Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy

Academic Article

Abstract

  • Background. Combination antiretroviral therapy suppresses but does not eradicate human immunodeficiency virus type 1 (HIV-1) in infected persons, and low-level viremia can be detected despite years of suppressive antiretroviral therapy. Short-course (28-day) intensification of standard antiretroviral combination therapy is a useful approach to determine whether complete rounds of HIV-1 replication in rapidly cycling cells contribute to persistent viremia. We investigated whether intensification with the integrase inhibitor raltegravir decreases plasma HIV-1 RNA levels in patients receiving suppressive antiretroviral therapy. Methods. Subjects (n = 10) with long-term HIV-1 suppression receiving combination antiretroviral regimens had their regimens intensified for 4 weeks with raltegravir. Plasma HIV-1 RNA level was determined before, during, and after the 4-week intensification period, using a sensitive assay (limit of detection, 0.2 copies of HIV-1 RNA/ mL of plasma). A 4-week intensification course was chosen to investigate potential HIV-1 replication in cells with relatively short (∼l-14-day) half-lives. Results. There was no evidence in any subject of a decline in HIV-1 RNA level during the period of raltegravir intensification or of rebound after discontinuation. Median levels of HIV-1 RNA before (0.17 log10 copies/mL), during (0.04 log l0 copies/mL), and after (0.04 logl0) copies/mL) raltegravir intensification were not significantly different (P> .1 for all comparisons in parametric analyses). High-performance liquid chromatography and mass spectroscopy experiments confirmed that therapeutic levels of raltegravir were achieved in plasma during intensification. Conclusions. Intensification of antiretroviral therapy with a potent HIV-1 integrase inhibitor did not decrease persistent viremia in subjects receiving suppressive regimens, indicating that rapidly cycling cells infected with HIV-1 were not present. Eradication of HIV-1 from infected persons will require new therapeutic approaches. Trial registration. ClinicalTrials.gov identifier: NCT00618371. © 2010 by the Infectious Diseeses Society of America. All rights reserved.
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    Author List

  • McMahon D; Jones J; Wiegand A; Gange SJ; Kearney M; Palmer S; McNulty S; Metcalf JA; Acosta E; Rehm C
  • Start Page

  • 912
  • End Page

  • 919
  • Volume

  • 50
  • Issue

  • 6