A Randomized Comparison of Second-Line lopinavir/ritonavir Monotherapy Versus tenofovir/lamivudine/lopinavir/ritonavir in Patients Failing NNRTI Regimens: The HIV STAR Study

Antivir Ther. 2012;17(7):1351-61. doi: 10.3851/IMP2443. Epub 2012 Jul 2.

Abstract

Background: Data informing the use of boosted protease inhibitor (PI) monotherapy as second-line treatment are limited. There are also no randomized trials addressing treatment options after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-regimens.

Methods: HIV-infected subjects ≥18 years, with HIV RNA≥1,000 copies/ml while using NNRTI plus 2 NRTIs, and naive to PIs were randomized to lopinavir/ritonavir (LPV/r) 400/100 mg twice daily monotherapy (mono-LPV/r) or tenofovir disoproxil fumarate (TDF) once daily plus lamivudine (3TC) twice daily plus LPV/r 400/100 mg twice daily (TDF/3TC/LPV/r) at nine sites in Thailand. The primary outcome was time-weighted area under curve (TWAUC) change in HIV RNA over 48 weeks. The a priori hypothesis was that the mono-LPV/r arm would be considered non-inferior if the upper 95% confidence limit in TWAUC mean difference was ≤0.5 log(10) copies/ml.

Results: The intention-to-treat (ITT) population comprised 195 patients (mono-LPV/r n=98 and TDF/3TC/LPV/r n=97): male 58%, baseline mean (sd) age of 38 (7) years, CD4(+) T-cell count of 204 (135) cells/mm(3) and HIV RNA of 4.1 (0.6) log(10) copies/ml. The majority had HIV-1 recombinant CRF01_AE infection, and thymidine analogue mutation (TAM)-2 was 3× more common than TAM-1. At 48 weeks, the difference in TWAUC HIV RNA between arms was 0.15 (95% CI -0.04, 0.33) log(10) copies/ml, consistent with our definition of non-inferiority. However, the proportion with HIV RNA<50 copies/ml was significantly lower in the mono-LPV/r arm: 61% versus 83% (ITT, P<0.01). Baseline HIV RNA≥5 log(10) copies/ml (P<0.001) and mono-LPV/r use (P=0.003) were predictors of virological failure. Baseline genotypic sensitivity scores ≥2 and TAM-2 were associated with better virological control in subjects treated with the TDF-containing regimen.

Conclusions: In PI-naive patients failing NNRTI-based first-line HAART, mono-LPV/r had a significantly lower proportion of patients with HIV RNA<50 copies/ml compared to the TDF/3TC/LPV/r treatment. Thus, mono-LPV/r should not be recommended as a second-line option.

Trial registration: ClinicalTrials.gov NCT00627055.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Female
  • HIV / pathogenicity
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Lamivudine / therapeutic use*
  • Lopinavir / therapeutic use*
  • Male
  • Organophosphonates / therapeutic use*
  • Ritonavir / therapeutic use*
  • Tenofovir

Substances

  • HIV Protease Inhibitors
  • Organophosphonates
  • Lopinavir
  • Lamivudine
  • Tenofovir
  • Adenine
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT00627055