Context.-Pediatric human immunodeficiency virus (HIV) infection has unique viral pathogenetic features that preclude routine extrapolation from adult studies and require specific analysis.Objectives.-To evaluate the prognostic value of 2 key laboratory markersplasma RNA and CD4 + lymphocyte count-for HIV disease progression in infants and children and to establish targeted values for optimal outcome.Design.-Data from a cohort of 566 infants and children who participated in a randomized, placebo-controlled trial of nucleoside reverse transcriptase inhibitors (ACTG 152) were analyzed. The trial was conducted between 1991 and 1995 and enrolled a heterogenous cohort of antiretroviral therapy-naive children (age, 3 months to 18 years); patients had a median follow-up of 32 months.Main Outcome Measures.-The trial clinical end points consisted of time to first HIV disease progression (growth failure, decline in neurologic or neurodevelopmental function, opportunistic infections) or death.Results.-Baseline plasma RNA levels were high (age group medians, 5ϫ10 4 to Ͼ10 6 copies/mL), and both baseline RNA and CD4 + lymphocyte count were independently predictive of subsequent clinical course. Risk reduction for disease progression between 49% and 64% was observed for each log 10 reduction in baseline RNA and was linear without suggestion of a threshold or age effect. Disease progression predictive power was enhanced by the combined use of plasma RNA and CD4 + cell count. Marker values of less than 10 000 copies/mL for plasma RNA and greater than 500ϫ10 6 /L (Ͻ6.5 years of age) or greater than 200ϫ10 6 /L (Ͼ6.5 years) for CD4 + cell count were associated with a 2-year disease progression rate of less than 5%.Conclusions.-Two key laboratory markers-plasma RNA and CD4 + lymphocyte count-are independent predictors of clinical course among HIV-infected infants and children. The linear, age-independent relationship between log 10 plasma RNA and relative risk of disease progression strongly supports therapeutic efforts to achieve plasma virus levels as low as possible.
T-1249 is a 39-aa synthetic peptide that inhibits fusion of human immunodeficiency virus (HIV) to the host target cell. A 14-day open-label, phase 1/2 dose-escalation monotherapy study of the safety and antiretroviral activity of T-1249 was performed on 115 HIV-1-infected adults. At baseline, the majority of the patients had advanced HIV disease (baseline median CD4(+) cell count, 57 cells/microL) and had extensive pretreatment (i.e., pre-T-1249) experience with antiretroviral medications (median, 11 antiretroviral drugs). Patients received T-1249 monotherapy by subcutaneous injection, for 14 days, at doses ranging from 6.25 to 192 mg/day. T-1249 was generally well tolerated, and no dose-limiting toxicity was identified. Injection-site reactions were the most commonly reported adverse event (57%). Dose-dependent decreases in plasma HIV-1 RNA load were observed; the median maximum change from baseline across dose groups ranged from -0.29 log(10) copies/mL (95% confidence interval [CI], -0.43 to -0.05 log(10) copies/mL) for the lowest dose to -1.96 log(10) copies/mL (95% CI, -2.02 to -1.37 copies/mL) for the highest dose. These results indicate that T-1249 is a potent new therapeutic agent for HIV-1 infection.
Aim: To identify the possible factors determining the dose of warfarin prescribed in patients receiving anticoagulant treatment. Methods: The computerised records of 2305 patients maintained on the drug in seven hospitals were amalgamated and classified into one of seven diagnostic groups. The associations with the dose of warfarin prescribed were investigated by univariate and multiple regression analysis. Differences between hospitals were studied with regard to the coagulometric method and the thromboplastin preparation used. Results: The geometric mean dose of warfarin was 4 57 mg and 5% of patients were prescribed 10 mg or greater. There was a noticeable decrease in dose with increasing age, which averaged about 6 mg for patients aged 30 but 3*5 mg for doses of warfarin among hospitals indicates that further efforts to improve uniformity are required.AC is a software system for personal computers which assists in the outpatient maintenance of warfarin treatment. It is a development of the system originally described byWilson and James' and keeps records whose primary purpose is to furnish details necessary for the continued management of patients. A by-product, however, is its potential for the study of statistics relating to treatment. As the records produced by the system have a uniform structure, data from several centres can be amalgamated. Of the hospitals using AC, seven kindly allowed us to study their data files, providing records on 2305 patients receiving warfarin.
In symptomatic HIV-infected children, treatment with either didanosine alone or zidovudine plus didanosine was more effective than treatment with zidovudine alone. The efficacy of didanosine alone was similar to that of the combination therapy and was associated with less hematologic toxicity.
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