Home Search Abstracts Browse Sessions Program Committee View Session E-mail Abstract Author

 

 

Session 100 Poster Abstracts
Strategies of Antiretroviral Therapy
Friday, 1:30 - 3:30 pm
Hall A


577    
Randomized Study of Twice-daily Lopinavir/ritonavir or Fosamprenavir + Ritonavir vs Lopinavir/ritonavir + Fosamprenavir (with Tenofovir DF and Nucleosides) as Rescue Therapy
Ann Collier*1, C Tierney2, G Downey2, S Eshleman3, A Kashuba4, K Klingman5, E Vergis6, G Pakes7, J Rooney8, A Rinehart9, J Mellors6, and for the Adult AIDS Clinical Trials Group Protocol 5143 Team
1Univ of Washington, Seattle, USA; 2Harvard Sch of Publ Hlth, Boston, MA, USA; 3Johns Hopkins Univ, Baltimore, MD, USA; 4Univ of North Carolina at Chapel Hill, USA; 5NIH, DHHS, Bethesda, MD, USA; 6Univ of Pittsburgh, PA, USA; 7GlaxoSmithKline, Research Triangle Park, NC, USA; 8Gilead Sci, Foster City, CA, USA; and 9Virco Lab, Inc, Durham, NC, USA

Background:  Better therapies are needed for patients failing antiretroviral treatment. This study tested whether lopinavir (LPV) 400 mg/ritonavir (r) 100 mg + fosamprenavir (FPV) 700 mg twice daily (double protease inhibitor [PI]) leads to superior HIV-1 RNA response compared with LPV/r or FPV + r (single PI) in persons with virologic failure to protease inhibitor-based therapy.

Methods:  This was an open-label, multicenter, selectively randomized study in which subjects were randomized based on prior LPV/r, amprenavir (APV), or FPV experience; all received at least 1 new PI. The PI were given with TDF and 1 or 2 NRTI chosen using a virtual phenotype. Analyses compared the combined single PI arms to the double PI arm in intent-to-treat (ITT) and as-treated (AT) analyses stratified by prior LPV/r and APV or FPV experience. Virologic response was defined as > 1 log10 copies/mL decline from baseline or having < 50 copies/mL at week 24.

Results:  Baseline characteristics and NRTI use were similar between groups. Median entry CD4+ cells and HIV-1 RNA were 188/mm3 and 4.5 log10 copies/mL. When a pharmacokinetic sub-study interim analysis showed that LPV and APV exposures were significantly lower in the double PI arm than in the single PI arms (p < 0.0008 and < 0.0001, respectively), enrollment was stopped early at 56 of a planned 216 subjects, follow-up was shortened from 48 to 24 weeks, and subjects on the double PI arm had to stop LPV/r or FPV. Week 24 virologic responses were 75% with double (n = 28) and 61% with single (n = 28) PI (ITT, p = 0.17); and 100% with double (n = 12) and 64% with single (n = 25) PI (AT, p = 0.02). At week 24, HIV-1 RNA was < 50 copies/mL in 54% and 46% of double and single PI subjects (ITT, p = 0.37), and 75% and 48% (AT, p = 0.14), respectively. In the 26 subjects with virologic failure, 5 subjects taking double PI and 10 taking single PI developed ≥ 1 new resistance mutation. CD4+ cells increased a median of 81 and 41/mm3 (ITT, p = 0.4) and 114 and 43 /mm3 (AT, p = 0.08) in double and single PI groups, respectively. Clinical events and toxicity rates were similar among groups.

Conclusions:  The comparison between double and single PI groups was limited by early termination of enrollment and the resulting small sample size. RNA and CD4+ cell responses did not differ significantly between groups in the ITT analyses and trends favored the double PI group in the AT analyses, although this should be interpreted cautiously. Reduction of drug exposure to LPV and FPV in the double PI arm did not adversely affect virologic responses.

Keywords: antiretroviral therapy; protease inhibitors; HIV resistance