Use of Efavirenz Is Not Associated with a Higher Risk of Depressive Disorders: A Substudy of the Randomized Clinical Trial ALIZE-ANRS 099

Journot, Valérie; Chêne, Geneviève; Castro, Nathalie De; Rancinan, Corinne; Cassuto, Jill‐Patrice; Allard, Christian; Vildé, J. L.; Sobel, Alain; Garré, M; Molina, Jean‐Michel

doi:10.1086/504323

Cited by 45 publications

(29 citation statements)

References 25 publications

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“…The same study indicated that the 600-mg dose of EFV is associated with a high rate of adverse events that could lead to discontinuation, which suggests that the lower dose of 400 mg may be almost as effective without the high discontinuation rate. In the present study, associated with the dose-reduction regimen, a significant number of patients experienced improvement of CNS symptoms, which was unexpected on the basis of previous reports [5,21,22]. Interestingly, some of these patients did not appreciate their clinical state and considered themselves to have no CNS-related symptoms during the standard-dose treatment.…”

Section: Discussionsupporting

confidence: 76%

“…However, after the dose reduction, they reassessed the status and evaluated symptoms during the treatment with the standard dose as associated with CNS symptoms and indicated that the reduced dose of EFV relieved them of such symptoms. Because EFV-treated patients often stick to the regimen, previous reports of symptom questionnaires conducted during the standard treatment might have underestimated the EFV-associated CNS symptoms [5,21,22]. However, this finding might be confounded by placebo effect, because the patients were told that their EFV levels were high while receiving the initial dose and decreased throughout the dose-reduction protocol.…”

Section: Discussionmentioning

confidence: 99%

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Successful Efavirenz Dose Reduction in HIV Type 1-Infected Individuals with Cytochrome P450 2B6 6 and 26

Gatanaga

Hayashida

Tsuchiya

et al. 2007

Clinical Infectious Diseases

204

146

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Background. Efavirenz (EFV) is metabolized primarily by cytochrome P450 2B6 (CYP2B6), and high plasma concentrations of the drug are associated with a GrT polymorphism at position 516 (516GrT) of CYP2B6 and frequent central nervous system (CNS)-related side effects. Here, we tested the feasibility of genotype-based dose reduction of EFV.Methods. CYP2B6 genotypes were determined in 456 human immunodeficiency virus type 1 (HIV-1)-infected patients who were receiving EFV treatment or were scheduled to receive EFV-containing treatment. EFV dose was reduced in CYP2B6 516GrT carriers who had high plasma EFV concentrations while receiving the standard dosage (600 mg). EFV-naive homozygous CYP2B6 516GrT carriers were treated with low-dose EFV. In both groups, the dose was further reduced when plasma EFV concentration remained high.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Successful Efavirenz Dose Reduction in HIV Type 1-Infected Individuals with Cytochrome P450 2B6 6 and 26

Gatanaga

Hayashida

Tsuchiya

et al. 2007

Clinical Infectious Diseases

204

146

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“…Additionally, depression occurred at similar but low rates in both the RPV and EFV groups. Data from previous studies that evaluated depression in patients treated with EFV are conflicting, with some investigators reporting a link between increased depression and EFV [19,21,42], while others failed to find any such association [20,43,44]. Patients who discontinue highly active ARV therapy because of AEs do so mainly within the first few months following therapy initiation [3,45].…”

Section: Tolerability Of Rilpivirine Vs Efavirenz 395mentioning

confidence: 99%

Neurological and psychiatric tolerability of rilpivirine (TMC278) vs. efavirenz in treatment‐naïve, HIV‐1‐infected patients at 48 weeks

