[9] THE INHIBITORY QUOTIENT (IQ) OF TIPRANAVIR/RITONAVIR (TPV/r) in TRIPLE CLASS EXPERIENCED HIV + PATIENTS; RESULTS FROM BI 1182.52.

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] THE INHIBITORY QUOTIENT (IQ) OF TIPRANAVIR/RITONAVIR (TPV/r) in TRIPLE CLASS EXPERIENCED HIV + PATIENTS; RESULTS FROM BI 1182.52.

[AUTHOR(S):] DL Mayers¹, VM Kohlbrenner¹, C Dohnanyi¹, JP Sabo¹, TR MacGregor¹, W Verbiest², P McKenna², S McCallister¹
¹Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT; ²Virco, Mechelen, Belgium

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 9
Antiviral Therapy 2003; 8(Suppl. 1):S187

[ABSTRACT:] Purpose: A high IQ-the ratio of trough plasma drug concentration to the protein-adjusted viral IC₅₀-is a useful indicator of the potential therapeutic margin of antiretroviral (AR) drugs. The IQ data for most AR drugs was obtained in studies of treatment naïve patients (pts). TPV is a non-peptidic protease inhibitor (NPPI) that has demonstrated sustained viral-load (VL) response during up to 80 weeks of treatment in multiple-protease inhibitor (PI)-experienced pts. The BI 1182.52 phase II study allowed evaluation of the IQ breakpoint for successful viral suppression using TPV in highly treatment experienced (HTE) pts.

Methods: : BI 1182.52 was an international, randomized, double-blinded trial of three doses (500 mg/100 mg; 500 mg/200 mg; and 750 mg/200 mg) of TPV/r given BID in HIV + pts. Pts were triple-class-experienced, and had detectable plasma virus on their > second PI-based regimen. IQ was calculated using the trough plasma TPV concentration at 14 days after starting TPV/r, divided by the protein-adjusted viral IC₅₀. The protein adjustment factor was 3.75. TPV IQ was related to the change in VL during two weeks of functional monotherapy with TPV/r in these HTE patients.

Results: 216 HIV + patients with a median baseline VL of 4.5 log₁₀ copies/mL and CD4+ cell counts of 153 cells/mm³ were enrolled. 157 pts from all 3 study arms were included in the IQ analysis. The median VL responses after 2 weeks of functional TPV/r monotherapy for IQs <5, >5-25, >25-50, >50-100, >100-150 and >150 were -0.19, -0.35, -0.82, -1.31, -0.96, and -1.23 respectively. This result suggests that there is an apparent IQ breakpoint of roughly 50 in HTE pts below which there is a decrease in antiviral response. 67% of patients in this study reached this IQ threshold >50.

Conclusions: The IQ of TPV observed in this trial of HTE triple class experienced pts compares favorably IQ data for other PIs obtained from treatment-naïve pts. This high IQ, coupled with the need for multiple protease gene mutations in most HIV isolates that show decreased susceptibility to TPV, suggests that TPV/r may provide antiviral activity in the majority of HTE HIV + patients.

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