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

AbstractBACKGROUND:
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 (approximately 1-14-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 log10 copies/mL), and after (0.04 log10 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.
AuthorsD McMahon, J Jones, A Wiegand, S J Gange, M Kearney, S Palmer, S McNulty, J A Metcalf, E Acosta, C Rehm, J M Coffin, J W Mellors, F Maldarelli
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 50 Issue 6 Pg. 912-9 (Mar 15 2010) ISSN: 1537-6591 [Electronic] United States
PMID20156060 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-HIV Agents
  • Pyrrolidinones
  • RNA, Viral
  • Raltegravir Potassium
Topics
  • Adult
  • Aged
  • Anti-HIV Agents (administration & dosage)
  • Antiretroviral Therapy, Highly Active (methods)
  • Female
  • HIV Infections (drug therapy, virology)
  • HIV-1 (isolation & purification)
  • Humans
  • Male
  • Middle Aged
  • Pyrrolidinones (administration & dosage)
  • RNA, Viral (blood)
  • Raltegravir Potassium
  • Viral Load
  • Viremia

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