Effects of dolutegravir: A Synthesis of Findings from 19 Studies

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Original Abstract of the Article

Major Findings

Dolutegravir is a potent and well-tolerated antiretroviral medication used in the treatment of HIV infection. 3 、 2 、 16 、 12 、、 14 、 1 、 11 、 8 、 7 、 17 、、 10 、 19 、 15 、 4 、 5 、 13 、 6 However, it can interact with other medications. 3 、 1 、 11 、 19 It can also cause neuropsychiatric adverse effects in some patients. 14 、

Benefits and Risks

Benefits Summary

Dolutegravir is a potent and well-tolerated antiretroviral medication used in the treatment of HIV infection. 、 14 Dolutegravir is associated with improved antiretroviral potency, CD4+ T cell preservation, and tolerability compared to previous regimens. 10 It is a first-line treatment option due to its efficacy and safety profile. 14 、 10

Risks Summary

Dolutegravir can interact with other medications. 3 、 1 、 11 、 19 It can also cause neuropsychiatric adverse effects in some patients. 14 、 Therefore, it is crucial to discuss potential interactions with your doctor and ensure you adhere to prescribed dosages and regimens.

Study Comparison

Similarities

Multiple studies investigated the effectiveness and safety of dolutegravir. 3 、 2 、 16 、 12 、、 14 、 1 、 11 、 8 、 7 、 17 、、 10 、 19 、 15 、 4 、 5 、 13 、 6 These studies highlight its effectiveness in managing HIV infection. They provide valuable insights into dolutegravir's pharmacokinetics, potential adverse effects, and drug interactions.

Differences

These studies varied in their objectives and methodologies. For instance, some studies focused on dolutegravir's pharmacokinetics. 3 、 2 、 1 、 11 Others investigated its adverse effects. 14 、 Some research focused on interactions with other medications. 3 、 1 、 11 、 19 Synthesizing findings from these diverse studies allows for a comprehensive understanding of dolutegravir's effects and safety profile.

Consistency and Contradictions

While many studies suggest dolutegravir's effectiveness and safety, some research indicates the possibility of neuropsychiatric adverse effects and interactions with other medications. 14 、、 3 、 1 、 11 、 19 Therefore, adhering to your doctor's instructions and discussing any potential interactions with other medications is crucial when taking dolutegravir.

Practical Implications and Considerations

Dolutegravir holds promise as an effective treatment option for HIV infection. 10 However, it's important to be aware of the potential for neuropsychiatric adverse effects and drug interactions. 14 、、 3 、 1 、 11 、 19 It's essential to follow your doctor's directions carefully and discuss any concerns or interactions with other medications.

Limitations of Current Research

The research on dolutegravir's effects and safety is still limited. 15 、 4 Specifically, long-term effects need further investigation. More research is also necessary to understand dolutegravir's adverse effects and interactions with other medications.

Future Research Directions

Future research should focus on the long-term effects, adverse effects, and drug interactions of dolutegravir. 15 、 4 Studies with diverse populations are also needed to gain a more comprehensive understanding of dolutegravir's effects.

Conclusion

Dolutegravir shows promise as an effective treatment option for HIV infection. 10 However, it's crucial to be aware of potential neuropsychiatric adverse effects and drug interactions. 14 、、 3 、 1 、 11 、 19 Always follow your doctor's instructions carefully and discuss any concerns or interactions with other medications.

Literature analysis of 19 papers
Positive Content
16
Neutral Content
1
Negative Content
2
Article Type
6
1
0
0
19
1.

Effects of etravirine alone and with ritonavir-boosted protease inhibitors on the pharmacokinetics of dolutegravir.

Author: SongIvy, BorlandJulie, MinSherene, LouYu, ChenShuguang, PatelParul, WajimaToshihiro, PiscitelliStephen C

Drug interactions

This study evaluated the effects of etravirine (ETR) on the pharmacokinetics (PK) of dolutegravir (DTG), an unboosted, once-daily integrase inhibitor. The study found that ETR significantly decreased DTG exposure. The combination of DTG and ETR alone should be avoided; however, DTG may be coadministered with ETR without a dosage adjustment if lopinavir/ritonavir or darunavir/ritonavir is concurrently administered.

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

2.

Evaluation of the effect of UGT1A1 polymorphisms on dolutegravir pharmacokinetics.

