Efavirenz and chronic neuropsychiatric symptoms: a cross‐sectional case control study

Rihs, Tornia A.; Begley, Kim; Smith, Don; Sarangapany, J.; Callaghan, Alison; Kelly, Mónica; Post, Jeffrey J.; Gold, Jeffrey I.

doi:10.1111/j.1468-1293.2006.00419.x

Cited by 93 publications

(65 citation statements)

References 20 publications

(28 reference statements)

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“…Such side effects include dizziness, light-headedness, somnolence, insomnia, unusual dreams, amnesia, agitation, derealisation, depersonalization, hallucinations and euphoria, and typically begin after the first dose and usually resolve within 2-4 weeks of therapy or somewhat later. 94,98 In certain patients, some symptoms may not completely resolve and persisting CNS side effects have been reported. 98 Several other complications can occur during antiretroviral medication, for example metabolic and morphological changes such as lactic acidosis, lipoatrophy, fat accumulation and dyslipidaemia.…”

Section: Substance Use Disordersmentioning

confidence: 99%

“…94,98 In certain patients, some symptoms may not completely resolve and persisting CNS side effects have been reported. 98 Several other complications can occur during antiretroviral medication, for example metabolic and morphological changes such as lactic acidosis, lipoatrophy, fat accumulation and dyslipidaemia. 96 The immune reconstitution inflammatory syndrome (IRIS) is a spectrum of clinical signs and symptoms resulting from the restored ability to amount an inflammatory response associated with immune recovery.…”

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confidence: 99%

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HIV infection and psychiatric illness

Owe‐Larsson

Säll²,

Salamon³

et al. 2009

Afr. J. Psych

139

125

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Introduction HIV is a ribonucleic acid (RNA) retrovirus that is the causative agent for AIDS. HIV belongs to the Lentivirus genus in the family Retroviridae, characterized by a replication cycle in which the viral RNA is reverse transcribed into a DNA proviral form that is integrated into the host cell genome. The retrovirus is composed of two copies of single-stranded RNA that codes for the virus's 9 genes. The RNA is non-covalently linked to the core proteins, which in turn is surrounded by a viral envelope, which enables the virus to enter cells by binding to a specific cellular receptor located on the surface of cluster of differentiation 4 (CD4) cells. 1 A few years after the discovery of HIV-1, a second virus, HIV-2, was found in West Africa. HIV-1 and HIV-2 differ regarding their content of the genome, resulting in lower AIDS rates in HIV-2 infected individuals. 2 Once exposed to the body, the HIV virus antibodies may be detected after an acute flu-like illness, and then proceeds to infect specific cells of the immune system during an asymptomatic period that may last for years. In order to enter a cell, HIV must bind to CD4, typically found on T lymphocytes, blood monocytes, macrophages and some dendrite cells, and subsequently to one or a combination of several possible chemokine co-receptors, usually CCR5 and CXCR4. 3,4 The late HIV infection and psychiatric illness B Owe-Larsson, L Säll, E Salamon, C Allgulander Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry at Karolinska University Hospital Huddinge, Stockholm, Sweden Abstract Objective: To review the clinical features and current knowledge on the treatment of psychiatric symptoms and disorders in patients with human immunodeficiency virus (HIV) infection. Method: We searched the PubMed database combining HIV/AIDS with different keywords for psychiatric diagnoses and symptoms (e.g. depression, mania, anxiety, psychosis, dementia, substance abuse) and for psychopharmacological treatment. The years covered by these searches included 1980 to 2008. Results: Patients with HIV infection are at an increased risk of psychiatric illness. Major depressive disorder and subsyndromal depressive symptoms, as well as anxiety disorder and substance abuse are more prevalent among HIV infected individuals than among the general population. HIV-associated neurocognitive disorders (HAND) are common among HIV patients, and HIV-associated dementia (HAD) is a serious condition during the acquired immune deficiency syndrome (AIDS) stage of HIV disease. Secondary mania and psychosis might be the first clinical symptom of HIV dementia. The introduction of highly active anti-retroviral therapy (HAART) has resulted in significant decreases in morbidity and mortality for HIV infected patients. HAART has also decreased the incidence of HAD, but does not give complete protection from this condition. The utility of psychotropic medications in HIV patients has not been studied sufficiently as a basis for guidelines, and more controlled trials are n...

