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

Abstract

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.

Inflammatory Biomarker Changes and Their Correlation with Framingham Cardiovascular Risk and Lipid Changes in Antiretroviral-Naive HIV-Infected Patients Treated for 144 Weeks with Abacavir/Lamivudine/Atazanavir with or without Ritonavir in ARIES

“…40,41 Despite the elevations in these particular lipids for subjects receiving the ritonavir-boosted regimen, it should be noted that median values for the ATV/r-treated subjects remained below NCEP cutoffs for use of lipidlowering agents. Among the ritonavir-boosted protease inhibitors, ATV/r has low lipogenicity, as evidenced by fewer lipid increases than lopinavir/r and only small lipid elevations reported in direct comparisons in treatment-naive subjects 14,42 and in treatment-experienced subjects switched from lopinavir/r to ATV/r. 43,44 Unboosted ATV, relative to most other protease inhibitors, has been documented to have little effect on lipids, 45 which is consistent with what we observed.…”

MECHANISMS IN ENDOCRINOLOGY: Metabolic and body composition effects of newer antiretrovirals in HIV-infected patients

“…In addition, fibrinogen, D-dimer, TNF RII, and LPS decreased in both darunavir and atazanavir groups at 48 weeks, but only TNF RII was significantly lower in the darunavir/ritonavir group. There were small increases in hsCRP and IL6 in both treatment arms (88). After ART-experienced HIV-infected patients on triple ART were switched to darunavir/ritonavir monotherapy vs darunavir with two NRTIs, there was a decrease in FMD at 48 weeks, but the changes were not statistically significantly different between groups (91).…”

Prevalence of insulin resistance and risk of diabetes mellitus in HIV-infected patients receiving current antiretroviral drugs

“…Efavirenz, nevirapine, raltegravir, tenofovir, abacavir, and lamivudine have been associated with lower risk of mitochondrial toxicity, and low DM risk (44,45,46). In addition, newer PI, especially atazanavir and darunavir, have been shown to have lower metabolic toxicity and to rarely cause IR (47,48,49,50,51), a fact that could even explain the improvement of IR in pretreated patients switching to these drugs, as previously described with atazanavir, efavirenz, or nevirapine (47,52). However, the cross-sectional inclusion of our patients precludes us to know whether lower IR found in pretreated patients is due to persistence of this complication or is the result of progressive decrease with the use of new drugs with a lower toxicity.…”