The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults

Noor, Mustafa A.; Parker, Rex A.; O’Mara, Edward; Grasela, Dennis M.; Currie, Alexander; Hodder, Sally; Fiedorek, Fred T.; Haas, David W.

doi:10.1097/00002030-200411050-00005

Cited by 181 publications

(148 citation statements)

References 15 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

Section: Discussioncontrasting

confidence: 92%

“…In contrast to some other PIs, 8,10,11 no clinically significant changes were seen in insulin sensitivity in either the DRV/r or ATV/r arm of this study. Treatment with indinavir and treatment with LPV/r have both been associated with the development of insulin resistance in healthy subjects [9][10][11] ; however, other studies have demonstrated that LPV/r does not affect insulin sensitivity in healthy subjects. 12,13 Atazanavir has generally had little effect on insulin sensitivity in previous trials of HIV-negative subjects, 10,12 and switching from other PI-based therapies to ATV/r has been shown to improve insulin sensitivity in HIV-1-infected subjects.…”

Section: Discussioncontrasting

confidence: 92%

“…Treatment with indinavir and treatment with LPV/r have both been associated with the development of insulin resistance in healthy subjects [9][10][11] ; however, other studies have demonstrated that LPV/r does not affect insulin sensitivity in healthy subjects. 12,13 Atazanavir has generally had little effect on insulin sensitivity in previous trials of HIV-negative subjects, 10,12 and switching from other PI-based therapies to ATV/r has been shown to improve insulin sensitivity in HIV-1-infected subjects. 54 The results from this trial suggest that DRV/r, likewise, has little impact on insulin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6][7] Additionally, some PIs have been associated with insulin resistance in HIV-negative healthy volunteers. [8][9][10][11] However, this association with insulin resistance seems to be ARV-specific, as opposed to class-specific, as studies evaluating other PIs have failed to demonstrate such an association. 12,13 The metabolic complications associated with PI-based therapy can develop within the first week after treatment initiation.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussioncontrasting

confidence: 92%

Section: Discussioncontrasting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

show abstract

“…12 In HIV, the HS etiology is most likely multifactorial 13 relating to metabolic factors, e.g., insulin resistance/DM/dyslipidemia and lipodystrophy, all of which may be linked to antiretroviral therapy (ART). Protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors (NRTI) have been related to insulin resistance 14 and lipodystrophy 15 ; NRTI may cause mitochondrial dysfunction with subsequent direct hepatotoxic effects. 16 Moreover, HIV infection itself may facilitate DM by way of tumor necrosis factor-a stimulation and mitochondria damage.…”

mentioning

confidence: 99%

Hepatic steatosis in patients coinfected with human immunodeficiency virus/hepatitis C virus: A meta-analysis of the risk factors

2010

View full text Add to dashboard Cite

Hepatic steatosis (HS) is frequent in patients with hepatitis C virus (HCV) infection, occurring in 40%-80%, associating with metabolic and virus-related factors, namely, genotype 3 and viral load. Human immunodeficiency virus (HIV) infection and antiretroviral treatment seem to be risk factors for HS. Several studies addressed this issue in coinfected patients, with discrepant results. A meta-analysis was performed on the HS risk factors in coinfected patients. Eligible studies were identified through structured keywords including coinfection, HCV, HIV, and steatosis in relevant databases including PubMed. Pooled odds ratios (ORs) and confidence limits (CIs) were obtained with the random-effects model and the DerSimonian-Laird method. Twelve studies, including 1,989 coinfected patients, were selected. Twenty percent were infected with HCV genotype 3. The overall prevalence of HS was 50.8% (23%-72%). Four studies also included 1,540 HCV monoinfected patients, not showing an increased risk for HS in coinfected patients (OR 1.61, 95% CI 0.84-3.10, P 5 0.151). In coinfected patients, HS was associated with higher body mass index (OR 1.13, 95% CI 1.07-1.19, P < 0.001), diabetes mellitus (OR 2.32, 95% CI 1.32-4.07, P 5 0.003), elevated alanine aminotransferase levels (OR 1.28, 95% CI 1.02-1.61, P 5 0.035), necroinflammatory activity (OR 1.72, 95% CI 1.11-2.67, P 5 0.016), and fibrosis (OR 1.67, 95% CI 1.20-2.34, P 5 0.003). No associations were found between HS and gender, other metabolic factors (dyslipidemia, glucose, metabolic syndrome), HCV-related factors (genotype, viral load), or HIV-related factors (viral load, CD4 count, antiretroviral therapy, and class of medication). Conclusion: In coinfected patients, HS does not seem to be more frequent than in HCV monoinfected patients and is mostly associated with metabolic factors, such as increased weight, diabetes mellitus, and more severe liver disease. The fact that no associations with HCV factors were found may be due to the small percentage of genotype 3-infected patients. (HEPATOLOGY 2010;52:71-78)

show abstract

Proteases and protease inhibitors in infectious diseases

Agbowuro

Huston

Gamble

et al. 2017

Medicinal Research Reviews

168

103

View full text Add to dashboard Cite

There are numerous proteases of pathogenic organisms that are currently targeted for therapeutic intervention along with many that are seen as potential drug targets. This review discusses the chemical and biological makeup of some key druggable proteases expressed by the five major classes of disease causing agents, namely bacteria, viruses, fungi, eukaryotes, and prions. While a few of these enzymes including HIV protease and HCV NS3-4A protease have been targeted to a clinically useful level, a number are yet to yield any clinical outcomes in terms of antimicrobial therapy. A significant aspect of this review discusses the chemical and pharmacological characteristics of inhibitors of the various proteases discussed. A total of 25 inhibitors have been considered potent and safe enough to be trialed in humans and are at different levels of clinical application. We assess the mechanism of action and clinical performance of the protease inhibitors against infectious agents with their developmental strategies and look to the next frontiers in the use of protease inhibitors as anti-infective agents.

show abstract

The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults

Cited by 181 publications

References 15 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

Hepatic steatosis in patients coinfected with human immunodeficiency virus/hepatitis C virus: A meta-analysis of the risk factors

Proteases and protease inhibitors in infectious diseases

Contact Info

Product

Resources

About