Author: ChenShuguang, St JeanPamela, BorlandJulie, SongIvy, YeoAstrid J, PiscitelliStephen, RubioJustin P

Dolutegravir safe for UGT1A1 variants

Carriers of UGT1A1 reduced function polymorphisms did not experience clinically significant increases in dolutegravir exposure, so dose adjustment is not required.

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.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir.

Author: JohnsonMark, BorlandJulie, ChenShuguang, SavinaPaul, WynneBrian, PiscitelliStephen

Dolutegravir can be coadministered with boceprevir or telaprevir in patients coinfected with HIV and HCV with no dose adjustment.

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.

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

5.

Effects of Low- and High-Mineral Content Water on the Relative Bioavailability of a Coformulated Abacavir/Dolutegravir/Lamivudine Dispersible Tablet in Healthy Adults.

Author: SinghRajendra P, ShaikJafar S B, SkouraNancy, JoshiShashidhar, ShreevesTrevor, CasillasLinda, BuchananAnn M

HIV-1 treatment

A fixed-dose combination tablet of abacavir/dolutegravir/lamivudine is available for HIV-1 infection in adults and children weighing at least 40 kg, but alternative formulations are needed for younger children.

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

6.

Effects of raltegravir or elvitegravir resistance signature mutations on the barrier to dolutegravir resistance in vitro.

Author: SekiTakahiro, Suyama-KagitaniAkemi, Kawauchi-MikiShinobu, MikiShigeru, Wakasa-MorimotoChiaki, AkihisaErika, NakaharaKoichiro, KobayashiMasanori, UnderwoodMark R, SatoAkihiko, FujiwaraTamio, YoshinagaTomokazu

High barrier to resistance
DTG resistance via Q148 pathway

This study examined the resistance profile of dolutegravir (DTG), a new HIV-1 integrase strand transfer inhibitor (INSTI), against various HIV-1 mutations. DTG was found to have a high barrier to resistance in the presence of mutations associated with resistance to other INSTIs, such as raltegravir and elvitegravir.

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.

Virological outcomes and metabolic effects after switching from ritonavir-boosted protease inhibitors to a dolutegravir-based regimen in virologically suppressed patients living with HIV.

Author: SribenjaluxWantin, NuntawitTharatorn, MeesingAtibordee, ChetchotisakdPloenchan

Improved blood lipid levels
Abnormal lipid levels
Cardiovascular disease

This study investigates the impact of switching from a ritonavir-boosted protease inhibitor (PI)-based antiretroviral therapy (ART) regimen to a dolutegravir (DTG)-based regimen on lipid levels in Thai patients living with HIV. PI-based ART regimens are associated with abnormal lipid levels and an increased risk of cardiovascular disease. This study evaluates the effects of switching to DTG-based ART on blood lipid levels in the Thai population, providing valuable data on the potential benefits of this switch in improving cardiovascular health.

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, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

The Integrase Inhibitors Dolutegravir and Raltegravir Exert Proadipogenic and Profibrotic Effects and Induce Insulin Resistance in Human/Simian Adipose Tissue and Human Adipocytes.

Author: GorwoodJennifer, BourgeoisChristine, PourcherValérie, PourcherGuillaume, CharlotteFrédéric, ManteconMatthieu, RoseCindy, MorichonRomain, AtlanMichael, Le GrandRoger, DesjardinsDelphine, KatlamaChristine, FèveBruno, LambotteOlivier, CapeauJacqueline, BéréziatVéronique, LagathuClaire

Adipose tissue gain

This study used human and simian models to assess the impact of INSTIs on adipose tissue phenotype and function. INSTIs are a class of drugs used to treat HIV infection.

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

9.

Effects of etravirine alone and with ritonavir-boosted protease inhibitors on the pharmacokinetics of dolutegravir.

Author: SongIvy, BorlandJulie, MinSherene, LouYu, ChenShuguang, PatelParul, WajimaToshihiro, PiscitelliStephen C

Drug interactions

This study evaluated the effects of etravirine (ETR) on the pharmacokinetics (PK) of dolutegravir (DTG), an unboosted, once-daily integrase inhibitor. The study found that ETR significantly decreased DTG exposure. The combination of DTG and ETR alone should be avoided; however, DTG may be coadministered with ETR without a dosage adjustment if lopinavir/ritonavir or darunavir/ritonavir is concurrently administered.

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.

Combined cART including Tenofovir Disoproxil, Emtricitabine, and Dolutegravir has potent therapeutic effects in HIV-1 infected humanized mice.

