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Changes in Plasma HIV RNA Levels and CD4+ Lymphocyte Counts Predict Both Response to Antiretroviral Therapy and Therapeutic Failure

William A. O'Brien, MS, MD; Pamela M. Hartigan, MPH, PhD; Eric S. Daar, MD; Michael S. Simberkoff, MD; and John D. Hamilton, MD
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For the VA Cooperative Study Group on AIDS* 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.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;126(12):939-945. doi:10.7326/0003-4819-126-12-199706150-00002
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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.


Grahic Jump Location
Figure 1.
Kaplan-Meier analysis of the time to progression to the acquired immunodeficiency syndrome (AIDS) in 70 patients whose human immunodeficiency virus (HIV) RNA plasma levels did or did not return to baseline (left) or whose CD4+ lymphocyte counts did or did not return to baseline (right) in less than 6 months.P

The value for the difference between the groups is shown for each marker.

Grahic Jump Location




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