Effects of ritonavir: A Synthesis of Findings from 13 Studies

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Original Abstract of the Article

Major Research Findings

Ritonavir is an effective antiretroviral drug for HIV-infected individuals. Studies have shown that ritonavir can suppress viral load and increase CD4 cell count in HIV-infected patients. 1 Additionally, ritonavir can interact with other drugs, potentially altering their metabolism and affecting their efficacy. For instance, ritonavir was shown to increase the blood concentration of trazodone, a drug used for depression, by inhibiting its metabolism. 4 Ritonavir also interacts with rifabutin, an antibiotic, leading to increased blood levels of rifabutin and its metabolite. 3 Furthermore, ritonavir can contribute to metabolic complications like elevated blood sugar levels and lipid abnormalities. However, research indicates that atazanavir/ritonavir may have a less detrimental impact on glucose metabolism compared to lopinavir/ritonavir. 5 Besides, ritonavir is associated with high triglyceride levels, and this correlation is observed with the drug's blood concentration. 2 Importantly, research suggests that ritonavir does not negatively affect neurocognitive function or brain imaging in HIV-infected individuals. 13 However, due to its potential for drug interactions, particularly with drugs metabolized via CYP3A, careful consideration is needed when ritonavir is used in combination with other medications. 4 As ritonavir can increase the risk of side effects when used with other antiretroviral drugs, proper monitoring is crucial. 11 While ritonavir is a beneficial drug for treating HIV, it is important to acknowledge its potential side effects.

Benefits and Risks

Benefit Summary

Ritonavir effectively suppresses viral load in HIV-infected individuals, contributing to improved immune function. 1 Ritonavir can enhance the effectiveness of other antiretroviral drugs by increasing their blood levels. 3 Ritonavir can improve the quality of life for HIV-infected individuals by managing the infection.

Risk Summary

Ritonavir can lead to side effects like elevated blood sugar levels and lipid abnormalities. 5 Ritonavir is also associated with increased triglyceride levels. 2 Ritonavir can interact with other medications, requiring caution when used in combination. 4 It is crucial to be aware of the potential side effects associated with ritonavir.

Comparison Across Studies

Commonalities Across Studies

Multiple studies consistently demonstrate the effectiveness of ritonavir in suppressing viral load and increasing CD4 cell count in HIV-infected individuals. 1 10 13 Several studies also highlight the potential of ritonavir to affect the metabolism of other drugs. 3 4 Additionally, studies underscore the increased risk of side effects when ritonavir is used in combination with other antiretroviral drugs. 11 9

Differences Across Studies

Studies vary in terms of the concentration and duration of ritonavir used, the effects observed, and the risk of side effects associated with the drug.

Consistency and Discrepancies in Findings

Research consistently demonstrates ritonavir's effectiveness in suppressing viral load and increasing CD4 cell count in HIV-infected individuals. 1 10 13 However, the optimal concentration and duration of ritonavir use, the specific effects observed, and the associated risk of side effects remain points of variation among studies.

Practical Implications and Considerations

Ritonavir is an effective drug for treating HIV but carries potential side effects that should be considered. 4 Ritonavir can interact with other medications, necessitating caution when used in combination. 4 The combination of ritonavir with other antiretroviral drugs can increase the risk of side effects, highlighting the importance of monitoring by healthcare professionals. 11 It is crucial to follow medical advice when taking ritonavir.

Limitations of Current Research

The long-term effects of using ritonavir are not yet fully understood. More research is needed to assess the long-term impact of ritonavir on individuals.

Future Research Directions

Further investigation is necessary to understand the long-term consequences of ritonavir use. Additionally, more detailed research is required to analyze the interactions between ritonavir and other medications.

Conclusion

Ritonavir is an effective drug for suppressing viral load and improving immune function in HIV-infected individuals. 1 Ritonavir can also enhance the effectiveness of other antiretroviral drugs by increasing their blood levels. 3 Ritonavir can contribute to improving the quality of life for HIV-infected individuals by managing the infection. 10 However, ritonavir can cause side effects like elevated blood sugar levels and lipid abnormalities. 5 It is important to be aware of the potential for drug interactions when ritonavir is used in combination with other medications. 4 Following medical advice when taking ritonavir is essential.

Literature analysis of 13 papers
Positive Content
11
Neutral Content
0
Negative Content
2
Article Type
12
1
0
0
13
1.

Alterations in the immune response of human immunodeficiency virus (HIV)-infected subjects treated with an HIV-specific protease inhibitor, ritonavir.

Author: KelleherA D, CarrA, ZaundersJ, CooperD A

HIV-1 infection treatment
Immune system improvement

Ritonavir, an HIV-1 protease inhibitor, significantly increased CD4 and CD8 lymphocyte counts and improved immune function in 21 patients.

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.
Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
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.

Multiple-dose pharmacokinetics of ritonavir in human immunodeficiency virus-infected subjects.

Author: HsuA, GrannemanG R, WittG, LockeC, DenissenJ, MollaA, ValdesJ, SmithJ, ErdmanK, LyonsN, NiuP, DecourtJ P, FourtillanJ B, GiraultJ, LeonardJ M

Increased triglyceride levels

Ritonavir, an HIV treatment, showed moderately dose-dependent pharmacokinetics with concentration-dependent autoinduction. Triglyceride levels increased with higher ritonavir doses. This data provides information about its absorption, elimination, and potential side effects.

