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

We report here the results of a prospective trial of cessation of highly active antiretroviral therapy in individuals chosen for their success at achieving long-term virologic control

R. T. Davey; N. Bhat; C. Yoder; T.-W. Chun; J. A. Metcalf; R. Dewar; V. Natarajan; R. A. Lempicki; J. W. Adelsberger; K. D. Miller; J. A. Kovacs; M. A. Polis; R. E. Walker; J. Falloon; H. Masur; D. Gee; M. Baseler; D. S. Dimitrov; A. S. Fauci; H. C. Lane

2002

Scholarcy highlights

  • HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy in patients with a history of sustained viral suppression
  • Ex vivo labeling with bromo-2Ј deoxyuridine showed that CD4 and CD8 cell turnover increased after withdrawal of HAART and correlated with viral load whereas lymphocyte turnover decreased after reinitiation of drug treatment
  • Despite a mean period on effective suppressive therapy exceeding 2 years, varying degrees of virologic relapse occurred promptly in all individuals. These findings are especially notable for the consistency of HIV-1 rebound within only a few weeks of stopping drugs, and for the apparent lack of a significant treatment effect on the kinetics of viral relapse and, by implication, viral reservoirs. This cohort included a number of individuals in whom sensitive methods of viral quantitation identified little or no virus at baseline in the peripheral blood, lymph node tissue, cerebrospinal fluid, or pool of resting CD4ϩ T cells
  • Some of the IL-2-treated patients, in particular, had very low, sometimes unmeasurable, burdens of infectious virus in their resting CD4ϩ T cell pools, a trait already distinguishing them from most recipients of HAART alone
  • The lack of correlation between the number of latently infected cells and the HIV-1 dynamics after stopping HAART suggests the existence of a small reservoir of actively replicating virus that could be of major importance in rekindling viral replication
  • These findings underscore the results of earlier studies demonstrating persistence of HIV-1 RNA signal by PCR in peripheral blood mononuclear cells and lymph node tissue from treated patients, as well as more recent reports confirming that replication-competent HIV-1 can persist for long periods at low levels in the majority of treated individuals despite the use of maximally suppressive antiretroviral regimens
  • Laboratory surrogates indicating low or absent levels of measurable virus may provide useful comparative data on the relative potency of various therapeutic interventions, but do not as yet appear predictive of the ultimate success in maintaining control of viral replication once therapy is withdrawn

Need more features? Save interactive summary cards to your Scholarcy Library.