Author: WeichseldorferMatthew, AfframYvonne, HerediaAlonso, Rikhtegaran-TehraniZahra, SajadiMohammad M, WilliamsSumiko P, TagayaYutaka, BenedettiFrancesca, RamadhaniHabib O, DenaroFrank, MunawwarArshi, BryantJoseph, ZellaDavide, ReitzMarvin, RomerioFabio, LatinovicOlga S

HIV-1 treatment

The CD34+ hematopoietic humanized mouse model was further validated as a pre-clinical model to study HIV-1 infection and therapy. The model showed viral suppression with a recently developed combination of antiretrovirals and identified specific solid tissue reservoirs of infected cells.

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

11.

Effects of enzyme inducers efavirenz and tipranavir/ritonavir on the pharmacokinetics of the HIV integrase inhibitor dolutegravir.

Author: SongIvy, BorlandJulie, ChenShuguang, GutaPhyllis, LouYu, WilfretDavid, WajimaToshihiro, SavinaPaul, PeppercornAmanda, CastellinoStephen, WagnerDavid, HoskingLouise, MostellerMichael, RubioJustin P, PiscitelliStephen C

HIV treatment
Increased DTG dose

Dolutegravir (DTG) should be administered at a higher dose (50 mg twice daily) when co-administered with efavirenz (EFV) or tipranavir/ritonavir (TPV/r) due to the significant reduction in DTG exposure. Alternative regimens without inducers should be considered for integrase inhibitor-resistant patients.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard treatment.
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.

Switching from boosted PIs to dolutegravir in HIV-infected patients with high cardiovascular risk: 48 week effects on subclinical cardiovascular disease.

Author: Gonzalez-CordonAna, AssoumouLambert, CamafortMiguel, DomenechMonica, GuaraldiGiovanni, DomingoPere, RusconiStefano, RaffiFrançois, KatlamaChristine, MasiaMar, BernardinoJose I, SaumoyMaria, PozniakAnton, GatellJose M, MartinezEsteban,

cardiovascular risk reduction

This trial investigated the impact of switching from boosted protease inhibitors (PIs) to dolutegravir on subclinical cardiovascular disease in virologically suppressed HIV-infected patients with high cardiovascular risk. While switching to dolutegravir showed favorable trends in intima-media thickness (CIMT) progression, the difference was not statistically significant. Further research is needed to confirm the long-term cardiovascular benefits of switching to dolutegravir in this population.

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

16.

Differential effects of dolutegravir, bictegravir and raltegravir in adipokines and inflammation markers on human adipocytes.

Author: DomingoPere, Quesada-LópezTania, VillarroyaJoan, CairóMontserrat, GutierrezMaria Del Mar, MateoMaria Gracia, MurIsabel, CorbachoNoemí, DomingoJoan Carles, VillarroyaFrancesc, GiraltMarta

Metabolic dysregulation

This study assessed the direct effects of integrase strand-transfer inhibitors (INsTIs) on human adipose cells. The INsTIs did not significantly affect adipocyte differentiation but had distinct effects on gene expression and secretion of adipokines and cytokines.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

17.

Effects of Injection Volume and Route of Administration on Dolutegravir In Situ Forming Implant Pharmacokinetics.

Author: JoinerJordan B, KingJasmine L, ShrivastavaRoopali, HowardSarah Anne, CottrellMackenzie L, KashubaAngela D M, DaytonPaul A, BenhabbourSoumya Rahima

This study investigated the impact of formulation parameters on the performance of in situ forming implants (ISFIs). Ultrasound imaging and pharmacokinetics (PK) in mice revealed that drug loading and injection volume significantly influenced ISFI formation, degradation, and drug release.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

18.

Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir.

Author: JohnsonMark, BorlandJulie, ChenShuguang, SavinaPaul, WynneBrian, PiscitelliStephen

Dolutegravir can be coadministered with boceprevir or telaprevir in patients coinfected with HIV and HCV with no dose adjustment.

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

19.

Effects of the androgen receptor inhibitor enzalutamide on the pharmacokinetics of dolutegravir and tenofovir: a case report.

Author: LonderoAngela, FusiMarta, CinauseroMarika, TasciniCarlo, GervasoniCristina, CattaneoDario

Prostate cancer treatment
Drug-drug interactions

This case report investigated the potential drug-drug interactions between enzalutamide and antiretrovirals in a patient with HIV and prostate cancer. No major differences were observed in dolutegravir and tenofovir pharmacokinetics.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
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

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