Mills¹,

Antinori

Clotet

et al. 2013

HIV Medicine

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ObjectivesThe aim of the study was to compare the neuropsychiatric safety and tolerability of rilpivirine (TMC278) vs. efavirenz in a preplanned pooled analysis of data from the ECHO and THRIVE studies which compared the safety and efficacy of the two drugs in HIV-1 infected treatment naïve adults. MethodsECHO and THRIVE were randomized, double-blind, double-dummy, 96-week, international, phase 3 trials comparing the efficacy, safety and tolerability of rilpivirine 25 mg vs. efavirenz 600 mg once daily in combination with two background nucleoside/tide reverse transcriptase inhibitors. Safety and tolerability analyses were conducted when all patients had received at least 48 weeks of treatment or discontinued earlier. Differences between treatments in the incidence of neurological and psychiatric adverse events (AEs) of interest were assessed in preplanned statistical analyses using Fisher's exact test. ResultsAt the time of the week 48 analysis, the cumulative incidences in the rilpivirine vs. efavirenz groups of any grade 2-4 treatment-related AEs and of discontinuation because of AEs were 16% vs. 31% (P < 0.0001) and 3% vs. 8% (P = 0.0005), respectively. The incidence of treatmentrelated neuropsychiatric AEs was 27% vs. 48%, respectively (P < 0.0001). The incidence of treatment-related neurological AEs of interest was 17% vs. 38% (P < 0.0001), and that of treatment-related psychiatric AEs of interest was 15% vs. 23% (P = 0.0002). Dizziness and abnormal dreams/nightmares occurred significantly less frequently with rilpivirine vs. efavirenz (P < 0.01). In both groups, patients with prior neuropsychiatric history tended to report more neuropsychiatric AEs but rates remained lower for rilpivirine than for efavirenz. ConclusionsRilpivirine was associated with fewer neurological and psychiatric AEs of interest than efavirenz over 48 weeks in treatment-naïve, HIV-1-infected adults. Under current guidelines, the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) is recommended as a preferred component of ARV regimens for treatment-naïve patients [11]. EFV has good overall tolerability but has been associated with some AE-related concerns, particularly neuropsychiatric symptoms that typically begin shortly after therapy initiation [12][13][14]. An analysis of four phase 2/3 controlled clinical trials has shown that 53% of EFV vs. 25% of control recipients reported central nervous system AEs (all grades) [1,3]. While EFV-associated neuropsychiatric AEs are often transient, symptoms such as abnormal dreams, dizziness, somatization, irritability and stress can persist in some instances for several months to years [15][16][17][18][19][20], and patients may experience symptoms of depression at any time during treatment [12,13].Several studies have compared the incidences of neuropsychiatric AEs with EFV-based vs. non-EFV-based ARV regimens [21][22][23][24]. Maintenance of virological control and significant improvement in neuropsychiatric AEs were demonstrated by switching from an EFV-to a nevirapinebase...

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“…12 Depressive disorders among PLHIV were also thought to be related to the use of the antiretroviral drug efavirenz, but this was disputed by a large study in 2005. 13 Optimal adherence to antiretroviral therapy (ART) is essential for viral suppression and positive treatment outcomes. 14 The negative impact of depressive disorders on adherence to ART has been demonstrated in developed countries.…”

Section: Introductionmentioning

confidence: 99%

The association between depression and adherence to antiretroviral therapy in HIV-positive patients, KwaZulu-Natal, South Africa

Kitshoff

Campbell

Naidoo

2012

South African Family Practice

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Use of Efavirenz Is Not Associated with a Higher Risk of Depressive Disorders: A Substudy of the Randomized Clinical Trial ALIZE-ANRS 099

Abstract: The frequency of depressive disorders was high in this population, but the disorders were not related to EFV treatment. Younger age and a history of depression are important determinants for depression and should be considered for early detection and case management.

Cited by 45 publications

References 25 publications

Successful Efavirenz Dose Reduction in HIV Type 1-Infected Individuals with Cytochrome P450 2B6 6 and 26

Successful Efavirenz Dose Reduction in HIV Type 1-Infected Individuals with Cytochrome P450 2B6 6 and 26

Neurological and psychiatric tolerability of rilpivirine (TMC278) vs. efavirenz in treatment‐naïve, HIV‐1‐infected patients at 48 weeks

The association between depression and adherence to antiretroviral therapy in HIV-positive patients, KwaZulu-Natal, South Africa

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Use of Efavirenz Is Not Associated with a Higher Risk of Depressive Disorders: A Substudy of the Randomized Clinical Trial ALIZE-ANRS 099

Abstract: The frequency of depressive disorders was high in this population, but the disorders were not related to EFV treatment. Younger age and a history of depression are important determinants for depression and should be considered for early detection and case management.

Cited by 45 publications

References 25 publications

Successful Efavirenz Dose Reduction in HIV Type 1-Infected Individuals with Cytochrome P450 2B6 *6 and *26

Successful Efavirenz Dose Reduction in HIV Type 1-Infected Individuals with Cytochrome P450 2B6 *6 and *26

Neurological and psychiatric tolerability of rilpivirine (TMC278) vs. efavirenz in treatment‐naïve, HIV‐1‐infected patients at 48 weeks

The association between depression and adherence to antiretroviral therapy in HIV-positive patients, KwaZulu-Natal, South Africa

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Product

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Successful Efavirenz Dose Reduction in HIV Type 1-Infected Individuals with Cytochrome P450 2B6 6 and 26

Successful Efavirenz Dose Reduction in HIV Type 1-Infected Individuals with Cytochrome P450 2B6 6 and 26