HIV-1 Messenger RNA in Peripheral Blood Mononuclear Cells as an Early Marker of Risk for Progression to AIDS

  1. Kalle Saksela, MD, PhD;
  2. Cladd E. Stevens, MD;
  3. Pablo Rubinstein, MD;
  4. Patricia E. Taylor, PhD; and
  5. David Baltimore, PhD
  1. From the Rockefeller University and the New York Blood Center, New York, New York; and the Massachusetts Institute of Technology, Cambridge, Massachusetts. Grant Support: In part by grant A122346 from the National Institutes of Health (Dr. Baltimore) and the Aaron Diamond Foundation for AIDS research (Dr. Saksela). Requests for Reprints: Kalle Saksela, MD, PhD, The Rockefeller University, Box 285, 1230 York Avenue, New York, NY 10021. Current Author Addresses: Dr. Saksela: The Rockefeller University, Box 285, 1230 York Avenue, New York, NY 10021.

    Abstract

    Objective: To establish human immunodeficiency virus type 1 (HIV-1) messenger RNA (mRNA) expression in peripheral blood mononuclear cells as a marker of risk for progression to the acquired immunodeficiency syndrome (AIDS) in a large cohort of HIV-infected persons followed for a prolonged period.

    Design: Retrospective testing of cryopreserved, coded specimens.

    Setting: Research laboratories at the New York Blood Center and the Rockefeller University.

    Patients: 150 homosexual men infected with HIV-1 who did not have an AIDS diagnosis at the time of testing.

    Measurements: Multiply spliced and unspliced HIV-1 mRNAs in total peripheral blood mononuclear cell RNA were quantitated using reverse transcriptase-initiated polymerase chain reaction (PCR) and compared with other laboratory data and clinical outcome during the subsequent 8 years.

    Results: Although HIV-1 mRNA expression generally correlated with immunologic status, it was associated with future disease progression independently of CD4+ cell counts or their rate of decrease at the time of sampling. The association of HIV-1 mRNA with disease progression in persons with CD4+ cell counts higher than the median (> 624 cells/mm3) was particularly noteworthy; further variation in the CD4+ cell counts within this group was not prognostically significant.

    Conclusions: The expression of HIV-1 mRNA in peripheral blood mononuclear cells is a strong independent marker for future HIV disease progression, even in persons with normal T-cell subsets.

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