Effects of atazanavir: A Synthesis of Findings from 18 Studies

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Original Abstract of the Article

Major Research Findings

Multiple studies have investigated the effects of atazanavir on HIV-infected individuals. 18 found that atazanavir and darunavir have comparable effects on metabolic parameters. 16 indicated that atazanavir had a slower initial viral decline rate compared to efavirenz and lopinavir. 6 suggested that atazanavir can increase raltegravir plasma concentrations. 11 showed that pitavastatin may impact atherosclerotic inflammatory biomarkers in HIV patients on atazanavir/ritonavir. 13 observed that atazanavir or fosamprenavir might affect rosuvastatin pharmacokinetics. 14 found that tenofovir significantly decreased atazanavir AUC. 10 demonstrated that atazanavir can inhibit and induce P-glycoprotein activity and is a potent CYP3A inhibitor in vitro. 1 highlighted the benefits of atazanavir/ritonavir and darunavir/ritonavir over lopinavir/ritonavir in initial HIV treatment. 17 pointed out the potential cardiotoxicity associated with artemether/lumefantrine and atazanavir/ritonavir combination. 2 showed the potential impact of pitavastatin on lipid profiles in HIV patients on atazanavir/ritonavir. 7 revealed that atazanavir plasma concentrations are reduced with minocycline and valproic acid coadministration. 3 indicated that atazanavir might have conflicting effects on atherosclerotic risk factors in stable HIV patients. 8 showed that ritonavir-boosted darunavir does not affect lipid and glucose parameters in HIV-negative healthy volunteers compared to ritonavir-boosted atazanavir. 12 showed that switching from tenofovir-based to abacavir-based antiretroviral therapy can impact renal function, irrespective of atazanavir use. 4 compared the metabolic effects of ritonavir-boosted darunavir or atazanavir versus raltegravir and highlighted the role of ritonavir plasma exposure. 15 investigated the effects of dolutegravir, darunavir, and atazanavir on osteogenesis to shed light on antiretroviral therapy-induced osteopenia. 9 found that high-fat diet-induced obesity can affect atazanavir pharmacokinetics in rats. 5 explored the effects of atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-negative healthy adults.

Benefits and Risks

Benefit Summary

Atazanavir's primary benefit is its effectiveness in suppressing HIV in infected individuals. Some studies also suggest that atazanavir may have a milder impact on metabolic parameters compared to other protease inhibitors. 18

Risk Summary

Atazanavir poses risks such as dyslipidemia, insulin resistance, and liver function abnormalities. It also has the potential to interact with other medications, requiring careful consideration during coadministration. 10

Comparison Across Studies

Similarities

Multiple studies consistently suggest that atazanavir administration can influence metabolic parameters in HIV-infected individuals. Notably, increased risks of dyslipidemia and insulin resistance have been reported. 18 1 8 4

Differences

The effects and side effects of atazanavir can vary depending on factors such as dosage, coadministered medications, and individual patient characteristics. Some studies highlight the potential for atazanavir to have a milder impact on metabolic parameters compared to other protease inhibitors. 18

Consistency and Contradictions in Findings

Although research collectively suggests that atazanavir administration can affect metabolic parameters in HIV-infected individuals, the extent and mechanisms of these effects vary across studies. 1 3

Practical Implications and Cautions

While atazanavir is an effective medication for treating HIV infection, its potential metabolic impacts and drug interactions necessitate careful adherence to medical guidance. Individuals with pre-existing conditions such as diabetes or dyslipidemia should exercise particular caution. 10 9

Limitations of Current Research

Research on the effects of atazanavir remains incomplete. Future studies should focus on long-term impacts and personalized effect evaluations, considering individual patient characteristics.

Directions for Future Research

Larger-scale studies are needed to gain a more comprehensive understanding of atazanavir's metabolic impacts. Comparative studies with other protease inhibitors are also crucial.

Conclusion

Atazanavir is an effective treatment for HIV infection, but its potential metabolic effects and drug interactions demand careful adherence to medical guidance. Continued research is expected to further clarify the benefits and risks of atazanavir.

Literature analysis of 18 papers
Positive Content
13
Neutral Content
3
Negative Content
2
Article Type
9
0
0
0
18
1.

Early lipid changes with atazanavir/ritonavir or darunavir/ritonavir.

