Efficacy and Safety of Atazanavir-Based Highly Active Antiretroviral Therapy in Patients with Virologic Suppression Switched from a Stable, Boosted or Unboosted Protease Inhibitor Treatment Regimen: The SWAN Study (AI424-097) 48-Week Results

The University of Edinburgh, Edinburgh, Scotland, United Kingdom
Clinical Infectious Diseases (Impact Factor: 8.89). 07/2007; 44(11):1484-92. DOI: 10.1086/517497
Source: PubMed


Atazanavir is a once-daily protease inhibitor (PI) for the treatment of human immunodeficiency virus (HIV) infection that has previously been studied in cohorts of treatment-naive and treatment-experienced patients. Limited data are available on the usefulness of switching from a PI-based regimen to a regimen based on a different PI, such as atazanavir, in HIV-infected patients experiencing virologic suppression but seeking regimen simplification.
The Switch to Another Protease Inhibitor (SWAN) study was a 48-week, open-label trial involving HIV-positive patients with virologic suppression who were receiving stable PI-based regimens (with or without ritonavir). Patients were randomized 2 : 1 to switch to atazanavir (400 mg per day)--or, if they were receiving tenofovir, to atazanavir-ritonavir (300/100 mg per day)--or to continue to receive their existing PI. The proportion of patients who experienced virologic rebound (defined as an HIV RNA load >or=50 copies/mL) was compared through study week 48.
Patients either received an atazanavir-containing regimen (278 patients) or continued to receive a comparator PI-containing regimen (141 patients). The proportion of patients who experienced virologic rebound was significantly lower among those who switched to an atazanavir-containing regimen (19 [7%] of 278) than it was among those who continued to receive a comparator PI regimen (22 [16%] of 141; P=.004). Patients who switched to atazanavir therapy experienced significantly fewer total cholesterol, fasting triglyceride, and non-high density lipoprotein cholesterol elevations than did patients in the comparator PI group (P<.001); patients receiving atazanavir had comparable rates of adverse event-related discontinuation and serious adverse events.
In patients with virologic suppression who were receiving other PIs, switching to a once-per-day regimen containing atazanavir provided better maintenance of virologic suppression (as demonstrated by significantly lower rates of virologic rebound and treatment failure than those observed with continued unmodified therapy), a comparable safety profile, and improved lipid parameters, compared with those for patients who continued their prior PI-based regimen through 48 weeks.

