Efavirenz therapeutic range in HIV-1 treatment-naive participants

AIDS Clinical Trials Group Study A5202 Team

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: 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 ARVnaive patients. A mid-dosing interval therapeutic range between 1000 and 4000 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 (1000-4000 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.

Original languageEnglish (US)
Pages (from-to)596-603
Number of pages8
JournalTherapeutic Drug Monitoring
Volume39
Issue number6
DOIs
StatePublished - Jan 1 2017

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efavirenz
HIV-1
Weights and Measures
Therapeutics
United States Dept. of Health and Human Services
Reverse Transcriptase Inhibitors

Keywords

  • Efavirenz
  • Therapeutic drug monitoring
  • Therapeutic range
  • Virologic failure

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Efavirenz therapeutic range in HIV-1 treatment-naive participants. / AIDS Clinical Trials Group Study A5202 Team.

In: Therapeutic Drug Monitoring, Vol. 39, No. 6, 01.01.2017, p. 596-603.

Research output: Contribution to journalArticle

AIDS Clinical Trials Group Study A5202 Team. / Efavirenz therapeutic range in HIV-1 treatment-naive participants. In: Therapeutic Drug Monitoring. 2017 ; Vol. 39, No. 6. pp. 596-603.
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keywords = "Efavirenz, Therapeutic drug monitoring, Therapeutic range, Virologic failure",
author = "{AIDS Clinical Trials Group Study A5202 Team} and Bednasz, {Cindy J.} and Venuto, {Charles S.} and Qing Ma and Daar, {Eric S.} and Sax, {Paul E.} and Fischl, {Margaret A} and Collier, {Ann C.} and Smith, {Kimberly Y.} and Camlin Tierney and Yang Yang and Wilding, {Gregory E.} and Morse, {Gene D.} and Hector Bolivar and Sandra Navarro and Koletar, {Susan L.} and Diane Gochnour and Edward Seefried and Julie Hoffman and Judith Feinberg and Michelle Saemann and Kristine Patterson and Donna Pittard and David Currin and Kerry Upton and Michael Saag and Graham Ray and Steven Johnson and Bartolo Santos and Funk, {Connie A.} and Michael Morgan and Brenda Jackson and Pablo Tebas and Aleshia Thomas and Kim, {Ge Youl} and Klebert, {Michael K.} and Santana, {Jorge L.} and Santiago Marrero and Jane Norris and Sandra Valle and Cox, {Gary Matthew} and Martha Silberman and Sadia Shaik and Ruben Lopez and Margie Vasquez and Demetre Daskalakis and Christina Megill and Todd Stroberg and Jessica Shore and Babafemi Taiwo and Mitchell Goldman",
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T1 - Efavirenz therapeutic range in HIV-1 treatment-naive participants

AU - AIDS Clinical Trials Group Study A5202 Team

AU - Bednasz, Cindy J.

AU - Venuto, Charles S.

AU - Ma, Qing

AU - Daar, Eric S.

AU - Sax, Paul E.

AU - Fischl, Margaret A

AU - Collier, Ann C.

AU - Smith, Kimberly Y.

AU - Tierney, Camlin

AU - Yang, Yang

AU - Wilding, Gregory E.

AU - Morse, Gene D.

AU - Bolivar, Hector

AU - Navarro, Sandra

AU - Koletar, Susan L.

AU - Gochnour, Diane

AU - Seefried, Edward

AU - Hoffman, Julie

AU - Feinberg, Judith

AU - Saemann, Michelle

AU - Patterson, Kristine

AU - Pittard, Donna

AU - Currin, David

AU - Upton, Kerry

AU - Saag, Michael

AU - Ray, Graham

AU - Johnson, Steven

AU - Santos, Bartolo

AU - Funk, Connie A.

AU - Morgan, Michael

AU - Jackson, Brenda

AU - Tebas, Pablo

AU - Thomas, Aleshia

AU - Kim, Ge Youl

AU - Klebert, Michael K.

AU - Santana, Jorge L.

AU - Marrero, Santiago

AU - Norris, Jane

AU - Valle, Sandra

AU - Cox, Gary Matthew

AU - Silberman, Martha

AU - Shaik, Sadia

AU - Lopez, Ruben

AU - Vasquez, Margie

AU - Daskalakis, Demetre

AU - Megill, Christina

AU - Stroberg, Todd

AU - Shore, Jessica

AU - Taiwo, Babafemi

AU - Goldman, Mitchell

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: 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 ARVnaive patients. A mid-dosing interval therapeutic range between 1000 and 4000 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 (1000-4000 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.

AB - Background: 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 ARVnaive patients. A mid-dosing interval therapeutic range between 1000 and 4000 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 (1000-4000 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.

KW - Efavirenz

KW - Therapeutic drug monitoring

KW - Therapeutic range

KW - Virologic failure

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