| Author | Luetkemeyer, Anne F. | |
| Author | Rosenkranz, Susan L. | |
| Author | Lu, Darlene | |
| Author | Marzan, Florence | |
| Author | Ive, Prudence | |
| Author | Hogg, Evelyn | |
| Author | Swindells, Susan | |
| Author | Benson, Constance A. | |
| Author | Grinsztejn, Beatriz | |
| Author | Sanne, Ian M. | |
| Author | Havlir, Diane V. | |
| Author | Aweeka, Francesca | |
| Author | Adult AIDS Clinical Trials Group A5221 Study Team | |
| Access date | 2018-11-05T16:33:39Z | |
| Available date | 2018-11-05T16:33:39Z | |
| Document date | 2013 | |
| Citation | LUETKEMEYER, Anne F. et al. 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. Clinical infectious diseases, v. 57, n. 4, p. 586-593, 2013. | pt_BR |
| ISSN | 1058-4838 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/29851 | |
| Language | eng | pt_BR |
| Rights | restricted access | pt_BR |
| Title | 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 | pt_BR |
| Type | Article | |
| DOI | 10.1093/cid/cit246 | |
| 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. | pt_BR |
| Affilliation | University of California. San Francisco General Hospital. HIV/AIDS Division. USA. | pt_BR |
| Affilliation | Harvard School of Public Health. Center for Biostatistics in AIDS Research. Boston, Massachusetts, USA. | pt_BR |
| Affilliation | Harvard School of Public Health. Center for Biostatistics in AIDS Research. Boston, Massachusetts, USA. | pt_BR |
| Affilliation | University of California. Department of Clinical Pharmacy. San Francisco, USA. | pt_BR |
| Affilliation | University of the Witwatersrand. Faculty of Health Sciences. Johannesburg, South Africa. | pt_BR |
| Affilliation | Social & Scientific Systems, Inc. Silver Spring, Maryland, USA. | pt_BR |
| Affilliation | University of Nebraska. Division of Infectious Diseases. Omaha, USA. | pt_BR |
| Affilliation | University of California. Antiviral Research Center. San Diego, USA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | University of the Witwatersrand. Faculty of Health Sciences. Johannesburg, South Africa. | pt_BR |
| Affilliation | University of California. San Francisco General Hospital. HIV/AIDS Division. USA. | pt_BR |
| Affilliation | University of California. Department of Clinical Pharmacy. San Francisco, USA. | pt_BR |
| Subject | HIV/AIDS | pt_BR |
| Subject | Efavirenz | pt_BR |
| Subject | Pharmacokinetics | pt_BR |
| Subject | Rifampin | pt_BR |
| Subject | Tuberculosis | pt_BR |
| Embargo date | 2023-01-01 | |
