Side Effects of efavirenz: A Synthesis of Findings from 19 Studies

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Original Abstract of the Article

Major Research Findings

Efavirenz is a commonly used antiretroviral drug for HIV treatment, but it is associated with neuropsychiatric side effects. 1 , 19 , 18 , 7 , 16 , 10 , 15 , 8 , 11 , 5 Studies suggest that efavirenz can cause various neuropsychiatric side effects, leading to patients discontinuing their treatment. 17 The side effects can range from sleep disturbances, depression, dizziness, and anxiety. 3 Moreover, there is emerging evidence suggesting that efavirenz use may damage neurons, leading to impaired neurocognitive performance. 2 Efavirenz neurotoxicity can be explained by multiple mechanisms, including altered calcium homeostasis, decreases in brain creatine kinase, mitochondrial damage, increases in brain proinflammatory cytokines, and involvement of the cannabinoid system. 2 Side effects of efavirenz are not consistent across all patients, and factors such as age and hepatitis positivity can influence them. 17 Recent studies have shown that dolutegravir, a new HIV treatment drug replacing efavirenz, has a lower risk of neuropsychiatric side effects. 17 , 8 However, neuropsychiatric side effects have also been reported with dolutegravir, so caution is still needed. 16

Reasons for Side Effects

The exact reasons behind efavirenz's neuropsychiatric side effects are still not fully understood. However, it is believed that efavirenz affects the brain, potentially disrupting neurotransmitter balance or directly affecting nerve cells. 2 Efavirenz may also increase the permeability of the blood-brain barrier, leading to neuropsychiatric side effects. 7

Common Side Effects

Sleep Disturbances

One of the most common side effects of efavirenz is sleep disturbances. 1 Patients may experience symptoms such as nightmares, light sleep, and waking up in the middle of the night. 1

Depression

Efavirenz can also cause depression. 1 Patients may experience symptoms such as a depressed mood, loss of interest or pleasure, and decreased concentration and decision-making abilities. 1

Dizziness

Efavirenz can cause dizziness. 1 Patients may experience symptoms such as lightheadedness, feeling unsteady, and loss of balance. 1

Anxiety

Efavirenz can also cause anxiety. 1 Patients may experience symptoms such as restlessness, increased worry, and a heightened sense of fear. 1

Skin Rash

Efavirenz can cause skin rash. 18 The rash can range from mild to severe. 18

Gastrointestinal Symptoms

Efavirenz can cause gastrointestinal symptoms. 18 Patients may experience symptoms such as nausea, vomiting, abdominal pain, and diarrhea. 18

Blood Abnormalities

Efavirenz can cause blood abnormalities. 18 Patients may experience a decrease in white blood cells or red blood cells. 18

Neurological Abnormalities

Efavirenz can cause neurological abnormalities. 18 Patients may experience symptoms such as paralysis, sensory disturbances, and seizures. 18

Side Effects Management

Sleep Disturbances

To manage sleep disturbances, patients can try relaxing techniques before bed, avoiding caffeine and alcohol, and maintaining a regular sleep schedule. 1 If needed, a doctor may prescribe sleeping medications. 1

Depression

For depression management, it is crucial to consult a psychiatrist and consider getting antidepressants prescribed. 1 Therapy and counseling can also be helpful. 1

Dizziness

To manage dizziness, patients should move slowly, especially when getting up, ensure adequate hydration, and avoid standing for extended periods. 1 Patients can also consult with their doctor to review their medication regimen. 1

Anxiety

Anxiety management techniques include deep breathing exercises, meditation, and exercise. 1 Consult with a doctor to discuss the possibility of revising the medication regimen. 1

Skin Rash

If a skin rash is bothersome, consult a doctor. 18 The doctor can identify the cause of the rash and recommend appropriate treatment. 18

Gastrointestinal Symptoms

If gastrointestinal symptoms are concerning, seek medical attention. 18 A doctor can determine the cause of the symptoms and suggest appropriate treatment. 18

Blood Abnormalities

If blood abnormalities are suspected, consult a doctor for blood tests. 18 The doctor can identify the cause of the blood abnormalities and suggest appropriate treatment. 18

Neurological Abnormalities

If neurological abnormalities are suspected, consult a doctor and undergo appropriate testing. 18 The doctor can identify the cause of the neurological abnormalities and suggest appropriate treatment. 18

Comparison Between Studies

Similarities

Multiple studies suggest that efavirenz can cause neuropsychiatric side effects. 1 , 19 , 18 , 7 , 16 , 10 , 15 , 8 , 11 , 5 The side effects can range from sleep disturbances, depression, dizziness, and anxiety. 3 Moreover, efavirenz can potentially damage neurons, leading to impaired neurocognitive performance. 2

