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Journal of Virology, November 2003, p. 12165-12172, Vol. 77, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.22.12165-12172.2003

Viral Blip Dynamics during Highly Active Antiretroviral Therapy

Michele Di Mascio,1,{dagger} Martin Markowitz,2 Michael Louie,2 Christine Hogan,2 Arlene Hurley,2 Chris Chung,2 David D. Ho,2 and Alan S. Perelson1*

Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545,1 Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 100162

Received 17 June 2003/ Accepted 9 August 2003

Although intermittent episodes of low-level viremia are often observed in well-suppressed highly active antiretroviral therapy (HAART)-treated patients, the timing and amplitude of viral blips have never been examined in detail. We analyze here the dynamics of viral blips, i.e., plasma VL measurements of >50 copies/ml, in 123 HAART-treated patients monitored for a mean of 2.6 years (range, 5 months to 5.3 years). The mean (± the standard deviation) blip frequency was 0.09 ± 0.11/sample, with about one-third of patients showing no viral blips. The mean viral blip amplitude was 158 ± 132 human immunodeficiency virus type 1 (HIV-1) RNA copies/ml. Analysis of the blip frequency and amplitude distributions suggest that two blips less than 22 days apart have a significant chance of being part of the same episode of viremia. The data are consistent with a hypothetical model in which each episode of viremia consists of a phase of VL rise, followed by two-phase exponential decay. Thus, the term "viral blip" may be a misnomer, since viral replication appears to be occurring over an extended period. Neither the frequency nor the amplitude of viral blips increases with longer periods of observation, but the frequency is inversely correlated with the CD4+-T-cell count at the start of therapy, suggesting that host-specific factors but not treatment fatigue are determinants of blip frequency.

* Corresponding author. Mailing address: MS-K710, T-10, Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545. Phone: (505) 667-6829. Fax: (505) 665-3493. E-mail: asp{at}lanl.gov.

{dagger} Present address: National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.

Journal of Virology, November 2003, p. 12165-12172, Vol. 77, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.22.12165-12172.2003




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