Effects of entrectinib: A Synthesis of Findings from 7 Studies

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Original Abstract of the Article

Major Research Findings

Efavirenz is known for its cognitive side effects. Even asymptomatic patients who switch to other medications for reasons other than neurocognitive complaints have reported subjective improvement in cognitive function after stopping efavirenz. 7 . A study aimed to assess the impact on cognition of switching from Atripla (TDF/FTC/EFV) to Eviplera (TDF/FTC/RPV), hypothesizing an improvement when discontinuing efavirenz. 7 .

Antiretroviral therapy containing efavirenz may affect cognitive function, while treatment with lopinavir/ritonavir may increase cholesterol levels. 6 . Lopinavir/ritonavir has been shown to increase cholesterol levels by promoting cholesterol absorption. 6 .

A study comparing daily efavirenz doses of 400mg and 600mg in treatment-naive patients found that both doses were virologically non-inferior at 48 weeks. 4 . However, the 400mg dose group had significantly lower efavirenz blood concentrations. 4 .

A study following participants for over 3 years on efavirenz-based regimens found that neuropsychological performance continued to improve from baseline. 1 . However, there were small increases in efavirenz-related symptoms, bad dreams, and anxiety from baseline. 1 .

A crossover trial comparing efavirenz and etravirine found no significant preference for either treatment among patients and no measurable impact on neuropsychiatric symptoms or sleep. 2 . Cholesterol levels significantly decreased when switching to etravirine. 2 .

Efavirenz may be neurotoxic, which could lead to cognitive impairment. 3 . Efavirenz and its major metabolite, 8-hydroxy-efavirenz, have been shown to be toxic to neurons in culture at concentrations found in cerebrospinal fluid. 3 .

A pilot randomized, placebo-controlled trial investigating the effect of valerian in preventing neuropsychiatric side effects of efavirenz in HIV-positive patients found that valerian significantly improved sleep and anxiety in the first 4 weeks of ART. 5 . However, valerian may cause side effects such as dizziness and nausea. 5 .

Benefits and Risks

Benefit Summary

Efavirenz is an effective antiretroviral drug for the treatment of HIV infection. Efavirenz can slow the progression of HIV infection by suppressing viral load and increasing CD4 cell counts. 1 . It can also be used in combination with other antiretrovirals for more effective HIV treatment. 1 .

Risk Summary

Efavirenz may cause neuropsychiatric side effects such as cognitive impairment, sleep disturbances, anxiety, and nightmares. 1 . It may also cause side effects such as dizziness and nausea. 5 . Efavirenz may be neurotoxic, which could lead to cognitive impairment. 3 .

Comparison of Studies

Commonalities

These studies show that efavirenz is effective in treating HIV infection. They also indicate that efavirenz can cause neuropsychiatric side effects. Additionally, these studies suggest that the effects and side effects of efavirenz may vary depending on dosage and co-administered medications.

Differences

The studies differ in terms of the target patient population, study duration, and evaluation criteria. Therefore, direct comparison of the study results is not possible. For example, one study compares efavirenz doses, while another study compares the combined effects of efavirenz with other antiretrovirals. Therefore, it is necessary to interpret the findings of these studies comprehensively.

Consistency and Contradictions in Results

The findings of these studies suggest that efavirenz may impact cognitive function. However, the extent to which efavirenz affects cognitive function varies among individuals, and it is still unclear how significant the impact is. Furthermore, the impact may differ based on efavirenz dosage and co-administered medications. Additionally, the long-term health implications of efavirenz's cognitive impact remain unclear. Therefore, further research on the cognitive effects of efavirenz is needed.

Practical Application Considerations

Efavirenz is an effective antiretroviral drug for the treatment of HIV infection. However, it may cause neuropsychiatric side effects such as cognitive impairment, sleep disturbances, anxiety, and nightmares. Therefore, it is important to be aware of these side effects when taking efavirenz. Also, follow your doctor's instructions and take the appropriate dose. Efavirenz can interact with other medications, so always inform your doctor about any other medications you are taking.

Limitations of Current Research

These studies have several limitations. First, they are relatively small in scale and have a limited number of participants. Therefore, further research is needed to generalize the findings. Also, because the studies differ in terms of efavirenz dosage and co-administered medications, direct comparison of the results is not possible. Furthermore, different methods were used to evaluate the impact of efavirenz on cognitive function in these studies. Therefore, it is important to be mindful of these points when comparing study results.

Future Research Directions

Further research on the cognitive impact of efavirenz is needed. In particular, the long-term health implications of efavirenz's cognitive impact remain unclear. Therefore, long-term follow-up studies on the cognitive impact of efavirenz are necessary. Also, research is needed on methods to mitigate the cognitive impact of efavirenz. For example, adjusting the dosage of efavirenz or using it in combination with other antiretrovirals may reduce the cognitive impact. Additionally, research is needed to identify patients who are more susceptible to the cognitive impact of efavirenz. For example, factors such as age, sex, and genotype may influence the cognitive impact of efavirenz.

