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Raltregravir Question !

Discussion in 'XMRV Testing, Treatment and Transmission' started by ladybugmandy, Apr 19, 2010.

  1. ladybugmandy

    ladybugmandy *****

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    Hi all. I have been reading the research articles but am still unsure about something: is a higher concentration of Raltegravir required for XMRV, than it is for HIV? Or is it lower?

    One person told me you would need more Raltegravir for XMRV but I dont see that in the articles...

    Thank you
    Sue
  2. Gerwyn

    Gerwyn Guest

    according to the reduction in titres achieved in the following study I would say the same dose or probably less .i cant see the need for more and increasing the dose has an increased risk of more severe side effects.All drugs are controlled poisons!

    Raltegravir with Optimized Background Therapy for Resistant HIV-1 Infection
    Roy T. Steigbigel, M.D., David A. Cooper, M.D., D.Sc., Princy N. Kumar, M.D., Joseph E. Eron, M.D., Mauro Schechter, M.D., Ph.D., Martin Markowitz, M.D., Mona R. Loutfy, M.D., M.P.H., Jeffrey L. Lennox, M.D., Jose M. Gatell, M.D., Ph.D., Jurgen K. Rockstroh, M.D., Christine Katlama, M.D., Patrick Yeni, M.D., Adriano Lazzarin, M.D., Bonaventura Clotet, M.D., Jing Zhao, Ph.D., Joshua Chen, Ph.D., Desmond M. Ryan, B.S., Rand R. Rhodes, M.S., John A. Killar, M.S., Lucinda R. Gilde, B.S., Kim M. Strohmaier, B.S., Anne R. Meibohm, Ph.D., Michael D. Miller, Ph.D., Daria J. Hazuda, Ph.D., Michael L. Nessly, M.S., Mark J. DiNubile, M.D., Robin D. Isaacs, M.D., Bach-Yen Nguyen, M.D., Hedy Teppler, M.D., for the BENCHMRK Study Teams

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    ABSTRACT

    Background Raltegravir (MK-0518) is an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase active against HIV-1 susceptible or resistant to older antiretroviral drugs.

    Methods We conducted two identical trials in different geographic regions to evaluate the safety and efficacy of raltegravir, as compared with placebo, in combination with optimized background therapy, in patients infected with HIV-1 that has triple-class drug resistance in whom antiretroviral therapy had failed. Patients were randomly assigned to raltegravir or placebo in a 2:1 ratio.

    Results In the combined studies, 699 of 703 randomized patients (462 and 237 in the raltegravir and placebo groups, respectively) received the study drug. Seventeen of the 699 patients (2.4%) discontinued the study before week 16. Discontinuation was related to the study treatment in 13 of these 17 patients: 7 of the 462 raltegravir recipients (1.5%) and 6 of the 237 placebo recipients (2.5%). The results of the two studies were consistent. At week 16, counting noncompletion as treatment failure, 355 of 458 raltegravir recipients (77.5%) had HIV-1 RNA levels below 400 copies per milliliter, as compared with 99 of 236 placebo recipients (41.9%, P<0.001). Suppression of HIV-1 RNA to a level below 50 copies per milliliter was achieved at week 16 in 61.8% of the raltegravir recipients, as compared with 34.7% of placebo recipients, and at week 48 in 62.1% as compared with 32.9% (P<0.001 for both comparisons). Without adjustment for the length of follow-up, cancers were detected in 3.5% of raltegravir recipients and in 1.7% of placebo recipients. The overall frequencies of drug-related adverse events were similar in the raltegravir and placebo groups.

    Conclusions In HIV-infected patients with limited treatment options, raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks. (ClinicalTrials.gov numbers, NCT00293267 [ClinicalTrials.gov] and NCT00293254 [ClinicalTrials.gov] .)


    Source Information

    From the State University of New York at Stony Brook, Stony Brook (R.T.S.); National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney (D.A.C.); Georgetown University Medical Center, Washington, DC (P.N.K.); University of North Carolina, Chapel Hill (J.E.E.); Universidade Federal do Rio de Janeiro, Rio de Janeiro (M.S.); Aaron Diamond Research Center, Rockefeller University, New York (M.M.); University of Toronto, Toronto (M.R.L.); Emory University School of Medicine, Atlanta (J.L.L.); University of Barcelona, Barcelona (J.M.G.); University of Bonn, Bonn, Germany (J.K.R.); Hospital Piti–Salptrire, Universit Pierre et Marie Curie, Paris (C.K.); Hospital Bichat–Claude Bernard, Paris (P.Y.); San Raffaele Scientific Institute, Milan (A.L.); Hospital Germans Trias i Pujol, Fundacin Irsicaixa, Barcelona (B.C.); and Merck Research Laboratories, North Wales, PA (J.Z., J.C., D.M.R., R.R.R., J.A.K., L.R.G., K.M.S., A.R.M., M.D.M., D.J.H., M.L.N., M.J.D., R.D.I., B.-Y.N., H.T.).
  3. Hope123

    Hope123 Senior Member

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    That person is right based at least on the Singh article. I don't have my notes but this is the gist of what I recall. EC50 and EC90 refer to the concentrations of a drug need to inhibit 50% and 90% of activity, in this case reverse transcriptase activity as a proxy for viral replication. Comparing the EC50 and EC90 of AZT (listed by its other name, ZDV), you can see
    the EC50 and EC90 is HIGHER for XMRV than HIV (0.11 vs 0.0052; 7.3 vs. 0.036). This implies that a higher dose of AZT is needed to suppress XMRV vs. HIV and also holds for tenofiver and ratelgravir. This is in contrast to the Pathanik articles which says less ratelgravir is needed to suppress XMRV vs. HIV. Differences may be due to a number of reasons including how they measure inhibition.

    If I am reading figure 3 correctly, the best combo with the highest synergism value is ratelgravir and tenofiver. The next best would be either ratelgravir + AZT or ratelgravir+TDF (check out the ratios though) One good point to keep in mind is that the Singh article was written without the involvment of pharma support so as far as I know, they don't seem to be pushing a particular drug for sales purposes.

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