Once-Daily Atazanavir/Ritonavir Compared With Twice-Daily Lopinavir/Ritonavir, Each in Combination With Tenofovir and Emtricitabine, for Management of Antiretroviral-Naive HIV-1–Infected Patients: 96-Week Efficacy and Safety Results of the CASTLE Study

Molina, Jean‐Michel; Andrade-Villanueva, Jaime; Echevarría, Juan; Chetchotisakd, Ploenchan; Corral, Jorge; David, Neal; Moyle, Graeme; Mancini, Marco; Percival, Lisa; Yang, Rong; Wirtz, Victoria; Lataillade, Max; Absalon, Judith; McGrath, Donnie

doi:10.1097/qai.0b013e3181c990bf

Cited by 236 publications

(169 citation statements)

References 24 publications

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“…34,58 Similar to the results obtained here, safety results from ARTEMIS suggested low rates of grade 2-4 AEs, including gastrointestinal and renal AEs, in subjects receiving DRV/r over 96 weeks. 39 Subjects receiving DRV/r in ARTEMIS had a significantly lower rate of diarrhea compared with LPV/r subjects (4% vs. 11%, respectively) and, in line with results from this trial, no clinically relevant changes were seen in creatinine clearance in either treatment arm.…”

Section: Discussionsupporting

confidence: 74%

“…32,33 Another PI, atazanavir (ATV; REYATAZ, Bristol-Myers Squibb, Princeton, NJ), boosted with low-dose ritonavir (ATV/r), has also demonstrated a favorable metabolic profile in treatment-naive subjects. 34 The metabolic effects of DRV/r have been shown to be comparable with those of ATV/r in HIV-negative subjects. 33 Furthermore, the metabolic effects of these ARVs have not been directly compared in HIV-1-infected, treatmentnaive subjects.…”

Section: Introductionmentioning

confidence: 82%

“…1 Given that HIV infection is now considered a manageable chronic disease, there is a growing level of attention focused on the need for identification of metabolically favorable ARVs. Atazanavir has generally been considered to have the most favorable metabolic profile among PIs 34 and was, therefore, chosen as a comparator drug for this study. In the study presented here, changes in metabolic parameters and biomarkers from baseline with DRV/r were comparable to changes observed with ATV/r.…”

Section: Discussionmentioning

confidence: 99%

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Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Aberg

Tebas

Overton

et al. 2012

AIDS Research and Human Retroviruses

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We assessed metabolic changes for darunavir/ritonavir (DRV/r) once daily (qd) versus atazanavir/ritonavir (ATV/r) qd with fixed-dose tenofovir/emtricitabine. This was a phase 4, multicenter, open-label, randomized exploratory study. Treatment-naive, HIV-1-infected adults received DRV/r 800/100 mg qd or ATV/r 300/ 100 mg qd, both with emtricitabine/tenofovir 200/300 mg qd. Primary end point: change in triglyceride levels from baseline to week 12. Secondary end points: week 12 and week 48 changes in lipid parameters, insulin sensitivity, inflammatory/coagulation/bacterial translocation biomarkers, viral load, CD4 + cell count, and week 48 changes in adipose tissue distribution and subjects' perceptions of body changes. In the DRV/r arm, 32/34 and 29/34 subjects completed weeks 12 and 48, respectively; in the ATV/r arm, 30/31 and 25/31 subjects completed weeks 12 and 48, respectively. Small changes in lipid parameters from baseline to weeks 12 and 48 were observed in both arms. Differences were noted between arms in mean changes in total cholesterol (DRV/r, 20.3 mg/dl; ATV/r, 4.6 mg/dl) and apolipoprotein A1 (DRV/r, 10.7 mg/dl; ATV/r, -0.7 mg/dl) at week 12. At week 48, no clinically relevant differences between arms were noted for changes in any lipid parameter, fasting glucose, or insulin sensitivity. Biomarkers generally decreased and efficacy parameters improved in both arms over 48 weeks. Changes in adipose tissue were small and comparable between arms. Subjects' perceptions of body changes generally improved in both study arms. This first pilot comparison in HIV-1-infected subjects suggests that DRV/r has a metabolic profile similar to ATV/r over 48 weeks of treatment. Further randomized studies are warranted.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Aberg

Tebas

Overton

et al. 2012

AIDS Research and Human Retroviruses

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“…While adverse events were the main known reason for discontinuation, the long-term safety profile in this real-life study was consistent with that observed previously in clinical trials of up to 2 years duration, [5][6][7] with no new or unexpected adverse events identified.…”

Section: Jansen Et Alsupporting

confidence: 69%

“…Several PI agents are now available, providing options for individualized therapy, and most regimens are boosted with the pharmacological enhancer, ritonavir. 2 In clinical trials, convenient once-daily ritonavir-boosted atazanavir (ATV/r)-based regimens have proven efficacy and safety in both treatment-naive [3][4][5] and -experienced patients. 6,7 These regimens are recommended as a preferred therapeutic option for initiation of therapy in treatment-naive patients by the current treatment guidelines in both the United States 8,9 and Europe.…”

mentioning

confidence: 99%

Long-Term Efficacy and Safety of Atazanavir/Ritonavir Treatment in a Real-Life Cohort of Treatment-Experienced Patients with HIV Type 1 Infection

