HIV-1 pol replication capacity predicts disease progression

Objective: To determine the influence of pol replication capacity on the natural history of HIV-1 infection. Design: Pol replication capacity was measured using a recombinant virus single cycle assay on baseline plasma specimens from subjects enrolled in the Hemophilia Growth and Development Study. Setting: Children and adolescents with hemophilia and HIV-1 infection were enrolled at multiple sites across the USA into a natural history study. Participants: The Hemophilia Growth and Development Study enrolled 207 HIV-1-infected hemophiliacs between 6 and 19 years of age in 1989 and 1990. Subjects were followed every 6 months through 1997 with pol replication capacity measurements available from 128 of the subjects. Main outcome measures: A univariate model defined the relationship between pol replication capacity and HIV-1 RNA and CD4 T-cell number. A random effects model assessed the ability of this measure to predict CD4 T-cell decline over time and a Cox proportional hazards model and Kaplan-Meier analyses defined how it predicts clinical progression. Results: Pol replication capacity measures correlated with baseline HIV-1 RNA, R 2 = 0.189 (P = 0.03) and CD4 T-cell number, -0.197 (P = 0.03). It also independently predicted CD4 T-cell decline over time and progression to AIDS. Conclusions: This study demonstrates that pol replication capacity independently influences the natural history of HIV-1 infection.