Alternative multidrug regimen provides improved suppression of HIV-1 replication over triple therapy

Authors:
  • JLJoep M.A. Lange
    Joep M.A. Lange
  • SJSuzanne Jurriaans
    Suzanne Jurriaans
  • JPJan M. Prins
    Jan M. Prins
  • VLVladimir V. Lukashov
    Vladimir V. Lukashov
  • DNDaan W. Notermans
    Daan W. Notermans
  • MRMarijke Roos
    Marijke Roos
  • HSHanneke Schuitemaker
    Hanneke Schuitemaker
  • RHRichard M.W. Hoetelmans
    Richard M.W. Hoetelmans
  • SDSven A. Danner
    Sven A. Danner
  • JGJaap Goudsmit
    Jaap Goudsmit
  • FWFrank de Wolf
    Frank de Wolf
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Abstract
To compare the viral suppression of two antiretroviral regimens using three drugs or five drugs. Two open-label studies using a three-drug (zidovudine, lamivudine and ritonavir) and a five-drug regimen (zidovudine, lamivudine, abacavir, indinavir and nevirapine) in study-drug-naive patients, except for one in the five-drug study. Participants with ≥ 10 000 HIV-1 RNA copies/ml in plasma at baseline were compared by means of Kaplan-Meier curves for time to < 50 copies/ml, as well as linear regression analysis for the first phase of decline using log-transformed copy numbers. The elimination rate constants for HIV-1 RNA in 15 participants of the three-drug study were compared with nine participants of the five-drug study. The level of < 50 copies/ml was reached earlier when using the five-drug than when using the three-drug regimen (P log rank = 0.0005): median time to reach this level was 4 weeks and 12 weeks, respectively. No differences were found in HIV-1 RNA elimination rate constants in the first 2 weeks after the initiation of therapy. When the viral load declines were calculated from day 2 onwards, adjusting for differences in pharmacological delay of the drugs used, again no differences in early viral load decline were found between the two regimens. With the five drugs used in this study, the median time to reach < 50 HIV-1 RNA copies/ml was 8 weeks shorter than with the three-drug regimen. This finding shows that suppression of viral load in HIV-infection by standard triple-drug therapy can be improved upon.

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