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.
Author(s): Wohl DA(1), Dumond JB, Blevins S, Pittard D, Ragan D, Wang R, Massengale K, Walsh
K, Floris-Moore M, Eron JJ Jr, Richardson A, Hudgens MG, Kashuba AD.
Affiliation(s): Author information:
(1)The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,
USA. wohl@med.unc.edu
Publication date & source: 2013, Antimicrob Agents Chemother. , 57(2):784-8
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.
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