ABCB1 variation and treatment response in AIDS patients: initial results of the Henan cohort.
HIV/AIDS has the highest mortality among infectious diseases in China. In ongoing efforts to alleviate this crisis, the national government has placed great emphasis on efforts in Henan province where HIV-infected former plasma donors in the 1990s contributed to AIDS becoming a public health crisis. Concomitant with a national initiative focusing the use of pharmacogenetics for the better prediction of treatment response, we studied genetic variants with known pharmacokinetic phenotypes in a set of 298 HAART-treated (highly active antiretroviral therapy) patients infected with HIV from the Henan cohort. We measured the association of response to treatment, assessed as changes in CD4+ T cell counts after antiretroviral therapy, of five polymorphisms in four genes (CYP2B6, ABCB1/MDR1, ABCG2, and ABCC4) in which variation has been suggested to affect the pharmacokinetics of drugs commonly employed to treat HIV/AIDS. We show that genotyping for ABCB1 variations (rs1045642 and rs2032582) may help predict HIV treatment response. We found variations in this gene have a significant association with outcome as measured by CD4+ T cell counts in a discovery subset (N= 197; odds ratio (OR) = 1.58; 95% CI 1.02-2.45), these results were confirmed in a validation subset of the cohort (N = 78; OR= 2.81; 95% CI 1.32-5.96). Exploratory analysis suggests that this effect may be specific to NVP (nevirapine) or 3TC (lamivudine) response. This publication represents the first genetic analysis in a continuing effort to study and assist the patients in a very large, unique, and historically significant HIV-AIDS cohort. Genotyping of AIDS patients for ABCB1 variation may help predict outcome and potentially could help guide treatment strategies.
Key Laboratory of Molecular Biophysics of Ministry of Education, Huazhong University of Science and Technology, Wuhan, China.
Peng
P
Zhu
Qian
Q
Zhu
Yilei
Y
Zhang
Xuejun
X
Ma
Zizhao
Z
Li
Jie
J
Li
Jiazhong
J
Chen
Le
L
Luo
Huijun Z
HZ
Ring
Brian Z
BZ
Ring
Li
L
Su
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002681:China; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1