Conclusion

Efavirenz is an effective antiretroviral drug for the treatment of HIV infection. However, it may cause neuropsychiatric side effects such as cognitive impairment, sleep disturbances, anxiety, and nightmares. Be mindful of these side effects when taking efavirenz. Additionally, efavirenz may be neurotoxic, which could lead to cognitive impairment. Therefore, further research on the cognitive impact of efavirenz is needed. Consult with your doctor if you have concerns about taking efavirenz.

Literature analysis of 7 papers
Positive Content
5
Neutral Content
2
Negative Content
0
Article Type
6
0
1
1
7
1.

Long-term impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals (ACTG 5097s).

Author: CliffordDavid B, EvansScott, YangYijun, AcostaEdward P, RibaudoHeather, GulickRoy M,

Improved neuropsychological performance
Increased CNS symptoms
Increased anxiety

In patients continuing EFV-based regimens for more than 3 years, neuropsychological performance improved from baseline and was maintained. However, small increases in EFV-associated symptoms, bad dreams, and anxiety were observed.

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, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

2.

A randomized crossover study to compare efavirenz and etravirine treatment.

Author: NguyenAlain, CalmyAlexandra, DelhumeauCécile, MercierIsabelle K, CavassiniMatthias, Fayet-MelloAurélie, ElziLuigia, GennéDaniel, RauchAndri, BernasconiEnos, HirschelBernard,

Reduced cholesterol

This study found that patients did not express a significant preference for etravirine over efavirenz after substitution. There was no measurable effect on neuropsychiatric symptoms and sleep. Cholesterol levels decreased after replacing efavirenz with etravirine.

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

3.

Neuronal toxicity of efavirenz: a systematic review.

Author: DecloedtEric H, MaartensGary

Neurocognitive improvement
Cognitive impairment
Neuron damage
Neuropsychiatric side effects

Efavirenz may contribute to cognitive impairment by damaging nerve cells. Further research is needed to confirm this effect.

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.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

4.

Pharmacokinetic and Pharmacodynamic Comparison of Once-Daily Efavirenz (400 mg vs. 600 mg) in Treatment-Naïve HIV-Infected Patients: Results of the ENCORE1 Study.

Author: DickinsonL, AminJ, ElseL, BoffitoM, EganD, OwenA, KhooS, BackD, OrrellC, ClarkeA, LossoM, PhanuphakP, CareyD, CooperD A, EmeryS, PulsR,

HIV suppression
Efavirenz side effects

Efavirenz 400mg daily was as effective as 600mg daily in suppressing HIV in treatment-naïve patients, despite significantly lower exposure at the lower dose. 97% of patients on 400mg and 98% of patients on 600mg achieved a viral load below 200 copies/mL after 48 weeks.

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

5.

Effect of Valerian in Preventing Neuropsychiatric Adverse Effects of Efavirenz in HIV-Positive Patients: A Pilot Randomized, Placebo-Controlled Clinical Trial.

Author: AhmadiMotahareh, KhaliliHossein, AbbasianLadan, GhaeliPadideh

Improved sleep
Reduced anxiety
Dizziness
Nausea

Valerian significantly improved sleep and anxiety in HIV-positive patients receiving efavirenz. Valerian may be a potential option for preventing neuropsychiatric adverse effects of efavirenz.

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

6.

Increased cholesterol absorption rather than synthesis is involved in boosted protease inhibitor-associated hypercholesterolaemia.

Author: LeyesPere, CofanMontserrat, González-CordónAna, de LazzariElisa, TrabalJoan, DomingoPere, NegredoEugenia, VidalFrancesc, ForgaMaria T, GatellJose M, RosEmili, MartínezEsteban

Increased cholesterol

Ritonavir-boosted lopinavir (LPV/r)-based therapy increased total cholesterol levels compared to efavirenz (EFV)-based therapy in HIV-infected patients. The increased total cholesterol levels were likely due to increased cholesterol absorption rather than increased cholesterol synthesis.

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.
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

7.

Objective and Subjective Improvement of Cognition After Discontinuing Efavirenz in Asymptomatic Patients: A Randomized Controlled Trial.

Author: HakkersCharlotte S, ArendsJoop E, van den BerkGuido E, EnsingMonique H M, HooijengaImke, VinkMatthijs, van ZandvoortMartine J E, HoepelmanAndy I M

Improved cognitive functioning
Cognitive side effects

This study assessed the effect on cognition of switching Atripla (TDF/FTC/EFV) to Eviplera (TDF/FTC/RPV), hypothesizing an improvement when discontinuing efavirenz.

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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