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.
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.

Language : English

3.

The effect of multiple doses of ritonavir on the pharmacokinetics of rifabutin.

Author: CatoA, CavanaughJ, ShiH, HsuA, LeonardJ, GrannemanR

Increased rifabutin levels

Ritonavir significantly increases the plasma concentrations of rifabutin and its metabolite 25-O-desacetylrifabutin, suggesting that both drugs are metabolized by CYP3A.

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.
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

4.

Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone.

Author: GreenblattDavid J, von MoltkeLisa L, HarmatzJerold S, FogelmanSteven M, ChenGengsheng, GrafJennifer A, MertzanisPolyxane, ByronSusan, CulmKerry E, GrandaBrian W, DailyJohanna P, ShaderRichard I

Drug interactions

Ritonavir significantly reduced apparent oral clearance of trazodone, prolonged elimination half-life, and increased peak plasma concentrations (mean +/- SE). Coadministration of trazodone with ritonavir increased sedation, fatigue, and performance impairment compared to trazodone plus placebo.

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, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

6.

Effects of first-line use of nucleoside analogues, efavirenz, and ritonavir-boosted protease inhibitors on lipid levels.

Author: HillAndrew, SawyerWill, GazzardBrian

Lipid elevation

There is a wide range of lipid elevations during 48 weeks of first-line HAART, depending on the choice of antiretrovirals used.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

7.

The benefit of simplification from tipranavir/ritonavir 500/200 bid to 500/100 bid guided by therapeutic drug monitoring.

Author: MorelloJudit, Rodríguez-NovoaSonia, BlancoFrancisco, VispoEugenia, BarreiroPablo, Gonzalez-PardoGema, Jiménez-NácherInmaculada, González-LahozJuan, SorianoVincent

HIV suppression
Reduced aminotransferases
Reduced cholesterol
Reduced triglycerides
Pill burden
Side effects

Tipranavir is a potent protease inhibitor but has a high pill burden and frequent side effects. This study found that reducing the ritonavir dose in patients taking tipranavir/ritonavir resulted in decreased liver enzymes and cholesterol levels in some patients without affecting viral suppression.

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.

Language : English

8.

Boosting dose ritonavir does not alter peripheral insulin sensitivity in healthy HIV-seronegative volunteers.

Author: TaylorSteven A, LeeGrace A, PaoVivian Y, AnthonypillaiJayaranjan, AweekaFrancesca T, SchwarzJean-Marc, MulliganKathleen, SchambelanMorris, GrunfeldCarl

Insulin resistance

Some HIV protease inhibitors (PIs), including full-dose ritonavir (800 mg) and ritonavir-boosted lopinavir, acutely induce insulin resistance in the absence of HIV infection. The effects of boosting dose ritonavir (100-200 mg) on glucose metabolism have not been described in the absence of another PI.

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.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

9.

Similar efficacy and tolerability of atazanavir compared with atazanavir/ritonavir, each with abacavir/lamivudine after initial suppression with abacavir/lamivudine plus ritonavir-boosted atazanavir in HIV-infected patients.

Author: SquiresKathleen E, YoungBenjamin, DejesusEdwin, BellosNicholaos, MurphyDaniel, ZhaoHenry H, PatelLisa G, RossLisa L, WannamakerPaul G, ShaeferMark S,

HIV treatment
Reduced side effects

Treatment simplification strategies involving induction with a ritonavir (RTV)-boosted protease inhibitor regimen followed by simplification without RTV may offer sustained virologic suppression while minimizing long-term adverse effects associated with RTV.

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.

Language : English

10.

Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV: the role of compartment and CD4-nadir.

Author: GutmannChristine, CusiniAlexia, GünthardHuldrych F, FuxChristoph, HirschelBernard, DecosterdLaurent-Arthur, CavassiniMatthias, YerlySabine, VernazzaPietro L,

Reduced viral load
Treatment failure

Monotherapy with ritonavir-boosted lopinavir was not recommended as a standard strategy for HIV maintenance, especially in patients with a low nadir CD4 cell count. Viral failure was observed in patients with a low nadir CD4 cell count, and further research is needed to understand the role of the central nervous system in monotherapy failure.

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

11.

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

12.

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

13.

Neurocognitive Function and Neuroimaging Markers in Virologically Suppressed HIV-positive Patients Randomized to Ritonavir-boosted Protease Inhibitor Monotherapy or Standard Combination ART: A Cross-sectional Substudy From the PIVOT Trial.

Author: Arenas-PintoAlejandro, StöhrWolfgang, JägerHans Rolf, HaddowLewis, ClarkeAmanda, JohnsonMargaret, ChenFabian, WinstonAlan, GodiClaudia, ThustSteffi, TrombinRita, CairnsJanet, SolankyBhavana S, GolayXavier, PatonNicholas I,

HIV treatment

This study assessed the neurocognitive function and brain imaging markers of patients on ritonavir-boosted protease inhibitor (PI) monotherapy versus standard antiretroviral therapy (ART). There was no difference in neurocognitive impairment between the two groups. However, symptomatic neurocognitive impairment was associated with higher global cortical atrophy scores.

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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