title: Raltegravir pharmacokinetics in treatment-naive patients is not influenced by race: results from the raltegravir early therapy in African-Americans living with HIV (REAL) study.
abstract: Racial differences in antiretroviral treatment responses remain incompletely explained and may be a consequence of differential pharmacokinetics (PK) associated with race. Raltegravir, an inhibitor of HIV-1 integrase, is commonly used in the treatment of HIV-infected patients, many of whom are African-American. However, there are few data regarding the PK of raltegravir in African-Americans. HIV-infected men and women, self-described as African-American and naive to antiretroviral therapy were treated with raltegravir (RAL) at 400 mg twice a day, plus a fixed dose of tenofovir-emtricitabine (TDF/FTC) at 300 mg/200 mg once daily. Intensive PK sampling was conducted over 24 h at week 4. Drug concentrations at two trough values of 12 and 24 h after dosing (C(12) and C(24)), area under the concentration-curve values (AUC), maximum drug concentration (C(max)), and the time at which this concentration occurred (T(max)) in plasma were estimated with noncompartmental pharmacokinetic methods and compared to data from a subset of white subjects randomized to the RAL twice a day (plus TDF/FTC) arm of the QDMRK study, a phase III study of the safety and efficacy of once daily versus twice daily RAL in treatment naive patients. A total of 38 African-American participants were enrolled (90% male) into the REAL cohort with the following median baseline characteristics: age of 36 years, body mass index (BMI) of 23 kg/m(2), and a CD4 cell count of 339/ml. Plasma HIV RNA levels were below 200 copies/ml in 95% of participants at week 4. The characteristics of the 16 white QDMRK study participants were similar, although fewer (69%) were male, the median age was higher (45 years), and BMI was lower (19 kg/m(2)). There was considerable interindividual variability in RAL concentrations in both cohorts. Median C(12) in REAL was 91 ng/ml (range, 10 to 1,386) and in QDMRK participants was 128 ng/ml (range, 15 to 1,074). The C(max) median concentration was 1,042 ng/ml (range, 196 to 10,092) for REAL and 1,360 ng/ml (range, 218 to 9,701) for QDMRK. There were no significant differences in any RAL PK parameter between these cohorts of African-American and white individuals. Based on plasma PK, and with similar adherence rates, the performance of RAL among HIV-infected African-Americans should be no different than that of infected patients who are white.
authors.affiliation: The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. wohl@med.unc.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Wohl
authors.forename: Julie B
authors.initials: JB
authors.lastname: Dumond
authors.forename: Suzanne
authors.initials: S
authors.lastname: Blevins
authors.forename: Donna
authors.initials: D
authors.lastname: Pittard
authors.forename: David
authors.initials: D
authors.lastname: Ragan
authors.forename: Ruili
authors.initials: R
authors.lastname: Wang
authors.forename: Kelley
authors.initials: K
authors.lastname: Massengale
authors.forename: Kendall
authors.initials: K
authors.lastname: Walsh
authors.forename: Michelle
authors.initials: M
authors.lastname: Floris-Moore
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.forename: Amy
authors.initials: A
authors.lastname: Richardson
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hudgens
authors.forename: Angela D M
authors.initials: AD
authors.lastname: Kashuba
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use; D000328:Adult; D001741:Black or African American; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use; D004334:Drug Administration Schedule; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000097:blood / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D044469:Racial Groups; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D019562:Viral Load; D044465:White People
chemical_list: D019428:HIV Integrase Inhibitors; D063065:Organophosphonates; D011760:Pyrrolidinones; D003841:Deoxycytidine; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D019427:HIV Integrase; D000068679:Emtricitabine; D000225:Adenine