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Estimated potency of six different boosted protease inhibitors regimens in antiretroviral-experienced HIV patients
- Impact of baseline protease resistance mutations
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5th European HIV Drug Resistance Workshop
Cascais, Portugal
March 30, 2007
Mark Mascolini
A retrospective survey of 422 people starting a salvage regimen based on a ritonavir-boosted protease inhibitor (PI) found no major 12-week response differences between the PIs studied, which included tipranavir but not darunavir [1]. The findings are at odds with results of the RESIST trials, which documented a better 48-week response to tipranavir/ritonavir than to other PIs [2]. Although a randomized trial like RESIST and a retrospective cohort analysis like this cannot readily be compared, the cohort study offers some insight into tipranavir use in the clinic
The study included all patients switching from a failing regimen to a boosted PI at three large Spanish HIV clinics. The researchers considered only people who remained on the same regimen for 24 weeks, so hard-to-tolerate regimens were not at a disadvantage in this analysis. The Spanish investigators defined virologic success as more than a 1-log (10-fold) drop in viral load or a load below 50 copies after 12 weeks of treatment.
The analysis involved 162 people starting lopinavir/ritonavir, 100 starting saquinavir/ritonavir, 59 starting atazanavir/ritonavir, 58 starting tipranavir/ritonavir, 35 starting (fos)amprenavir/ritonavir, and 8 starting indinavir/ritonavir.
People who began tipranavir had the highest median number of primary PI mutations (3, range 0 to 7), followed by saquinavir (1, range 0 to 5) and (fos)amprenavir (1, range 0 to 4). Median primary protease mutations measured 0 for the other PIs studied, so many patients in every group apparently switched to a boosted PI from a nonnucleoside or after taking a PI regimen that did not elicit detectable PI mutations.
Median length of PI exposure proved much higher in the tipranavir group (72 months) than with the other PIs (57 months for indinavir, 39 months for (fos)amprenavir, and 34 or fewer months for the other PIs). Median number of PI regimens already tried was 4.5 in the tipranavir group, 3 for (fos)amprenavir and indinavir, 2 for atazanavir and saquinavir, and 1 for lopinavir. Median number of active drugs besides PIs stood at 1 in the atazanavir group and 0 in all the other groups. Use of the fusion inhibitor enfuvirtide was limited almost exclusively to patients starting tipranavir.
All these baseline variables, plus baseline viral load and CD4 count, got factored into a multivariate analysis searching for predictors of virologic response. That analysis did not link any of the ritonavir-boosted PIs to a better or worse chance of virologic success. But three independent response predictors did emerge:
- Each additional primary PI mutation lowered the chance of virologic success about 30% (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.58 to 0.83, P < 0.001).
- Every previous PI lowered the chance about 40% (OR 0.61, 95% CI 0.49 to 0.76, P < 0.001).
- Using enfuvirtide hiked the chance of virologic success more than 10 times (OR 10.68, 95% CI 3.11 to 36.66, P < 0.001).
Thus in this large cohort of treatment-experienced people, using enfuvirtide had a huge impact on short-term response, but using tipranavir/ritonavir did not.
References
1. Ramirez-Olivencia G, Ribera E, Pena A, et al. Estimated potency of six different boosted protease inhibitors regimens in antiretroviral-experienced HIV patients: impact
of baseline protease resistance mutations. 5th European HIV Drug Resistance Workshop. March 28-30, 2007. Cascais, Portugal. Abstract 73.
2. Hicks CB, Cahn P, Cooper DA, et al. Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST) studies: an analysis of combined data from two randomised open-label trials. Lancet. 2006;368:466-475.
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