N-ACETYLATION AMONG HIV-POSITIVE PATIENTS AND PATIENTS WITH AIDS - WHEN IS FAST, FAST AND SLOW, SLOW

Background: The discrepancy between genotype and expressed phenotype o f the polymorphic N-acetyltransferase (NAT2) has been suggested by sep arate genotypic and phenotypic studies in populations with human immun odeficiency virus (HIV). Only one study has examined both genotype and phenotype in the same population, and no discrepancies were observed. Methods: In a cross-sectional study, 105 HIV-positive patients and pa tients with acquired immunodeficiency syndrome (AIDS) were phenotyped for NAT2 activity with use of caffeine as an in vivo probe; 50 of thes e patients were also genotyped by restriction mapping and allele-speci fic amplification, In a longitudinal study, 23 patients were phenotype d at least twice during the 2-year study,Results: The distribution of the NAT2 phenotype among the 105 patients was unimodal and skewed towa rd slow acetylators as opposed to the bimodal distribution observed in healthy white populations, The genotype distribution was 26:24 slow:f ast, There were 18 discrepancies between genotype and phenotype: 12 sl ow acetylators with fast genotypes and six fast acetylators with slow genotypes, No drug-related effects on NAT2 activity were apparent, but the role of disease progression was evident, Among the slow acetylato rs whose genotype was fast, the incidence of AIDS was higher (six of 1 2) than that among the fast acetylators whose genotype was fast (two o f 14), Among patients phenotyped more than once (mean time between sam ples, 10.4 months) changes in phenotype from fast to slow were associa ted with progression of HIV infection. Conclusions: Disease progressio n in HN infection and AIDS may alter expression of the NAT2 gene, The genotype and the phenotype are not interchangeable measurements, In th e HIV population, to know the genotype is useful only if the phenotype is also known and vice versa.