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24 Week RESIST Study Analysis: the efficacy of tipranavir/ritonavir is superior to lopinavir/r, and the TPV/r treatment response is enhanced by inclusion of genotypically active antiretrovirals in the optimized background regimen (OBR)
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Reported by Jules Levin
"......69.6% of patients naïve to T20 who included T20 along with TPV/r had a treatment response (1 log or more reduction in viral load)...." This compares to the overall percent of patients (39.6%) who received TPV/r who achieved a treatment response: if you never used T20 before & included it, treatment response rate increased by 75%
the 24 week treatment response increased with the use of more active background ARVs....each additional background ARV to which the patient was sensitive increased the response rates
In poster 560 David Cooper et al reported the following interesting data from the RESIST Study, the phase III study of tipranavir/ritonavir, the latest new treatment available for patients with extensive protease inhibitor resistance. Tipranavir is now available through an Expanded Access Program from the manufacturer, Boehringer Ingelheim, speak to your doctor about access. Approval by the FDA is in progress.
RESIST 1 & 2 are ongoing phase 3, multicenter, open-label trials in treatment-experienced patients randomized to a standard of care regimen containing either a boosted comparator PI (CPI/r) or TPV/r. The objectives of these analysis (poster 560) were to compare the efficacy of TPV/r & LPV/r, and to assess the role of additional active drugs to the OBR, particularly that of T-20.
Patients with 3 or more class ART experience, including 2 or more PI-based ARV regimens and 1 or more primary PI mutation, but 2 or less at amino acids 33, 82, 84, or 90 (TPV resistant mutations), and viral load >1000 copies/ml were eligible. Before randomization, an optimized CPI/r regimen (that could include T-20 in the OBR) was selected. Then patients received either TPV/r (500mg/200mg bid) or the preselected CPI/r (50% of investigators preselected LPV/r as optimized CPI/r) plus the OBR. The TPV/r and LPV/r treatment response was compared and the impact of active ARVs in the OBR was evaluated. Active drugs were defined as those with predicted ARV sensitivity based on interpretation of TruGene or VirtualPhenotype assays. Treatment response was defined as a confirmed 1 log or greater decrease in VL from baseline.
RESULTS
1483 patients were randomized & treated in the 2 trials; 1159 were available for analysis at 24 weeks. Median baseline values: VL, 4.8 log copies/ml; CD4 count, 162 cells; number of protease mutations, 16. Patients had previously received a median 12 prior ARVs. At 24 weeks, treatment response (ITT-NCF) was seen in 39.6% (116/293) and 21.4% (62/290) in the TPV/r and LPV/r groups, respectively (p<0.05); 34% & 18% respectively had VLs <400 copies/ml; 24% & 11% respectively had <50 copies/ml; and CD4 increase was +31 cells & +6 cells, respectively.
The 24-week treatment-response increased in both the TPV/r and CPI/r groups with the use of more active background ARVs: 0 active ARVs used (13.1% vs 9.1%, respectively), 1 (37.4% vs 12.9%), 2 (46.2% vs 19.9%, or 3 or more (54.7% vs 34.3%. A total of 24.7% OF PATIENTS USED T-20. AT WEEK 24, treatment response in patients using T-20 was: TPV/r arm, 58.2%, CPI/r arm, 25.8%. The treatment response in patients not using T-20 wasL TPV/r arm 34.9%; CPI/r arm, 16.9%.
AUTHOR CONCLUSIONS: The authors concluded that the 24 week RESIST study results indicate that TPV/r was superior to LPV/r across the multiple efficacy variables in these PI-experienced HIV+ patients. The TPV/r treatment response is enhanced when combined with additional active ARVs.
COMPARISON OF EFFICACY OF TPV/r & LPV/r
The poster reported responses to TPV/r & LPV/r in LPV/r naïve & experienced patients. In LPV/r naïve patients 45.3% receiving TPV/r & 36.1% receiving LPV/r had a VL reduction of 1 or more log copies/ml. Among LPV/r experienced patients, 35.2% receiving TPV/r & 10.7% receiving LPV/r (p<0.05) had a treatment response. Overall, 39.6% receiving TPV/r & 21.4% receiving LPV/r had a treatment response (p<0.0001).
Among patients who were LPV sensitive predicted by genotype: 45.7% receiving TPV/r & 39.6% receiving LPV/r had a treatment response. Among patients who were LPV resistant predicted by genotype, 35.8% receiving TPV/r & 13.1% receiving LPV/r had a treatment response.
RELATIONSHIP OF TREATMENT RESPONSE TO NUMBER OF GENOTYPICALLY ACTIVE ARVs
Genotypic sensitivity to 1, 2, or c3 or more background ARVs was associated with 0.24 log, 0.51 log, & o.74 log decreases in VL, respectively. See additional results above.
ADDITION OF T20 TO TREATMENT BACKGROUND OF TPV/r & LPV/r
27.1% of TPV/r patients & 22.2% of CPI/r patients used T20 as part of their treatment regimen. TPV/r & T20 use were associated with 0.64 log & 0.67 log decreases in VL, respectively.
WITH T20
69.6% of patients naïve to T20 who included T20 along with TPV/r had a treatment response. This compares to 30.6% of patients who were T20 experienced who included T20 along with TPV/r who had a treatment response. For patients in the CPI/r, 28.7% had treatment response if they used T20 & were naïve to it & 17.6% had treatment response if they were not T20 naïve & used it.
Without T20
For patients who did not use T20 & who were naïve to it 36.7% had a treatment response; for patients who were T20-experienced & did not use it they had 7.7% treatment response.
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