HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression

Identifying the immunologic and virologic consequences of discontinuing ant iretroviral therapy in HIV-infected patients is of major importance in deve loping long-term treatment strategies for patients with HIV-1 infection, We designed a trial to characterize these parameters after interruption of hi ghly active antiretroviral therapy (HAART) in patients who had maintained p rolonged viral suppression on antiretroviral drugs. Eighteen patients with CD4(+) T cell counts greater than or equal to 350 cells/mu l and viral load below the limits of detection for greater than or equal to 1 year while on HAART were enrolled prospectively in a trial in which HAART was discontinu ed. Twelve of these patients had received prior IL-2 therapy and had low fr equencies of resting, latently infected CD4 cells. Viral load relapse to >5 0 copies/ml occurred in all 18 patients independent of prior IL-2 treatment , beginning most commonly during weeks 2-3 after cessation of HAART. The me an relapse rate constant was 0.45 (0.20 log(10) copies) day(-1), which was very similar to the mean viral clearance rate constant after drug resumptio n of 0.35 (0.15 log(10) copies) day(-1) (P = 0.28), One patient experienced a relapse delay to week 7. All patients except one experienced a relapse b urden to > 5,000 RNA copies/ml, Ex vivo labeling with BrdUrd showed that CD 4 and CD8 cell turnover increased after withdrawal of HAART and correlated with viral load whereas lymphocyte turnover decreased after reinitiation of drug treatment. Virologic relapse occurs rapidly in patients who discontin ue suppressive drug therapy, even in patients with a markedly diminished po ol of resting, latently infected CD4(+) T cells.