Tipranavir/Ritonavir Is More Effective against Protease Inhibitor (PI)-resistant Strains than Other Ritonavir-boosted PIs

Protease inhibitor/ritonavir (PI/r)-based regimens are among the most potent anti-HIV combinations but it is unclear whether significant differences exist in potency between the distinct PI/r combinations in rescue interventions.

Patients with prior PI failure who initiated a regimen based on ritonavir 100 mg bid along with either SQV 1000 mg bid, IDV 800 mg bid, LPV 400 mg bid and APV 600 mg bid, or ATV/r 300/100 mg qd or TPV/r 500/200 mg bid, were retrospectively analyzed.

Results

A total of 389 patients were analyzed: SQV/r (139), IDV/r (35), LPV/r (129), APV/r (35), ATV/r (29) and TPV/r (22).

No significant differences in VL and CD4 at baseline were recognized between groups.

Virological Response (VR) (<50 copies/ml or >1 log reduction) in an ITT analysis at week 24 was 72.4% (ATV/r), 68.2% (TPV/r), 54.3% (LPV/r), 48.2% (SQV/r), 37.1% (IDV/r) and 28.6% (APV/r).

Median CD4 (cells/ml) increase was 63 (SQV/r), 63 (IDV/r), 57 (LPV/r), 48 (ATV/r), 17 (TPV/r) and 7 (APV/r).

Treatment discontinuation due to adverse events was higher using IDV/r (22.8%) with respect to others (p=0.03).

The total number of baseline protease resistance mutations (PRM) was associated with lower VR (OR=0.75; 95% CI=0.59-0.95; p=0.02).

Using the presence of <5 or >/=5 PRM at baseline to discriminate VR to therapy, the results were as follows: 100% vs. 64% (TPV/r), 75% vs. 47% (LPV/r), 77% vs. 46% (SQV/r), 93% vs. 33% (ATV/r), 89% vs. 25% (IDV/r), and 60% vs. 16% (APV/r).

APV/r was significantly less potent than other PI/r (p=0.04).

For individuals with >/=5 PRM, the response was significantly better for TPV/r compared to other PI/r (p=0.03).

The authors conclude, "PI/r-based regimens provide a significant rate of VR as salvage therapy. The main determinant of potency is the baseline protease resistance profile. While APV seems to be less potent, TPV/r demonstrated higher potency in patients with >/=5 PRM.

Hospital Carlos III, Infectious Diseases, Madrid, Spain, Hospital Vall d' Hebron, Barcelona, Spain.

08/18/06

Reference
C de Mendoza, E Ribera, P Barreiro, and others. Tipranavir/ritonavir is more effective against protease inhibitor (PI)-resistant strains than other ritonavir-boosted PI in heavily antiretroviral-experienced HIV-infected patients. 16th International AIDS Conference. August 13-18, 2006. Toronto, Canada. Abstract TUPE0205.