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Session 80 Poster Abstracts
Antiretroviral Therapy: Predictors of Response and Virologic Failure
Monday, 1:30 - 3:30 pm
Poster Hall


548    
A Randomized Trial of 1 or 2 Protease Inhibitors in Combination with a Non-nucleoside Reverse Transcriptase Inhibitor and Background Therapy in Patients with Virologic Failure on an Initial Protease-inhibitor Containing Regimen
J Kostman*1, B Grund2, R Leduc2, J Baxter3,4, L Crane5, and Terry Beirn Community Programs for Clinical Research on AIDS
1Univ. of Pennsylvania Hlth. System, Philadelphia, USA; 2Univ. of Minnesota, Minneapolis, USA; 3Cooper Hosp.; 4Robert Wood Johnson Med. Sch., Camden, NJ, USA; and 5Wayne State Univ., Detroit, MI, USA

Background:  In CPCRA 057, investigators chose 1 of 2 treatment strategies, based on genotype and treatment experience, in patients (pts) with virologic failure on their first protease inhibitor (PI) containing regimen. This report describes the randomized comparison of 1 vs. 2 PIs in combination with a non-nucleoside reverse transcriptase inhibitor (NNRTI) and nucleoside reverse transcriptase inhibitors (NRTI).

Methods: Patients with plasma HIV RNA viral load >400 copies/mL on their first PI-containing regimen were randomized (1:1) to a regimen with either 1 PI, 1 NNRTI, and NRTI, or  2 PI, 1 NNRTI, and NRTI; open label. Eligible patients had been on their qualifying regimen for at least 16 weeks and had no NNRTI experience.  The PI in the failing regimen was either nelfinavir (NFV) (NFV group); or indinavir (IDV) or ritonavir (RTV) (I/R group).  The primary endpoint was the percentage of patients with viral load >10,000 copies/mL or death at month 12.

Results: </t>Between November 1998 and March 2000, 68 patients were enrolled by 15 CPCRA units, 38 patients in the NFV group and 30 patients the I/R group (27 IDV, 3 RTV); 28% were female, 51% African American, 31% white.  Mean baseline CD4 = 317 cells/mm3, mean log HIV RNA = 4.2 log copies/mL.  Major PI mutations were 30N (13/59), 46I/L (16/59), 90M (18/59), 82 A/F/T (10/59), and 84V (1/59). The prescribed 2 PI combinations included RTV/saquinavir (SQV) (400 mg/800 mg, 80%), RTV/IDV (400 mg/400 mg, 9%), SQV/NFV (1000 mg/1250 mg, 3%). Single PI were IDV (68%) or amprenavir (APV, 21%) in the NFV group, and NFV (93%) or APV (7%) in the I/R group. The prescribed NNRTI were efavirenz (88%) and nevirapine (12%). At 12 months, there were no deaths. Viral load and CD4 cell counts were available for 53 patients; 25% and 40% of the patients in the 2 PI and 1 PI groups, respectively, had a viral load >10,000 copies/mL (p = 0.27).  The viral load decreased by 1.4 log in the 2-PI group compared to 0.6 log in the 1-PI group (p = 0.05). CD4 cell counts increased by 69 in the 2-PI group compared to a decrease of 11 in the 1-PI group (p = 0.04). Subgroup analyses of the NFV and I/R grps showed the same trends within both groups, although differences were not statistically significant.

Conclusions: In patients with virologic failure on their first PI, the NNRTI-containing salvage regimens with 2 PI provided better virologic and immunologic responses than the regimens with 1 PI.

Keywords: Virologic Failure; Antiretroviral therapy; Drug Resistance