O'Neil WM, Tsoukas CM, Gilfix BM, Wainer IW; International Conference on AIDS.
Int Conf AIDS. 1996 Jul 7-12; 11: 451 (abstract no. Pub.B.1081).
McGill University, Dept. of Medicine, Division of Experimental Medicine, Montreal General Hospital, Quebec, Canada. Fax: 934-8214. E-mail: BS41@musicb.mcgill.ca.
The N-acetyltransferase (NAT2) phenotype (slow vs. fast) was assessed in a group of HIV+/AIDS patients using caffeine as the probe drug. The 4-h urinary ratio of AFMU/1-methylxanthine was measured by capillary electrophoresis in 67 patients aged 26 to 74 (45 plus or minus 11, 9 female, 58 male) whose CD4+ cell count ranged from 2 to 551 mm-3 (191 plus or minus 108).A slow NAT2 phenotype has been implicated as a risk factor for hypersensitivity to TMP-SMX despite SMX's far greater affinity for NAT1 than NAT2. Studies of NAT2 phenotype in AIDS show an abnormal distribution of slow metabolizers (93% of acutely ill patients) vs. 56% in healthy HIV+ patients, 55% among seronegatives. The distribution of the genotype among AIDS patients, however, has proven to be normal (55% slow). No study has yet examined both the phenotype and genotype in the same cohort of patients, nor have any longitudinal studies been undertaken.We have initiated a longitudinal study of the effect of AIDS-related disease progression on NAT2 activity in which both geno- and phenotype are being examined. Initial results of 67 patients will be reported. The data indicate a correlation between % difference from ideal body weight (IBW) and slow phenotype: 86% of subjects who were greater than or equal to 10% underweight were slow acetylators vs. those who were either plus or minus 10% of IBW or greater than or equal to 110% of IBW, (60 and 67% respectively). Body mass index (BMI) showed a similar correlation: 88% of subjects whose BMI was less than 21 were slow metabolizers while only 61% of those having a BMI greater than 21 were slow. Neither CD4+ count nor antiretroviral therapy appeared to correlate.It was also observed that patients who had discontinued TMP-SMX due to adverse reactions were no more likely to be slow acetylators (73% incidence) than those who had never tried the drug (76% slow). Compare these data to the incidence of slow phenotype overall in the 67 subjects (69%) and in those on TMP-SMX at the time of testing (53%). This lack of correlation with TMP-SMX sensitivity is at odds with the literature but not with the hypothesis that phenotype can change with disease state. Five study participants have been phenotyped on 2 occasions: "flips" of phenotype from fast to slow (1 patient) as well as from slow to fast (1 patient) were observed.
Publication Types:
Keywords:
- AIDS Vaccines
- Acetyltransferases
- Acquired Immunodeficiency Syndrome
- Arylamine N-Acetyltransferase
- CD4 Lymphocyte Count
- Caffeine
- Female
- Genotype
- HIV Infections
- HIV Seropositivity
- Humans
- Incidence
- Longitudinal Studies
- Male
- NAT2 protein, human
- Phenotype
- Risk Factors
- Trimethoprim-Sulfamethoxazole Combination
- genetics
Other ID:
UI: 102221428
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