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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

  1. Author:
    McMahon, D.
    Jones, J.
    Wiegand, A.
    Gange, S. J.
    Kearney, M.
    Palmer, S.
    McNulty, S.
    Metcalf, J. A.
    Acosta, E.
    Rehm, C.
    Coffin, J. M.
    Mellors, J. W.
    Maldarelli, F.

  2. Author Address

    [McMahon, D.; Jones, J.; McNulty, S.; Mellors, J. W.] Univ Pittsburgh, Dept Infect Dis, Pittsburgh, PA USA. [Wiegand, A.; Kearney, M.; Palmer, S.; Coffin, J. M.; Maldarelli, F.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [Gange, S. J.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Metcalf, J. A.; Rehm, C.] NIAID, Clin Res Sect, NIH, Bethesda, MD 20892 USA. [Acosta, E.] Univ Alabama, Dept Pharmacol, Birmingham, AL USA.;Maldarelli, F, NCI, NIH, Bldg 10,Rm 5A06, Bethesda, MD 20892 USA.;fmalli@mail.nih.gov
    1. Year: 2010
    2. Date: Mar
  2. Journal: Clinical Infectious Diseases
    1. 50
    2. 6
    3. Pages: 912-919
  4. Type of Article: Article
  5. ISSN: 1058-4838
  1. 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 (similar to 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 log(10) copies/mL), during (0.04 log(10) copies/mL), and after (0.04 log(10) 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.

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External Sources

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  2. DOI: 10.1086/650749
  3. View record in Web of Science®
  4. WOS: 000274656000019

Library Notes

  1. Fiscal Year: FY2009-2010
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