Differences

The incidence and severity of side effects caused by efavirenz vary across studies. 1 , 19 , 18 , 7 , 16 , 10 , 15 , 8 , 11 , 5 These variations may be influenced by factors such as the age, gender, HIV infection history, and presence of other diseases in the study participants. 1 , 17

Real-World Application Cautions

Efavirenz can cause neuropsychiatric side effects. 1 , 19 , 18 , 7 , 16 , 10 , 15 , 8 , 11 , 5 Therefore, when taking efavirenz, it is crucial to consult with a doctor and understand the risks and benefits of the drug. 1 , 19 , 18 , 7 , 16 , 10 , 15 , 8 , 11 , 5 If you experience any neuropsychiatric symptoms while taking efavirenz, consult your doctor immediately. 1 , 19 , 18 , 7 , 16 , 10 , 15 , 8 , 11 , 5

Current Research Limitations

Research on the side effects of efavirenz is still insufficient. 1 , 19 , 18 , 7 , 16 , 10 , 15 , 8 , 11 , 5 Especially, long-term side effects of efavirenz are not fully understood. 2 Furthermore, since efavirenz side effects can vary significantly between patients, further research is required. 1 , 17

Future Research Directions

To better understand efavirenz side effects, further research is necessary, including long-term side effect studies and research on the variability of side effects between patients. 1 , 19 , 18 , 7 , 16 , 10 , 15 , 8 , 11 , 5 Developing new HIV treatment drugs that can replace efavirenz is also important. 17

Conclusion

Efavirenz is an effective drug for HIV treatment but can cause neuropsychiatric side effects. 1 , 19 , 18 , 7 , 16 , 10 , 15 , 8 , 11 , 5 When taking efavirenz, it is crucial to consult with a doctor and understand the risks and benefits of the drug. 1 , 19 , 18 , 7 , 16 , 10 , 15 , 8 , 11 , 5 If you experience any neuropsychiatric symptoms while taking efavirenz, consult your doctor immediately. 1 , 19 , 18 , 7 , 16 , 10 , 15 , 8 , 11 , 5 Side effects of efavirenz are not consistent across all patients, and factors such as age and hepatitis positivity can influence them. 17 To better understand efavirenz side effects, further research is necessary, including long-term side effect studies and research on the variability of side effects between patients. 1 , 19 , 18 , 7 , 16 , 10 , 15 , 8 , 11 , 5 Developing new HIV treatment drugs that can replace efavirenz is also important. 17

Literature analysis of 19 papers
Positive Content
13
Neutral Content
2
Negative Content
4
Article Type
1
0
2
3
18
1.

Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals.

Author: CliffordDavid B, EvansScott, YangYijun, AcostaEdward P, GoodkinKarl, TashimaKaren, SimpsonDavid, DorfmanDavid, RibaudoHeather, GulickRoy M

Improve neuropsychological performance
Neurological symptoms

Efavirenz is an antiretroviral drug that can cause neurologic side effects. A study found that these side effects were more common in the first week of treatment but resolved by week 4. Neuropsychological performance improved in both the efavirenz and the control groups.

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

Language : English

2.

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

3.

A review of trials investigating efavirenz-induced neuropsychiatric side effects and the implications.

Author: GaidaRazia, TruterIlse, GroblerChristoffel, KotzeTheunis, GodmanBrian

Neuropsychiatric side effects

This review analyzed the neuropsychiatric side effects associated with efavirenz in HIV patients. Common side effects included sleep problems, depression, dizziness, and anxiety, which were generally mild and did not require discontinuation of the drug.

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.
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.

Knowledge and perceptions about Dolutegravir and Dolutegravir counselling: a qualitative study among women living with HIV.

Author: ChapolaJohn C, LeeFan, BulaAgatha, RosenbergNora E, TsekaJennifer, ChagomeranaMaganizo, HosseinipourMina C, TangJennifer Hui-Yu

This qualitative study explores the challenges faced by healthcare providers in Malawi during the transition from efavirenz-based to dolutegravir-based antiretroviral therapy (ART) for HIV. The study also examines factors influencing patient decisions to switch or not switch to the new regimen.

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.

Language : English

5.

A prospective study to estimate the incidence and pattern of adverse drug reactions to first-line antiretroviral therapy (tenofovir, efavirenz, and lamivudine).

Author: SinghBoby, GulianiAnkur, HanumanthuVinod, NarangTarun, DograSunil, HandaSanjeev, SharmaAman

HIV treatment
Weight gain
Minimal side effects

The fixed drug combination of tenofovir, efavirenz, and lamivudine (TEL) is a safe and effective first-line antiretroviral therapy (ART) for HIV.

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

Language : English

6.

Impact of weight gain with dolutegravir on antiretroviral adherence and viral suppression in four African countries.