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    • "A number of advancements have been made to ART in the past decade. For example, the introduction of TDF has provided another safe and efficacious alternative to d4T [16], [17]; the availability of once-daily EFV has provided a more convenient alternative to twice daily NVP that induces less NNRTI resistance [18]; and the development of boosted PIs has allowed smaller, less frequent PI doses that offer improved safety, convenience and efficacy.[19]–[21] Additionally, improvements in general HIV care have been strongly encouraged, particularly in resource-limited settings. "
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    ABSTRACT: Background Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes. Methods Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥6 months were included. Predictors of treatment failure and treatment modification were assessed. Results Data from 4662 eligible patients was analysed. Patients started ART in 2003–2006 (n = 1419), 2007–2010 (n = 2690) and 2011–2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7–23.5] events per 100 patient/years in 2003–2006, 15.8 [14.9–16.8] in 2007–2010, and 11.6 [9.4–14.2] in 2011–2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33–0.81], p = 0.004 for 2011–2013 versus 2003–2006), older age (1.56 [1.19–2.04], p = 0.001 for ≥50 years versus <30years), female sex (1.29 [1.11–1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06–1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28–20.54], p<0.001 for stavudine-based regimens versus tenofovir-based). Conclusions The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure.
    Full-text · Article · Sep 2014 · PLoS ONE
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    • "However, a pharmacological interaction occurs during co-administration of ATV and TDF, which has resulted in recommendations to continue low-dose ritonavir (RTV), which might reduce the expected benefit [1], [2], [8]. With this background, not one of the randomized studies demonstrating the non-inferiority of a maintenance strategy with ATV0-based triple therapy was conducted in patients receiving TDF [3], [4], [9]. Recently, two cohort studies have demonstrated the durability and safety of maintenance with ATV0-based triple therapy co-administered with TDF, but none included direct comparison with a RTV-boosted ATV regimen (ATV/r) [10], [11]. "
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    ABSTRACT: Background Among HIV-1 infected patients who achieved virologic suppression, the use of atazanavir without pharmacologic boosting is debated. We evaluated the efficacy and tolerance of maintenance therapy with unboosted atazanavir in clinical practice. Methods and Results This multicenter retrospective cohort study evaluated the efficacy of switching HIV-1-infected patients controlled on triple therapy to unboosted (ATV0, n = 98) versus ritonavir-boosted atazanavir (ATV/r, n = 254) +2 nucleos(t)ide reverse transcriptase inhibitors. The primary endpoint was time to virologic failure (VF, >200 copies/mL). ATV groups were compared controlling for potential confounding bias by inverse probability weighted Cox analysis and propensity-score matching. Overall and adjusted VF rates were similar for both strategies. Both strategies improved dyslipidemia and creatininemia, with less jaundice in the ATV0 group. Conclusion In previously well-suppressed patients, within an observational cohort setting, ATV0–based triple-therapy appeared as effective as ATV/r- based triple-therapy to maintain virologic suppression, even if co-administered with TDF, but was better tolerated.
    Full-text · Article · Nov 2012 · PLoS ONE
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    • "Several newer PIs show fewer metabolic side effects than have been observed for ritonavir-boosted lopinavir (LPV/r) or ritonavir (RTV) in therapeutic dosage [24,32-35,38-41]. Especially atazanavir (ATV) so far has shown a relatively favourable lipid profile [42-45]. Saquinavir (SQV) as well has been observed to have few negative effects on the serum lipids [46-49]. "
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    ABSTRACT: One focus in the medical care of HIV-infected patients today is cardiovascular risk reduction. Metabolic disturbances occur frequently in patients taking protease inhibitors (PI) and are a major risk factor for atherosclerosis. With few published head-to-head studies substance-specific differences concerning metabolic effects are insufficiently defined. Therefore this cohort study directly compared the metabolic profiles of boosted atazanavir (ATV/r), fosamprenavir (FPV/r) and saquinavir (SQV/r). Data from a cohort of 124 HIV patients initiating a boosted regimen with one of the PIs at the University of Munich (LMU) infectious diseases outpatient clinic were retrospectively analyzed. The main outcome measures were median absolute total cholesterol levels and median relative change of total cholesterol levels after six months of PI-therapy. A multivariate linear regression model was built to identify and control for potential confounders of the association between PI-therapy and serum cholesterol level. 84 patients were treated with ATV/r, 23 patients received FPV/r and 17 patients SQV/r. Demographically the cohort constituted a representative sample of HIV-infected patients in Germany. There were no statistically significant differences between the comparison groups at baseline. - After six months of therapy median serum cholesterol in the ATV/r group dropped significantly from 204 mg/dl to 186 mg/dl, while in the FPV/r and SQV/r groups a rise in serum cholesterol levels was observed from 179 mg/dl to 204 mg/dl and from 173 mg/dl to 209 mg/dl respectively. The multivariate linear regression model identified a significant interaction between BMI at baseline and treatment with FPV/r: patients with higher BMI showed more prominent increases in serum cholesterol while taking FPV/r compared to patients with lower BMI. This cohort study demonstrated the most favourable impact on serum cholesterol levels and thus cardiovascular risk for ATV/r compared to FPV/r and SQV/r under real-life conditions. Given the statistical interaction detected between FPV/r and BMI further studies assessing metabolic profiles of different antiretroviral drugs in specific patient populations are urgently needed.
    Preview · Article · Feb 2011 · European journal of medical research
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