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

AIDS. 2011 Nov 28;25(18):2269-78. doi: 10.1097/QAD.0b013e32834d0c20.

Abstract

Objectives: 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alkynes
  • Benzoxazines / pharmacology
  • Benzoxazines / therapeutic use
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV Protease Inhibitors / pharmacology*
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects*
  • Humans
  • Lopinavir / pharmacology
  • Lopinavir / therapeutic use
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • RNA, Viral / drug effects*
  • RNA, Viral / metabolism
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Ritonavir / pharmacology
  • Ritonavir / therapeutic use
  • Sex Factors
  • Treatment Outcome
  • Viral Load / drug effects

Substances

  • Alkynes
  • Benzoxazines
  • Cyclopropanes
  • HIV Protease Inhibitors
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Lopinavir
  • efavirenz
  • Ritonavir

Grants and funding