LOW SERUM THIOL LEVELS PREDICT SHORTER TIMES-TO-DEATH AMONG HIV-INFECTED INJECTING DRUG-USERS

Objectives: To investigate whether serum thiol levels are altered by H IV disease, and whether low serum thiols predict time to death among H IV-infected injecting drug users (IDU). Design: A cross-sectional stud y of serum thiol levels among 13 HIV-seronegative IDU, 116 HIV-seropos itive IDU, and 17 HIV-seropositive IDU with a history of AIDS, and a c ohort study of the 133 HIV-infected IDU who took part in the cross-sec tional study. Methods: Subjects were recruited from a methadone-mainte nance treatment program during 1990-1991. Total serum thiols were dete rmined spectrophotometrically at enrolment; low serum thiols were defi ned as those with an absorbance at 412 nm less than or equal to 0.46. Deaths through 31 December 1993 were determined from the National Deat h Index (NDI). Twenty-six HIV-seropositive subjects died during follow up; death certificates, which were obtained for 23 subjects, indicate d AIDS or HIV infection for 20. Product-limit estimation was used to c alculate survival. Multivariate analyses employed Cox proportional-haz ards regression. Results: Analysis of cross-sectional data showed that serum thiols did not differ significantly among HIV-free subjects, HI V-infected subjects, and HIV-infected subjects with a history of AIDS. Cohort analysis, adjusted for age, revealed that persons with low ser um thiols had a significantly increased hazard of death compared with those with high serum thiols (relative hazard = 2.83; 95% confidence i nterval (CI), 1.15, 6.97); a significant interaction between low serum thiols and a history of AIDS was associated with a relative hazard of 5.65 (95% CI, 1.22, 26.1). Conclusions: Among HIV-infected persons, l ow serum thiols, especially in concert with a history of AIDS, predict mortality risk. These findings support the hypothesis that oxidative stress is critical to the pathogenesis of HIV infection.