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15 June 1997 | Volume 126 Issue 12 | Pages 939-945
Background: Markers are needed for assessing response to antiretroviral therapy over time. The CD4+ lymphocyte count is one such surrogate, but it is relatively weak.
Objective: To assess the association of changes in plasma human immunodeficiency virus (HIV) RNA level and CD4+ lymphocyte count with progression to the acquired immunodeficiency syndrome (AIDS).
Design: Analysis of data from a subset of patients in a multicenter, randomized, clinical trial.
Setting: Six Veterans Affairs medical centers and one U.S. Army medical center.
Patients: 270 symptomatic HIV-infected patients from the Veterans Affairs Cooperative Study on AIDS.
Intervention: Patients were randomly assigned to receive zidovudine or placebo initially; a cross-over protocol was established for patients receiving placebo who had disease progression.
Measurements: Reverse transcriptase polymerase chain reaction on cryopreserved plasma samples, previously obtained CD4+ lymphocyte counts, and clinical events.
Results: For each decrease of 0.5 log10 copies/mL in plasma HIV RNA level, averaged over the 6 months after randomization, the relative risk (RR) for progression to AIDS was 0.67 (P < 0.001). In a subset of 70 treated patients with long-term follow-up, a return to baseline plasma HIV RNA levels within 6 months of randomization was associated with progression to AIDS (RR, 4.28; P = 0.004). Plasma HIV RNA levels or CD4+ lymphocyte counts over time were more strongly associated with progression to AIDS than were baseline levels or counts.
Conclusions: An adequate virologic response after initiation of antiretroviral therapy seems to require a decrease in plasma HIV RNA level of at least 0.5 log10 copies/mL that is sustained for at least 6 months. The independent relation between plasma HIV RNA level and CD4+ lymphocyte count over time and clinical outcome suggests that the measurement of plasma HIV RNA level, in addition to the CD4+ lymphocyte count, has a role in guiding the management of antiretroviral therapy.
Author and Article Information
For the VA Cooperative Study Group on AIDS*
ARTICLE
Changes in Plasma HIV RNA Levels and CD4+ Lymphocyte Counts Predict Both Response to Antiretroviral Therapy and Therapeutic Failure
For author affiliations and current author addresses, see end of text.
*For a listing of additional members of the VA Cooperative Study Group on AIDS, see Appendix.
Acknowledgment: The authors thank David Wolfberg for manuscript preparation.
Grant Support: In part by the Medical Research Service of the Department of Veterans Affairs, the Department of Defense, and Glaxo-Wellcome, Inc.
Requests for Reprints: William A. O'Brien, MS, MD, Infectious Disease Division, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0835.
Current Author Addresses: Dr. O'Brien: Infectious Disease Division, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0835.
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