2006/08/15 by Kwok Lung Tong, Makiko Yoshida, Kazuhiro Shimasaku +10 · 4 citations
Medicine · Pharmacology, Toxicology and Pharmaceutics · Physics and Astronomy · #Astrophysics #Galaxies: Formation, Evolution, Phenomena #Galaxy #Hormonal and reproductive studies #Luminosity #Luminosity function #Optics #Pharmacogenetics and Drug Metabolism #Physics #Redshift #Ultraviolet #astro-ph
paper · pdf · doi:10.1086/508621
published as Astrophys.J.653:988-1003,2006 · 28 pages, 25 figures, accepted for publication in ApJ, a high resolution version of Figs.7,8,9 is available at http://hikari.astron.s.u-tokyo.ac.jp/~yoshida/sdflbglf/
openalex publication_date 2006/08/15 · arxiv created 2006/08/24 · arxiv updated 2009/12/01 · openalex created_date 2022/10/03 · openalex updated_date 2026/07/30
To the editor—The article by Ribaudo et al. [1] and the accompanying editorial commentary [2] have come at the right time to stimulate debates on how, with a global perspective, a treatment algorithm for HAART should be strategically developed to achieve maximum effectiveness. In the not-too-distant past, HAART was an expensive commodity of the Western world. With the expansion of treatment access, patients with HIV infection from varied ethnic origins are exposed to the same efficacious therapy, which is not without harmful consequences—toxicity and resistance emergence—if managed inappropriately. The poor metabolism of efavirenz, a once-daily nonnucleoside reverse-transcriptase inhibitor, in persons with the CYP2B6 G516T allele (also termed 2B6*6) is a case in point. The allelic frequency varies from 0.16 in the Japanese [3] and 0.14 in Koreans [4] to a much higher level of 0.42 in West Africans and 0.62 in Papua New Guineans [5], compared with an allelic frequency of 0.28 in white Americans. We set out to establish the allelic frequency in Chinese persons against the background of a rising number of patients with HIV who received a diagnosis in mainland China. Buffy coat specimens from 100 Chinese persons who donated blood were collected in October 2005 at the Hong Kong Red Cross Blood Transfusion Service. Direct sequencing was performed to screen for single-nucleotide polymorphisms, and restriction fragment–length polymorphism with the BsrI enzyme (New England Biolab) was used to confirm the G516 sequence. A total of 76 samples were successfully sequenced, yielding the following results: GG alleles in 28 samples, GT in 30 and TT in 18. The allelic frequency of G516T was high, at 0.43. What are the implications of ours and other groups' results in the diverse pattern of allelic frequency of G516T? Studies have confirmed the association of the specific allele with a higher plasma level of efavirenz and a longer elimination half-life on treatment cessation [1]. The former association predicts neurologic toxicity, and the latter means a higher inherent risk of resistance. Rather than interpersonal variation, the differences in immunogenetic and pharmacokinetic characteristics appear to be associated with ethnicity. Nolan et al. [2] proposed 3 scenarios in addressing the challenge. The first scenario would mean that many patients in populations where the 2B6*6 allele is prevalent would be exposed to efavirenz toxicity. The second and third scenarios would only be applicable in affluent societies where therapeutic drug monitoring and immunogenetic investigations can be offered for individual clinical indications. An alternative approach is urgently needed. Clinic-specific protocols should be developed that take into consideration the immunogenetic and pharmacokinetic characteristics of the respective population. Inexpensive laboratory investigations should be designed to help distinguish between high-risk and low-risk patients, with regard to their proneness to efavirenz-related complications. An allelic frequency of 0.4 or above in Chinese, West Africans, and Papua New Guineans is simply too high to be ignored. With time, it is possible that most patients who receive HAART will be from the developing world, where the immunogenetic and pharmacokinetic characteristics differ significantly from those in the Western world today. Financial support. Research Grant Council of Hong Kong Special Administrative Region Government (CUHK7334/03M, CUHK7394/04M to M.L.H.), and the South China National Research Centre for Integrated Biosciences (to H.F.K.), The Chinese University of Hong Kong. Potential conflicts of interest. All authors: no conflicts.