Jansen

Sönnerborg

Brockmeyer

et al. 2013

AIDS Research and Human Retroviruses

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Atazanavir-based regimens have established efficacy and safety in both antiretroviral (ARV)-naive and -experienced patients. However, data evaluating effectiveness beyond 2 years is sparse. Therefore, we assessed the long-term outcomes of ritonavir-boosted atazanavir (ATV/r)-containing regimens in ARV-experienced patients in a clinical setting in a noncomparative, retrospective, observational study collecting data from three European HIV databases on ARV-experienced adults with HIV-1 infection starting an ATV/r-based regimen. Data were extracted every 6 months (maximum follow-up 5 years). Primary outcome was the proportion of patients remaining on ATV/r by baseline HIV-1 RNA ( < 500 or ‡ 500 copies/ml). Secondary outcomes included time to virologic failure, reasons for discontinuation, and long-term safety profile. The duration of treatment and time to virologic failure were analyzed using the Kaplan-Meier method. Data were analyzed for 1,294 ARV-experienced patients (male 74%; mean ART exposure 5.7 years). After 3 years, 56% (95% CI: 52%, 60%) of patients with baseline HIV-1 RNA < 500 copies/ml and 53% (95% CI: 49%, 58%) of those with HIV-1 RNA ‡ 500 copies/ml remained on ATV/r. After 3 years, 75% (95% CI: 69%, 80%) of patients with baseline HIV-1 RNA < 50 copies/ml remained suppressed and 51% (95% CI: 47%, 55%) of those with baseline HIV-1 RNA ‡ 50 copies/ml achieved and maintained virologic suppression. Although adverse events (AEs) were the main known reason for discontinuation, no unexpected AEs were observed. In a real-life setting ATV/r-based regimens demonstrated sustained virologic suppression in ARV-experienced patients. After long-term therapy the majority of patients remained on treatment and no unexpected AEs were observed.

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Choice of Initial Combination Antiretroviral Therapy in Individuals With HIV Infection

et al. 2012

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BACKGROUND Current guidelines give recommendations for preferred combination antiretroviral therapy (cART). We investigated factors influencing the choice of initial cART in clinical practice and its outcome. METHODS We analyzed treatment-naive adults with human immunodeficiency virus (HIV) infection participating in the Swiss HIV Cohort Study and starting cART from January 1, 2005, through December 31, 2009. The primary end point was the choice of the initial antiretroviral regimen. Secondary end points were virologic suppression, the increase in CD4 cell counts from baseline, and treatment modification within 12 months after starting treatment. RESULTS A total of 1957 patients were analyzed. Tenofovir-emtricitabine (TDF-FTC)-efavirenz was the most frequently prescribed cART (29.9%), followed by TDF-FTC-lopinavir/r (16.9%), TDF-FTC-atazanavir/r (12.9%), zidovudine-lamivudine (ZDV-3TC)-lopinavir/r (12.8%), and abacavir/lamivudine (ABC-3TC)-efavirenz (5.7%). Differences in prescription were noted among different Swiss HIV Cohort Study sites (P < .001). In multivariate analysis, compared with TDF-FTC-efavirenz, starting TDF-FTC-lopinavir/r was associated with prior AIDS (relative risk ratio, 2.78; 95% CI, 1.78-4.35), HIV-RNA greater than 100 000 copies/mL (1.53; 1.07-2.18), and CD4 greater than 350 cells/μL (1.67; 1.04-2.70); TDF-FTC-atazanavir/r with a depressive disorder (1.77; 1.04-3.01), HIV-RNA greater than 100 000 copies/mL (1.54; 1.05-2.25), and an opiate substitution program (2.76; 1.09-7.00); and ZDV-3TC-lopinavir/r with female sex (3.89; 2.39-6.31) and CD4 cell counts greater than 350 cells/μL (4.50; 2.58-7.86). At 12 months, 1715 patients (87.6%) achieved viral load less than 50 copies/mL and CD4 cell counts increased by a median (interquartile range) of 173 (89-269) cells/μL. Virologic suppression was more likely with TDF-FTC-efavirenz, and CD4 increase was higher with ZDV-3TC-lopinavir/r. No differences in outcome were observed among Swiss HIV Cohort Study sites. CONCLUSIONS Large differences in prescription but not in outcome were observed among study sites. A trend toward individualized cART was noted suggesting that initial cART is significantly influenced by physician's preference and patient characteristics. Our study highlights the need for evidence-based data for determining the best initial regimen for different HIV-infected persons.

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Once-Daily Atazanavir/Ritonavir Compared With Twice-Daily Lopinavir/Ritonavir, Each in Combination With Tenofovir and Emtricitabine, for Management of Antiretroviral-Naive HIV-1–Infected Patients: 96-Week Efficacy and Safety Results of the CASTLE Study

Abstract: Noninferiority of atazanavir/ritonavir to lopinavir/ritonavir was confirmed at 96 weeks. Atazanavir/ritonavir had a better lipid profile and fewer gastrointestinal adverse events than lopinavir/ritonavir.

Cited by 236 publications

References 24 publications

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Long-Term Efficacy and Safety of Atazanavir/Ritonavir Treatment in a Real-Life Cohort of Treatment-Experienced Patients with HIV Type 1 Infection

Choice of Initial Combination Antiretroviral Therapy in Individuals With HIV Infection

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