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334 Rapid Clearance of HIV in Primary HIV-1 Infection: Relationship to Symptoms and Progression to AIDS
W. Blattner*1, K. Oursler1, F. Cleghorn1, M. Charurat1, A. Sill1, C. Bartholomew2, N. Jack2, J. Edwards2, D. Goodman3, M. Maurice3, K. Weinhold3, and M. Greenberg3
1Inst. of Human Virology, Baltimore, MD, USA; 2MRFTT, Trinidad; and 3Duke Univ., Durham, NC, USA
Background:The Trinidad Seroconvertor Cohort ascertained 30 individuals with acute HIV-1 infection between 1993 and 2001 by employing p24 antigen screening regardless of symptoms and followed 20 with analyzable data for this report.
Objective: To evaluate different measures of viral dynamics in relationship to clinical outcomes.
Methods: We employed a 2-stage analytical approach. In the first stage, a linear segmented regression model was fitted to estimate measures of viral load trajectory (change in log10 copies per month): the initial decline phase, the steady-state phase before loss of virologic control, and the failure phase. In the second stage, the effects of these virologic measures were evaluated in relationship to time to AIDS and clinical symptoms by Kaplan-Meier estimates and Cox regression.
Results: Of the 20 patients, 10 developed AIDS-defining events. The rate of initial viral clearance by those who did not develop AIDS was 2-fold greater than those who did (p = 0.04). Comparing individuals who developed AIDS with those that did not, the magnitude of the viral load steady state was no different, but the rate of subsequent virologic failure was 10-fold higher (p < 0.001). Compared with asymptomatic infection, symptomatic infection was associated with a more rapid clearance of initial viremia (median decline of 1.1 log10 per month vs. 0.5 log10 per month; p < 0.01) and viral load level at nadir (median 3.68 log10 copies vs. median 4.04 log10 copies; p = 0.07) but not with subsequent risk of AIDS.
Conclusions:These data demonstrate that the kinetics of viral clearance early in infection are linked to improved clinical outcome. The finding that early symptoms are associated with improved initial clearance of virus but not with subsequent outcome suggest that the cytokine response associated with symptoms and this initial clearance may involve different mechanisms than that associated with long-term virologic control. In depth studies of the immunologic responses surrounding these dynamic phases of initial viral clearance are important to understanding the correlates of immunity needed for an effective HIV vaccine.
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