Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: The SPIRAL study
ABSTRACT 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.
Full-textDOI: · Available from: Josep M Llibre, Aug 12, 2015
- SourceAvailable from: Vinay Pasupuleti
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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 ; "
ABSTRACT: Non-inferiority (NI) randomized clinical trials (RCTs) commonly evaluate efficacy of new antiretroviral (ARV) drugs in human immunodeficiency virus (HIV) patients. Their reporting and interpretation have not been systematically evaluated. We evaluated the reporting of NI RCTs in HIV patients according to the CONSORT statement and assessed the degree of misinterpretation of RCTs when NI was inconclusive or not established. Systematic review. PubMed, Web of Science, and Scopus were reviewed until December 2011. Selection and extraction was performed independently by three reviewers. Of the 42 RCTs (n = 21,919; range 41-3,316) selected, 23 were in ARV-naïve and 19 in ARV-experienced patients. Twenty-seven (64%) RCTs provided information about prior RCTs of the active comparator, and 37 (88%) used 2-sided CIs. Two thirds of trials used a NI margin between 10 and 12%, although only 12 explained the method to determine it. Blinding was used in 9 studies only. The main conclusion was based on both intention-to-treat (ITT) and per protocol (PP) analyses in 5 trials, on PP analysis only in 4 studies, and on ITT only in 31 studies. Eleven of 16 studies with NI inconclusive or not established highlighted NI or equivalence, and distracted readers with positive secondary results. There is poor reporting and interpretation of NI RCTs performed in HIV patients. Maximizing the reporting of the method of NI margin determination, use of blinding and both ITT and PP analyses, and interpreting negative NI according to actual primary findings will improve the understanding of results and their translation into clinical practice.PLoS ONE 05/2013; 8(5):e63272. DOI:10.1371/journal.pone.0063272 · 3.53 Impact Factor
HIV and AIDS - Updates on Biology, Immunology, Epidemiology and Treatment Strategies, 10/2011; , ISBN: 978-953-307-665-2
- ") showed that patients randomized to LPV/r or FPV/r presented greater elevations of total cholesterol and triglycerides than those assigned to SQV/r, ATV/r, or DRV/r, without differences in low density lipoprotein cholesterol (LDL) or HDL. The integrase inhibitor RAL is the first drug in this class and shows a remarkable lack of relevant adverse effects (Emery et al., 2010) and patients treated with RAL presented a significantly low frequency of dyslipidemia (Martinez et al., 2010). Trials with HIV-1 patients treated with chemokine receptor-5 antagonist MVC have shown that it has a very favorable safety profile. "
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ABSTRACT: Les traitements antirétroviraux ont considérablement amélioré le pronostic de l’infection par le virus de l’immunodéficience humaine (VIH) et sont largement prescrits en France chez les patients suivis pour cette infection. L’admission fréquente des patients infectés par le VIH en réanimation confronte régulièrement le réanimateur à la gestion de ces médicaments, à côté des autres traitements de réanimation. Cette revue aborde les principes généraux du traitement antirétroviral dans l’infection par le VIH, puis plus spécifiquement des conditions d’utilisation des médicaments antirétroviraux en réanimation, incluant leurs circonstances d’utilisation, leurs modalités d’administration, leur toxicité et leurs interactions médicamenteuses potentielles. Antiretroviral drugs have dramatically improved the prognosis of human immunodeficiency virus (HIV) infection over the recent decades. Currently, most of the HIV-infected patients in France are receiving antiretroviral therapy. Since admission of HIV-infected patients to the intensive care unit (ICU) is not an infrequent event, ICU physicians may commonly have to manage antiretroviral drugs besides the regular intensive care medications. This review focuses on the general principles of antiretroviral therapy in HIV infection as well as on some important points related to the specific use of antiretroviral agents in the ICU, including optimal starting time, administration regimen, drug toxicities, and drug-drug interactions. Mots clésAntirétroviraux–VIH–Réanimation–Thérapeutique–Interaction médicamenteuse–Toxicité médicamenteuse KeywordsAntiretroviral therapy–HIV–Intensive care–Therapeutics–Drug-drug interaction–Drug toxicityRéanimation 05/2011; 20(3):234-241. DOI:10.1007/s13546-011-0254-y