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Objective: To determine the durability of zidovudine-induced delay in clinical progression of asymptomatic human immunodeficiency virus (HIV) disease and to assess the relationship between this effect and the entry CD4+ cell count.Design and Interventions: Extended follow-up data from subjects participating in protocol 019 of the AIDS [acquired immunodeficiency syndrome] Clinical Trials Group were examined. Subjects were offered a total daily dose of 500 mg of open-label zidovudine after the unblinding of the original randomized trial in 1989. Original treatment groups included placebo, 500 mg of zidovudine, or 1500 mg of zidovudine daily in divided doses. Three distinct analyses were conducted to assess the duration of zidovudine's effect on progression to AIDS or death: (1) analysis of all follow-up information from all subjects, (2) analysis of all subjects but with follow-up of original placebo-assigned subjects censored at the time open-label zidovudine was initiated, and (3) analysis of the effect of initiating zidovudine in subjects initially assigned to receive placebo.Setting: University-based and university-affiliated AIDS research clinics participating in AIDS Clinical Trials Group protocol 019.Patients: A total of 1565 asymptomatic HIV-infected subjects with entry CD4+ cell counts less than 0.50 x 10(9)/L (500/microL).Main Outcome Measure: Time to progression to AIDS or death.Results: During follow-up of up to 4.5 years (mean, 2.6 years), 232 subjects progressed to AIDS or died. In each of the three analyses described herein, zidovudine was associated with a significant (P = .008, .004, .007) decrease in the risk of such progression. However, each of these analyses also indicated a decreasing placebo:zidovudine relative risk with duration of use (P = .002, .08, .04), suggesting a nonpermanent effect. The duration of benefit appeared to be related to entry CD4+ cell count, with greater benefit in those with higher counts at entry. No significant differences in survival were found between those originally randomized to zidovudine or placebo.Conclusions: Zidovudine at 500 mg/d caused a significant delay in progression to AIDS or death, but its earlier use in asymptomatic disease was not associated with an additional prolongation of survival compared with delayed initiation. The delay in progression diminished over time especially in subjects with entry CD4+ cell counts less than 0.30 x 10(9)/L (300/microL). Treatment strategies that alter drug regimens before the loss of zidovudine benefit should be explored. [ABSTRACT FROM AUTHOR]

Vancomycin instilled in an Ommaya reservoir was used to treat a reservoir-associated infection. Vancomycin concentrations in cerebrospinal fluid (CSF) were measured, and derivation of pharmacokinetic parameters allowed tailoring of dosing. First-order kinetics were observed. The calculated half-life of 3.52 h was less than reported by others, and the apparent volume of distribution (60 ml) was less than anticipated. The elimination constant was 0.197 h−1, Empiric dosing based on schedules suggested in the literature would have led to high peak and low mean concentrations of intrareservoir vancomycin. Patients with reservoir-associated infections have a variety of pathophysiologic conditions that can result in alteration of normal CSF dynamics. Pharmacokinetic analysis is useful to individualize dosing and to optimize therapy with intrareservoir vancomycin. [ABSTRACT FROM PUBLISHER]