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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Evaluation of guidelines for initiation of highly active antiretroviral therapy in a longitudinal cohort of HIV-infected individuals.

OBJECTIVES: Expert panels have developed several guidelines for initiating highly active antiretroviral therapy (HAART) in patients with HIV infection. To evaluate these guidelines, we simulated their application in a cohort of HIV-infected patients established and followed before HAART was available, and determined how long such patients survived without disease progression in the absence of HAART. METHODS: Longitudinal data was used that had been collected from 1982 to 1995 on a prospective cohort of 133 homosexual men with known or closely approximated dates of HIV-1 seroconversion and negligible antiretroviral exposure. The main definition of disease progression was CD4 cell count < or = 300x10(6)/l or development of clinical AIDS diagnosis within 12 months. RESULTS: The mean number of years between the recommended initiation of therapy and when disease progression occurred in the absence of HAART were as follows: initiation of treatment at first visit, 4.81 years [median, 3.78 years; interquartile range (IQR), 1.85-6.59 years]; CD4 cell count <500x10(6)/l or serum RNA >5000 copies/ml (at least 10000 copies/ml fresh plasma), 4.35 years (median, 3.22 years; IQR, 1.56-6.19 years); CD4 cells <500x10(6)/l or serum RNA >20000 copies/ml (at least 40000 copies/ml fresh plasma), 3.61 years (median, 2.70 years; IQR, 1.40-5.11 years); and CD4 cells <500x10(6)/l, 2.72 years (median, 2.17 years; IQR, 0.81-4.25 years). The percentage of patients who had disease progression before HAART would have been recommended was 0.8, 1.6, 3.2 and 13.6% with each of these four approaches, respectively. CONCLUSIONS: Implementation of recommended treatment guidelines will result in a substantial proportion of patients being treated for long periods before immunologic or clinical disease progression would have occurred in the absence of HAART. These findings should be considered in the clinical care of HIV-infected patients and in future recommendations for the initiation of HAART.[1]

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