Plasma concentrations of efavirenz are associated with body weight in HIV-positive individuals

Poeta, Júlia; Linden, Rafael; Antunes, Marina Venzon; Real, Lucia Helena Gonzales; Menezes, Andréia Magalhães de; Ribeiro, Jorge Pinto; Sprinz, Eduardo

doi:10.1093/jac/dkr360

Cited by 32 publications

(32 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Plasma concentration average of our population was 6,360 µg/L ± 539 µg/L. It is definitely higher than those found by Poeta and Wyen, which were respectively 2,200 and 2,077µg/L [15][16]. In the studies preceding ours, plasma concentrations averages were included in the therapeutic index described [1,000-4,000 µg/L].…”

Section: Efavirenz Plasma Concentrationscontrasting

confidence: 52%

“…Stohr et al had found that a high weight induced a weak plasmatic concentration of EFV [5]. Brazilian study of Poeta et al [15] in 2011 had also revealed that high BMI induced weak level concentration of EFV (p = 0.001) [15]. Also, high BMI can mean a great drug distribution volume and thus, low plasma concentration.…”

Section: Plasma Concentrations and Socio-demographic Factorsmentioning

confidence: 99%

See 1 more Smart Citation

Over Exposure to Efavirenz Plasma Concentrations among Beninese HIV Patients Treated by A 600 mg Daily Dose

Constant¹,

Mikal²,

Marcel³

et al. 2017

JPP

View full text Add to dashboard Cite

Therapeutic plasma concentrations of EFV (efavirenz) are between 1,000 ng/mL and 4,000 ng/mL. Concentrations below 1000 ng/mL are associated with higher risk of treatment failure, and concentrations above 4,000 ng/mL are associated with toxicity. The aim of the study was to appreciate EFV plasmas concentrations profile and the association between plasma levels and various characteristics in Beninese patients treated by a 600 mg standard daily-dose. Blood samples were collected and EFV plasma levels were measured by liquid chromatography coupled with mass spectrometry detection in HIV-infected patients receiving EFV in combination with other antiretroviral drugs for at least 14 days. Adverse effects occurring during treatment were collected through a questionnaire. An over-exposure to EFV among Beninese HIV patients were observed, with 46.4% of patients presenting EFV concentration above 4,000 ng/mL, although adverse effects were tolerated indicating that antiretroviral treatment is safe. The measurement of plasma concentration at the steady-state could contribute to early detection of treatment failure and adapt treatment in subjects presenting serious adverse effects within context of therapeutic drug monitoring.

show abstract

Section: Efavirenz Plasma Concentrationscontrasting

confidence: 52%

Section: Plasma Concentrations and Socio-demographic Factorsmentioning

confidence: 99%

Over Exposure to Efavirenz Plasma Concentrations among Beninese HIV Patients Treated by A 600 mg Daily Dose

Constant¹,

Mikal²,

Marcel³

et al. 2017

JPP

View full text Add to dashboard Cite

show abstract

“…Several studies have demonstrated that a higher weight were associated with lower efavirenz levels [5], [6], but how to adjust doses according to the weight remains a debatable issue. Some studies suggested an increase of efavirenz dose for heavy patients taking rifampicin [26], while other studies showed data arguing against this suggestion [10], [27].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Drug Monitoring and Pharmacogenetic Study of HIV-Infected Ethnic Chinese Receiving Efavirenz-Containing Antiretroviral Therapy with or without Rifampicin-Based Anti-Tuberculous Therapy

