitor-sparing, nonnucleoside reverse transcriptase inhibitor-sparing, and nucleoside reverse transcriptase inhibitor-sparing regimens for first-line therapy of HIV infection.
abstract: OBJECTIVE
  To evaluate the effects of sex and initial antiretroviral regimen on decay of HIV-RNA and virologic outcome.
  
  
  METHODS
  We conducted a viral dynamics substudy of A5142, a trial comparing lopinavir (LPV)/ritonavir with efavirenz (LPV/EFV) versus LPV and two nucleoside reverse transcriptase inhibitor (NRTI) (LPV) versus EFV and two NRTI (EFV) in antiretroviral (ARV)-naive individuals. HIV-RNA was measured at days 2, 10, and 14 in the substudy and at weeks 1, 4, and 8 in A5142 participants. Two-phase viral decay was estimated in the substudy with biexponential mixed-effects modeling and compared using Wilcoxon tests. Week 1 HIV-RNA change was assessed as a predictor of virologic failure (HIV-RNA above 50 or 200  copies/ml) at weeks 24-96 using logistic regression.
  
  
  RESULTS
  Sixty-eight individuals were enrolled in the substudy (median HIV-RNA 4.9 log(10)  copies/ml). Median rates of phase 1 viral decay by treatment were 0.61(EFV/LPV), 0.53(LPV), and 0.63(EFV) per day. Phase 1 decay was significantly faster for EFV than LPV (P = 0.023); other comparisons were not significant (P > 0.11). Viral decay did not differ by sex (P = 0.10). Week 1 HIV-RNA change, calculated in 571 participants of A5142, was greater for the EFV (median -1.47 log(10)  copies/ml) than either the LPV/EFV or LPV groups (-1.21 and -1.16 log(10 ) copies/ml, respectively; P < 0.001). Week 1 HIV-RNA change was associated with virologic failure above 50  copies/ ml at weeks 24 and 48 (P < 0.018), but not above 200  copies/ml at these time points or for any value at week 96.
  
  
  CONCLUSIONS
  Phase 1 decay was faster for EFV than LPV or LPV/EFV. Week 1 HIV-RNA change predicted virologic outcome up to week 48, but not at week 96.
authors.affiliation: Antiviral Research Center, University of California San Diego, San Diego, California 92103, USA. rhaubrich@ucsd.edu
authors.forename: Richard H
authors.initials: RH
authors.lastname: Haubrich
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Riddler
authors.forename: Heather
authors.initials: H
authors.lastname: Ribaudo
authors.forename: Gregory
authors.initials: G
authors.lastname: Direnzo
authors.forename: Karin L
authors.initials: KL
authors.lastname: Klingman
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Garren
authors.forename: David L
authors.initials: DL
authors.lastname: Butcher
authors.forename: James F
authors.initials: JF
authors.lastname: Rooney
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
mesh_terms: D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000494:pharmacology / Q000627:therapeutic use; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D061466:Lopinavir / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use; D012737:Sex Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; C098320:efavirenz; D019438:Ritonavir