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Biological and Virologic Characteristics of Primary HIV Infection

Timothy W. Schacker, MD; James P. Hughes, PhD; Theresa Shea, PAC; Robert W. Coombs, MD, PhD; and Lawrence Corey, MD
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From the University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, Washington. Acknowledgments: The authors thank Ann C. Collier, MD, for assistance with protocol design and manuscript review; Eric Peterson and the staff of the University of Washington Retrovirology Laboratory for their dedication and hard work; and the study participants for their dedication and commitment. Grant Support: In part by grants AI-26657, AI-01228, AI-45206, and AI-35605 from the National Institutes of Health. Requests for Reprints: Lawrence Corey, MD, Fred Hutchinson Cancer Research Center, 1124 Columbia Street (M-115), Seattle, WA 98104. Current Author Addresses: Dr. Schacker: Department of Medicine, Box 250, University of Minnesota, 516 Delaware Street SE, Minneapolis, MN 55455.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1998;128(8):613-620. doi:10.7326/0003-4819-128-8-199804150-00001
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Background: The clinical events surrounding acute HIV-1 infection have been well described, but little is known about whether the virologic course of acute HIV-1 infection influences the subsequent progression of disease.

Objective: To define the virologic natural history of acute and very early HIV infection.

Design: Prospective, longitudinal cohort study.

Setting: University of Washington Research Clinic

Participants: 74 adults enrolled soon after acquisition of HIV (mean, 69 days).

Measurements: Plasma HIV-1 RNA levels; quantitative cell cultures; CD4 cell counts; and detailed clinical assessments done at study entry, biweekly for 1 month, monthly for 2 months, and quarterly thereafter.

Results: In the first 30 days after acquisition of HIV, HIV-1 RNA levels varied greatly among participants (range, 27 200 to 1.6 × 106 copies per mL of plasma). Levels of HIV-1 RNA decreased by a mean of 6.5% per week for the first 120 days and then increased by a mean of 0.15% per week. CD4 cell counts decreased by a mean of 5.2 cells/mm3 per week for the first 160 days and by a mean of 1.9 cells/mm3 per week thereafter (P < 0.01). Disease progressed faster in participants who sought medical care for their acute seroconversion syndrome (P = 0.01) and those who had high plasma HIV-1 RNA levels 120 to 365 days after acquisition (P < 0.01). Peak levels in the first 120 days were not predictive of disease progression.

Conclusions: The variability in viral RNA levels associated with acute HIV-1 infection is greater than previously appreciated. Within 120 days of acquisition, plasma HIV RNA levels rapidly decrease to an inflection point, after which they gradually increase. Virus-host interactions soon after acquisition seem to have a major influence on the long-term outcome of HIV-1 disease.


Grahic Jump Location
Figure 1.
Scatterplot of plasma HIV-1 RNA levels (x103/mL) and median plasma HIV-1 RNA levels in the cohort from the time of seroconversion.
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Grahic Jump Location
Figure 3.
Kaplan-Meier analysis of time to a CD4 cell count of 300 cells/mm3 or less for persons who consulted a physician about symptoms of HIV seroconversion (dotted line) and those who did not (solid line).
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Grahic Jump Location
Figure 2.
Participants with initially low and subsequently high plasma HIV-1 RNA levels.topbottom

Plasma HIV RNA levels (×) and CD4 cell counts (o) are plotted from the time of study entry. Each point represents the median value for the 0- to 3-, 4- to 6-, 7- to 9-, 10- to 12-, and 13- to 15-month intervals after acquisition. Both participant 1 ( ) and participant 2 ( ) had relatively low plasma HIV RNA levels in the first 4 months after acquisition and subsequent increase in viral level and rapid rate of CD4 cell loss.

Grahic Jump Location




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