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Section: Substance Use Disordersmentioning

confidence: 99%

mentioning

confidence: 99%

HIV infection and psychiatric illness

Owe‐Larsson

Säll²,

Salamon³

et al. 2009

Afr. J. Psych

139

125

View full text Add to dashboard Cite

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“…Therefore, the reported prevalence is extremely variable depending upon the study and criteria used for diagnosis (15 to 50%) (1,2). Several models for the pathogenesis of HAND/MCMD arising during HAART treatment have been suggested, such as incomplete suppression of viral replication in the brain due to poor penetration of drugs to the central nervous system (CNS) (3)(4)(5), effects of aging on the brain (6)(7)(8), and CNS toxicity of long-term application of antiretroviral therapy (ART) (9,10), but the driving mechanism(s) of progression to HAND during HAART has not yet been determined.…”

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confidence: 99%

Laser Capture Microdissection Assessment of Virus Compartmentalization in the Central Nervous Systems of Macaques Infected with Neurovirulent Simian Immunodeficiency Virus

Matsuda

Brown

Foley

et al. 2013

J Virol

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bNonhuman primate-simian immunodeficiency virus (SIV) models are powerful tools for studying the pathogenesis of human immunodeficiency virus type 1 (HIV-1) in the brain. Our laboratory recently isolated a neuropathogenic viral swarm, SIVsmH804E, a derivative of SIVsmE543-3, which was the result of sequential intravenous passages of viruses isolated from the brains of rhesus macaques with SIV encephalitis. Animals infected with SIVsmH804E or its precursor (SIVsmH783Br) developed SIV meningitis and/or encephalitis at high frequencies. Since we observed macaques with a combination of meningitis and encephalitis, as well as animals in which meningitis or encephalitis was the dominant component, we hypothesized that distinct mechanisms could be driving the two pathological states. Therefore, we assessed viral populations in the meninges and the brain parenchyma by laser capture microdissection. Viral RNAs were isolated from representative areas of the meninges, brain parenchyma, terminal plasma, and cerebrospinal fluid (CSF) and from the inoculum, and the SIV envelope fragment was amplified by PCR. Phylogenetic analysis of envelope sequences from the conventional progressors revealed compartmentalization of viral populations between the meninges and the parenchyma. In one of these animals, viral populations in meninges were closely related to those from CSF and shared signature truncations in the cytoplasmic domain of gp41, consistent with a common origin. Apart from magnetic resonance imaging (MRI) and positron-emission tomography (PET) imaging, CSF is the most accessible assess to the central nervous system for HIV-1-infected patients. However, our results suggest that the virus in the CSF may not always be representative of viral populations in the brain and that caution should be applied in extrapolating between the properties of viruses in these two compartments.

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“…More concerning psychiatric complications such as severe depression and suicidal ideation may rarely occur, particularly in patients with pre-existing psychiatric disorders and substance abuse problems. 4,41,42 Genetic polymorphisms in CYP2B6, found more frequently in African-Americans, can lead to higher EFV concentrations and may explain higher rates of neurologic side effects. 43 In some studies, women may be more likely to discontinue EFV due to CNS toxicity, perhaps related to drug levels.…”

Section: Adverse Effects and Prescribing Considerationsmentioning

confidence: 99%

Issues in resistance, adherence, and comparative efficacy of the single-tablet regimen combination of tenofovir, emtricitabine, and efavirenz in the management of HIV-1 infection

Rebick¹,

Walmsley²

2012

VAAT

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Abstract:Atripla is the first once-daily, single-tablet, triple-combination antiretroviral therapy. It is recommended for the initial treatment of the naïve patient with human immunodeficiency virus-1 (HIV-1) infection in all current guidelines, based on its proven efficacy in numerous head-to-head randomized clinical trials. Not only has it proven efficacy, but the fixed-dose combination, Atripla, has resulted in an improvement in adherence, quality of life, and satisfaction among naïve as well as virally suppressed patients switching from another regimen. Despite the advantages, tolerability issues can arise that are related primarily to the efavirenz component, which is known to cause central nervous side effects such as dizziness, abnormal dreams, and anxiety. Although generally self-limited, these side-effects can lead to treatment discontinuation in the short-or long-term. Based on the observation of neural tube defects in macaque models, and isolated case reports in human fetuses with first trimester exposure, it is rated as Food and Drug Administration pregnancy category D, and considered as contraindicated in the first trimester of pregnancy where alternatives are available. Given the low genetic barrier of each of the individual components, resistance remains an important issue for patients with poor adherence, but is balanced in part by the long half-life of the drugs. Transmitted resistance is described in up to 16% of newly infected patients in population surveys, and is particularly prevalent in men who have sex with men. Minority variants that may impart resistant to efavirenz are not detected with currently used HIV-1 genotype assays, but nonetheless may also be implicated in patients who fail initial treatment. Several single-tablet regimens are recently licensed or in development that will challenge Atripla as the single-tablet first-line option, but none have shown superior efficacy to date.

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Efavirenz and chronic neuropsychiatric symptoms: a cross‐sectional case control study

Cited by 93 publications

References 20 publications

HIV infection and psychiatric illness

HIV infection and psychiatric illness

Laser Capture Microdissection Assessment of Virus Compartmentalization in the Central Nervous Systems of Macaques Infected with Neurovirulent Simian Immunodeficiency Virus

Issues in resistance, adherence, and comparative efficacy of the single-tablet regimen combination of tenofovir, emtricitabine, and efavirenz in the management of HIV-1 infection

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