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To evaluate the relationship between the HIV viral burden in individuals prior to receiving highly-active antiretroviral therapy (HAART) and the viral burden after withdrawal of HAART.Retrospective cohort study at the National Institutes of Health, Bethesda, Maryland, USA.Fourteen HIV-infected patients who achieved and maintained viral control on HAART who subsequently discontinued HAART.Pre- and post-HAART viral loads measured from plasma or serum.Patients achieved viral control (< 500 copies/ml) on HAART in a median 28 days (range, 15–490 days; mean, 72 days), maintained viral control for a median 661 days (range, 53–1067 days; mean, 611 days), and subsequently discontinued HAART for a median 49 days (range, 14–196 days; mean, 73 days). The median difference between the pre- and post-HAART viral loads was 0.16 log10 (range, −0.72 to 1.05 log10; mean, 0.19 log10). The median absolute difference between the pre- and post-HAART viral loads was 0.43 log10 (range, 0.06–1.05 log10; mean, 0.46 log10). Nine individuals had post-HAART values higher than pre-HAART values, five had lower values. Median duration between pre- and post-HAART viral load measurements was 1757 days (range, 117–3177 days; mean, 1756 days), or 4.8 years.After discontinuing HAART, individuals had rebounds in their viral burdens approximating pre-HAART levels, even after a significant lapse of time approaching 5 years. Our data suggest that an intrinsic viral load set-point may exist, and that a single interruption of an effective regimen with viral suppression for almost 2 years does not significantly alter this set-point.