Relationship between weight, efavirenz exposure, and virologic suppression in HIV-infected patients on rifampin-based tuberculosis treatment in the AIDS Clinical Trials Group A5221 STRIDE Study.

TitleRelationship between weight, efavirenz exposure, and virologic suppression in HIV-infected patients on rifampin-based tuberculosis treatment in the AIDS Clinical Trials Group A5221 STRIDE Study.
Publication TypeJournal Article
Year of Publication2013
AuthorsLuetkemeyer AF, Rosenkranz SL, Lu D, Marzan F, Ive P, Hogg E, Swindells S, Benson CA, Grinsztejn B, Sanne IM, Havlir DV, Aweeka F
Corporate AuthorsAdult AIDS Clinical Trials Group A5221 Study Team
JournalClin Infect Dis
Volume57
Issue4
Pagination586-93
Date Published2013 Aug
ISSN1537-6591
KeywordsAdult, Anti-HIV Agents, Antitubercular Agents, Benzoxazines, Body Weight, Drug Interactions, Female, HIV Infections, Humans, Male, Rifampin, Treatment Outcome, Tuberculosis, Viral Load
Abstract

BACKGROUND: Rifampin (RIF) upregulates CYP 450 isoenzymes, potentially lowering efavirenz (EFV) exposure. The US EFV package insert recommends an EFV dose increase for patients on RIF weighing ≥50 kg. We conducted a pharmacokinetic study to evaluate EFV trough concentrations (Cmin) and human immunodeficiency virus (HIV) virologic suppression in patients on EFV (600 mg) and RIF-based tuberculosis treatment in the multicenter randomized trial (ACTG A5221).

METHODS: EFV Cmin was measured 20-28 hours post-EFV dose at weeks 4, 8, 16, 24 on-RIF and weeks 4, 8 off-RIF. Results were evaluated with 2-sided Wilcoxon rank-sum, χ(2), Fisher exact tests and logistic regression (5% type I error rate).

RESULTS: Seven hundred eighty patients received EFV; 543 provided ≥1 EFV Cmin. Median weight was 52.8 kg (interquartile range [IQR], 48.0-59.5), body mass index 19.4 kg/m(2) (IQR, 17.5-21.6), and age 34 years (IQR, 29-41); 63% were male, 74% black. Median Cmin was 1.96 µg/mL on-RIF versus 1.80 off-RIF (P = .067). Cmin were significantly higher on-RIF versus off-RIF in blacks (2.08 vs 1.75, P = .005). Weight ≥60 kg on-RIF, compared to <60 kg, was associated with lower EFV Cmin (1.68 vs 2.02, P = .021). However, weight ≥60 kg was associated with more frequent HIV RNA < 400 copies/mL at week 48, compared to weight <60 kg (81.9% vs 73.8%, P = .023).

CONCLUSIONS: EFV and RIF-based tuberculosis therapy coadministration was associated with a trend toward higher, not lower, EFV Cmin compared to EFV alone. Patients weighing ≥60 kg had lower median EFV Cmin versus those <60 kg, but there was no association of higher weight with reduced virologic suppression. These data do not support weight-based dosing of EFV with RIF.

DOI10.1093/cid/cit246
Alternate JournalClin. Infect. Dis.
PubMed ID23592830
PubMed Central IDPMC3719885
Grant ListP30 AI027763 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069399 / AI / NIAID NIH HHS / United States
UM1 AI069463 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States