Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: The SPIRAL study

Infectious Diseases Unit, Hospital Clínic-Institut d'Investigaciones Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
AIDS (London, England) (Impact Factor: 5.55). 05/2010; 24(11):1697-707. DOI: 10.1097/QAD.0b013e32833a608a
Source: PubMed


Switching to raltegravir in selected patients treated with ritonavir-boosted protease inhibitors may result in similar efficacy and lower plasma lipids.
SPIRAL is a 48-week multicentre, open-label trial in which HIV-infected adults with less than 50 copies/ml of plasma HIV RNA for at least the previous 6 months on ritonavir-boosted protease inhibitor-based therapy were randomized (1: 1) to switch from the ritonavir-boosted protease inhibitor to raltegravir or to continue on ritonavir-boosted protease inhibitor-based therapy. Primary endpoint was the proportion of patients free of treatment failure (noncompleter = failure) at 48 weeks. SPIRAL study was powered to show noninferior efficacy of raltegravir-based therapy with a margin of -12.5%.
Two hundred and seventy-three patients assigned to switch to raltegravir (n = 139) or to continue ritonavir-boosted protease inhibitor (n = 134) were included in the efficacy analysis. At 48 weeks, 89.2% (raltegravir-based therapy) and 86.6% (ritonavir-boosted protease inhibitor-based therapy) of the patients remained free of treatment failure [difference 2.6%; 95% confidence interval (CI) -5.2 to 10.6]. A total of 96.9% (raltegravir-based therapy) and 95.1% (ritonavir-boosted protease inhibitor-based therapy) of the patients remained free of virological failure (difference 1.8%; 95% CI -3.5 to 7.5). Switching to raltegravir was associated with significant decreases in plasma lipids and total-to-HDL cholesterol ratio relative to continuing ritonavir-boosted protease inhibitor. Severe adverse events and study drug discontinuations due to any adverse event occurred in 4 and 2% of the patients in each group.
In patients with sustained virological suppression on ritonavir-boosted protease inhibitor-based therapy, switching from ritonavir-boosted protease inhibitor to raltegravir demonstrated noninferior efficacy and resulted in a better lipid profile at 48 weeks than continuing ritonavir-boosted protease inhibitor.

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    • "Two studies have reported outcomes at 48 weeks.45,46,48 One study examined RAL substituted for enfuvirtide, and the second study looked at using RAL in place of a ritonavir-boosted PI.45,46,48 The EASIER ARNS 138 trial was an open-label, randomized study looking at patients with 3-class drug failure or intolerance on enfuvirtide-based regimens with viral loads <400 copies/mL for >3 months.45,48 "
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    • "Proportion of patients with plasma HIV - 1 RNA , 50 copies / ml at week 48 in the absence of treatment modification . Martinez / 2010 / SPIRAL [ 43 ] Government ; "
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