Author: MartinezE, Gonzalez-CordonA, FerrerE, DomingoP, NegredoE, GutierrezF, PortillaJ, CurranA, PodzamczerD, MurillasJ, BernardinoJ I, SantosI, CartonJ A, PeraireJ, PichJ, PerezI, GatellJ M,

Lipid effects
Tolerability
Hyperbilirubinaemia

This study examines the lipid effects and overall tolerability of ritonavir-boosted atazanavir and darunavir compared to ritonavir-boosted lopinavir in patients with HIV infection.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

Effects of Pitavastatin on Lipid Profiles in HIV-Infected Patients with Dyslipidemia and Receiving Atazanavir/Ritonavir: A Randomized, Double-Blind, Crossover Study.

Author: WongprikornAsita, SukasemChonlaphat, PuangpetchApichaya, NumthavejPawin, ThakkinstianAmmarin, KiertiburanakulSasisopin

Pitavastatin effective
Pitavastatin safe

Pitavastatin significantly decreased total cholesterol (TC) and low density lipoprotein (LDL) levels in HIV-infected patients receiving atazanavir/ritonavir (ATV/r) without significant hepatotoxicity or creatine phosphokinase elevation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

3.

Conflicting effects of atazanavir therapy on atherosclerotic risk factors in stable HIV patients: A randomized trial of regimen switch to atazanavir.

Author: BeckmanJoshua A, WoodBrian R, ArdKevin L, PriceChristin N, SolomonDaniel A, ZuflachtJonah P, MilianJessica, PrennerJoshua C, SaxPaul E

Lower CVD risk
Increased von Willebrand Factor

Atazanavir (ATV), an antiretroviral drug, increases bilirubin levels and may improve cardiometabolic risk factors in older patients with HIV. ATV significantly increased serum total bilirubin levels, acutely reduced oxidative stress, and reduced hs-CRP. However, ATV did not improve endothelial function of conduit arteries and increased von Willebrand Factor levels.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

4.

Comparison of the metabolic effects of ritonavir-boosted darunavir or atazanavir versus raltegravir, and the impact of ritonavir plasma exposure: ACTG 5257.

Author: OfotokunIghovwerha, NaLumine H, LandovitzRaphael J, RibaudoHeather J, McComseyGrace A, GodfreyCatherine, AweekaFrancesca, CohnSusan E, SagarManish, KuritzkesDaniel R, BrownTodd T, PattersonKristine B, ParaMichael F, LeavittRandi Y, Villasis-KeeverAngelina, BaughBryan P, LennoxJeffrey L, CurrierJudith S,

Improved lipid profile
Increased LDL cholesterol
Increased total cholesterol
Increased triglycerides

Raltegravir-based combination antiretroviral therapy (cART) produced the most favorable lipid profile compared to ritonavir-boosted atazanavir or darunavir. The metabolic syndrome rates were high at baseline and increased to the same degree in all arms.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

5.

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

Author: NoorMustafa A, ParkerRex A, O'MaraEdward, GraselaDennis M, CurrieAlexander, HodderSally L, FiedorekFred T, HaasDavid W

Less effect on glucose transport
Insulin resistance
Type 2 diabetes

Atazanavir is a new HIV protease inhibitor that has a lower impact on insulin sensitivity compared to other protease inhibitors, potentially reducing the risk of insulin resistance and type 2 diabetes mellitus.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

6.

Exposure-related effects of atazanavir on the pharmacokinetics of raltegravir in HIV-1-infected patients.

Author: CattaneoDario, RipamontiDiego, BaldelliSara, CozziValeria, ContiFrancesca, ClementiEmilio

Increased RAL plasma concentrations

Atazanavir (ATV) significantly increased plasma concentrations of raltegravir (RAL) in HIV-infected patients, especially those exposed to high ATV concentrations.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Effects of minocycline and valproic acid coadministration on atazanavir plasma concentrations in human immunodeficiency virus-infected adults receiving atazanavir-ritonavir.

Author: DiCenzoRobert, PetersonDerick R, CruttendenKim, MariuzPeter, RezkNaser L, HochreiterJill, GelbardHarris, SchifittoGiovanni

HIV-associated cognitive impairment treatment
Decreased atazanavir exposure

This study investigated the effect of minocycline and valproic acid on atazanavir plasma concentrations in HIV-infected subjects. Coadministration of minocycline and valproic acid resulted in decreased atazanavir exposure, suggesting potential drug interactions that need to be considered in clinical practice.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Effects of ritonavir-boosted darunavir vs. ritonavir-boosted atazanavir on lipid and glucose parameters in HIV-negative, healthy volunteers.