Author: RomoMatthew L, EsberAllahna L, OwuothJohn, MaswaiJonah, Sing'oeiValentine, IroezinduMichael, BahemanaEmmanuel, KibuukaHannah, CavanaughJ Sean, ShahNeha, AkeJulie A, CrowellTrevor A,

HIV viral suppression
Weight gain

Although a substantial proportion of participants experienced weight gain after switching to TLD, there was no significant impact on ART adherence or virological outcomes.

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

Language : English

10.

Late-onset efavirenz toxicity: A descriptive study from Pretoria, South Africa.

Author: MunsamiLyneshree, SchutteClara M, de VilliersMaryke, HiesgenJuliane

Efavirenz toxicity

Late-onset efavirenz toxicity typically presents with ataxia and encephalopathy, but psychosis can also occur. The outcome is usually good after withdrawal, but mortality can be high.

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

Language : English

11.

Efavirenz: History, Development and Future.

Author: CostaBárbara, ValeNuno

HIV-1 infection treatment
PrEP
Reduced side effects
Poor HIV suppression
Toxicity

This study reviews the use of efavirenz (Sustiva<sup>®</sup>) for treating HIV-1 infection. While previously a primary first-line antiviral drug, the emergence of integrase strand transfer inhibitors (INSTIs) has led to a shift in treatment strategies. Efavirenz remains a viable option for pre-exposure prophylaxis (PrEP) and repurposing in medicine.

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

Language : English

12.

Clinical predictors of efavirenz-based regimen treatment durability: A two-year case-control study of antiretroviral-naïve patients.

Author: FahrniMathumalar Loganathan, MisranNurul Fatin Laila, AbidinZarena Zainul, ChidambaramSuresh Kumar, LazzarinoAntonio Ivan

Viral suppression
Opportunistic infections
Treatment interruption

Efavirenz-associated adverse drug events were associated with a significant increase in treatment interruption. Intravenous drug use, opportunistic infections, and serious adverse events were independent predictors of treatment interruption.

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

Language : English

15.

Dolutegravir in real life: Self-reported mental and physical health outcomes after transitioning from efavirenz- to dolutegravir-based antiretroviral therapy in a prospective cohort study in Lesotho.

Author: BrownJennifer A, NsakalaBienvenu L, MokheleKuena, RakuoaneItumeleng, MuhairweJosephine, GlassTracy R, AmstutzAlain, TschumiNadine, BelusJennifer M, KlimkaitThomas, LabhardtNiklaus D

DTG transition evaluation
Mental health assessment
Neuropsychiatric effects

This study assesses the mental health and HIV/ART-associated symptoms of people living with HIV before and after transitioning from efavirenz (EFV) to dolutegravir (DTG)-containing antiretroviral therapy (ART).

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

17.

Integrase Inhibitors are Associated with Neuropsychiatric Symptoms in Women with HIV.

Author: RubinLeah H, O'HalloranJane A, WilliamsDionna W, LiYuliang, FitzgeraldKathryn C, DastgheybRaha, DamronAlexandra L, MakiPauline M, SpenceAmanda B, SharmaAnjali, GustafsonDeborah R, MilamJoel, WeberKathleen M, AdimoraAdaora A, OfotokunIgho, FischlMargaret A, Konkle-ParkerDeborah, XuYanxun

Neuropsychiatric symptoms

This study investigated the association between integrase strand transfer inhibitors (INSTIs) and neuropsychiatric symptoms in women with HIV (WWH). INSTIs, but not efavirenz, were associated with increased stress, anxiety, and avoidance symptoms in certain subgroups of WWH.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

18.

Short-Term Adverse Drug Reactions to Antiretroviral Therapy in Children with HIV: A Cohort Study.

Author: RaySandip, SethAnju, SinghSarita, SharmaGarima, GaurNeha, ShahYukti, KumarPraveen, ChandraJagdish

ART
HIV infection
ADRs

Adverse drug reactions (ADRs) to antiretroviral therapy (ART) are very frequent in children with HIV infection. Most ADRs are mild and self-limiting, but they can impact adherence to ART.

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

Language : English

19.

Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand.

Author: PhongsamartWanatpreeya, JantarabenjakulWatsamon, ChantaratinSasitorn, AnugulruengkittSuvaporn, SuntarattiwongPiyarat, SirikuttPakpen, KosalaraksaPope, MaleesatharnAlan, ChokephaibulkitKulkanya

HIV treatment
Improved tolerability
Metabolic side effects
Neuropsychiatric side effects

This study investigated the safety and efficacy of switching HIV-positive adolescents from efavirenz to rilpivirine-based antiretroviral therapy, assessing both immunologic and virologic outcomes over 48 weeks.

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.
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

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