et al. 2014

View full text Add to dashboard Cite

ObjectivesPlasma efavirenz concentrations in HIV-infected patients with tuberculosis (TB) may be affected by cytochrome P450 (CYP) 2B6 single-nucleotide polymorphisms and concurrent rifampicin use. We aimed to investigate the effects of CYP2B6 G516T polymorphisms and concomitant rifampicin use on the plasma efavirenz concentrations in HIV-infected Taiwanese.MethodsHIV-infected patients with or without TB who had received combination antiretroviral therapy containing efavirenz (600 mg daily) for two weeks or greater were enrolled for determinations of CYP2B6 G516T polymorphism and plasma efavirenz concentrations with the use of polymerase-chain-reaction restriction fragment-length polymorphism and high-performance liquid chromatography, respectively.ResultsFrom October 2009 to August 2012, 171 HIV-infected patients, including 18 with TB, were enrolled 113 (66.1%) with CYP2B6 G516G, 55 (32.2%) GT, and 3 (1.8%) TT genotype. Patients receiving rifampicin had a significantly lower median plasma efavirenz concentration than the control group (2.16 vs 2.92 mg/L, P = 0.003); however, all patients achieved target plasma concentration (>1 mg/L). Patients with GT or TT genotype had a significantly higher plasma concentration than those with GG genotype (2.50 vs 3.47 mg/L for GT genotype and 8.78 mg/L for TT genotype, P<0.001). Plasma efavirenz concentration >4 mg/L was noted in 38 (22.2%) patients, which was associated with a lower weight (per 10-kg increase, odds ratio, 0.52; 95% confidence interval, 0.33–0.83) and GT or TT genotype (odds ratio, 4.35; 95% confidence interval, 1.97–9.59) in multivariate analysis.ConclusionsDespite combination with rifampicin, sufficient plasma efavirenz concentrations can be achieved in HIV-infected Taiwanese with TB who receive efavirenz 600 mg daily. Carriage of CYP2B6 516 GT and TT genotypes and a lower weight are associated with higher plasma efavirenz concentrations.

show abstract

“…However, multivariate analysis (n = 41) indicated that efavirenz concentrations show a significant (p = 0.015) inverse relationship with body weight through. 21 …”

Section: Discussionmentioning

confidence: 99%

Efavirenz Therapeutic Range in HIV-1 Treatment-Naive Participants

Bednasz

Venuto

et al. 2017

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

Objectives Efavirenz is currently suggested as an alternative to recommended antiretroviral (ARV) regimens by the Department of Health and Human Services for the treatment of HIV-1 in ARV-naive patients. A mid-dosing interval therapeutic range between 1,000 and 4,000 ng/mL for efavirenz has been proposed in the literature, with patients more likely to experience virologic failure below this range and adverse effects above. The current study reports an analysis of virologic outcome between those above, below, or within the reported efavirenz therapeutic range (1,000–4,000 ng/mL) and within subgroups. Methods This analysis examined efavirenz plasma concentrations obtained from participants enrolled in AIDS Clinical Trials Group Study A5202. This investigation divided subjects into those who experienced virologic failure and those who did not. These subjects were further separated to investigate those who had “high,” “within,” or “low” plasma concentrations, based on the therapeutic range. The association between virologic failure and plasma concentration was statistically examined in addition to the variables race/ethnicity, sex, assigned nucleos(t)ide reverse transcriptase inhibitor backbone, age at study entry, history of intravenous drug use, weight, and screening HIV-1 RNA stratification level. Results In univariate analyses, a statistically significant difference was found when comparing the efavirenz concentration groups, (22 failures among the “low” concentration group [19%], 65 failures among the “within” concentration group [12%], and 11 failures among the “high” concentration group [9%]) when evaluating virologic failure as an outcome (p = 0.04). In addition, the proportion of participants with virologic failure differed across race/ethnicity groups (p = 0.03) with black non-Hispanic participants observed to have the highest rate (17%). Efavirenz concentration group, race/ethnicity, age, weight, and the interaction between efavirenz concentration group and weight were found to be significantly associated with virologic failure in multivariable logistic regression analysis. Conclusions The proposed efavirenz therapeutic range, combined with the impact of a patient’s weight, is associated with virologic failure in HIV-infected ARV-naive individuals in the United States. Additional analysis is recommended to determine the most appropriate concentration value that defines the lower limit of the efavirenz therapeutic range.

show abstract

Plasma concentrations of efavirenz are associated with body weight in HIV-positive individuals

Cited by 32 publications

References 9 publications

Over Exposure to Efavirenz Plasma Concentrations among Beninese HIV Patients Treated by A 600 mg Daily Dose

Over Exposure to Efavirenz Plasma Concentrations among Beninese HIV Patients Treated by A 600 mg Daily Dose

Therapeutic Drug Monitoring and Pharmacogenetic Study of HIV-Infected Ethnic Chinese Receiving Efavirenz-Containing Antiretroviral Therapy with or without Rifampicin-Based Anti-Tuberculous Therapy

Efavirenz Therapeutic Range in HIV-1 Treatment-Naive Participants

Contact Info

Product

Resources

About