Author: TomakaF, LefebvreE, SekarV, Van BaelenB, VangeneugdenT, VandevoordeA, Diego MirallesG

Hyperbilirubinemia

Darunavir plus low-dose ritonavir and atazanavir plus low-dose ritonavir resulted in minor and similar changes in lipid and glucose parameters in healthy volunteers.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Effects of obesity induced by high-fat diet on the pharmacokinetics of atazanavir in rats.

Author: KobuchiShinji, FukushimaKeizo, AoyamaHiroaki, ItoYukako, SugiokaNobuyuki, TakadaKanji

ATV efficacy reduced
Hepatic metabolism decreased

This study investigated the effects of obesity on the pharmacokinetics of atazanavir (ATV) in a rat model of high-fat diet-induced obesity. The study found that ATV exposure was significantly greater in obese rats than in control rats, suggesting that dosing regimens may need to be adjusted in obese patients to ensure optimal therapeutic effect.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Atazanavir: effects on P-glycoprotein transport and CYP3A metabolism in vitro.

Author: PerloffElke S, DuanSu X, SkolnikPaul R, GreenblattDavid J, von MoltkeLisa L

Drug-drug interactions

This study evaluated the effect of atazanavir on P-glycoprotein (P-gp) expression and activity, as well as its inhibitory potency against CYP3A activity, in vitro.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

11.

Effects of pitavastatin on atherosclerotic-associated inflammatory biomarkers in people living with HIV with dyslipidemia and receiving ritonavir-boosted atazanavir: a randomized, double-blind, crossover study.

Author: SrichatrapimukSirawat, WongsaArtit, SungkanuparphSomnuek, KiertiburanakulSasisopin, TassaneetrithepBoonrat, PhuphuakratAngsana

Inflammation reduction

This study investigates the effect of pitavastatin, a statin medication, on inflammatory biomarkers in people living with HIV (PLHIV) receiving antiretroviral therapy (ART).

Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Effects of atazanavir/ritonavir or fosamprenavir/ritonavir on the pharmacokinetics of rosuvastatin.

Author: BustiAnthony J, BainAmy M, HallRonald G, BedimoRoger G, LeffRichard D, MeekClaudia, MehvarReza

Rosuvastatin is a cholesterol-lowering drug, but it can interact with other medications. This study will investigate how rosuvastatin interacts with atazanavir/ritonavir or fosamprenavir/ritonavir, which are HIV medications.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Unveiling the basis of antiretroviral therapy-induced osteopenia: the effects of Dolutegravir, Darunavir and Atazanavir on osteogenesis.

Author: CazzanigaAlessandra, ScrimieriRoberta, GalliMassimo, MaierJeanette, RusconiStefano

Impaired osteogenesis

Atazanavir and Dolutegravir, two commonly used antiretroviral drugs, were found to impair osteogenesis in human mesenchymal stem cells and osteoblasts, while Darunavir had no effect. This finding highlights the importance of early diagnosis and therapeutic interventions to preserve bone health in ART-treated HIV patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients.

Author: EdénArvid, AnderssonLars-Magnus, AnderssonOrjan, FlamholcLeo, JosephsonFilip, NilssonStaffan, OrmaasenVidar, SvedhemVeronica, SällChrister, SönnerborgAnders, TunbäckPetra, GisslénMagnus

Rapid viral decay

This study compared the initial viral decay rate of three different antiretroviral regimens: efavirenz (EFV), lopinavir/ritonavir (LPV/r), and atazanavir/ritonavir (ATV/r). The researchers found that EFV-based treatment resulted in a more rapid decline in HIV-1 RNA than either of the boosted protease inhibitor-based regimens.

Clinical Trial, Phase IVPost-marketing surveillance. Monitors long-term safety/efficacy after approval.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Effects of once-daily darunavir/ritonavir versus atazanavir/ritonavir on insulin sensitivity in HIV-infected persons over 48 weeks: results of an exploratory substudy of METABOLIK, a phase 4, randomized trial.

Author: OvertonEdgar Turner, TebasPablo, CoateBruce, RyanRobert, PerniciaroAmy, DayaramYaswant K, De La RosaGuy, BaughBryan P

Darunavir with low-dose ritonavir (DRV/r) and atazanavir with low-dose ritonavir (ATV/r) are antiretroviral medications. This study assessed the effects of these agents on insulin sensitivity.

Clinical Trial, Phase IVPost-marketing surveillance. Monitors long-term safety/efficacy after approval.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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