Studies

A phase 2 randomized, four arm, open-label, comparative trial to evaluate the efficacy and tolerance of combination antiretroviral therapy with ddI + d4T alone or in combination with either nevirapine, hydroxyurea or both nevirapine and hydroxyurea for the treatment of HIV-1 infection in a Thai study population

December 31, 1998

Project no.: HIV-NAT 006

Introduction:

  • Hydroxyurea (HU) blocks DNA synthesis by inhibitoion of the cellular enzyme ribonucleotide reductase. It has been shown in vitro to block HIV-1 infection in acutely infected human lymphocytes and macrophages. In vitro synergy with ddI has also been demonstrated
  • Nevirapine, the first drug developed in the non-nucleoside class, has been shown to have beneficial effects on CD cell counts and HIV-1 viral load when given with combination nucleoside antiretroviral regimens

Study Regimens:

  • ddI + d4T
  • ddI + d4T + hydroxyurea
  • ddI + d4T + nevirapine
  • ddI + d4T + nevirapine + hydroxyurea

Study Objectives:

  • Primary:
    • To compare the time weighted change in plasma HIV-1 RNA load from baseline in each arm as a measure of relative efficacy
    • To access safety and tolerance of the four different regimens based in clinical and laboratory adverse events
  • Secondary:
    • To evaluate the time weighted changed in absolute CD4+ cell counts and CD4/CD8 ratio from baseline in each regimens
    • To access efficacy of the different regimens on survival and HIV disease progression

Study Design:

  • Total of 200 antiretroviral naïve participants will be recruited over a 6 month period and equally randomized to one of the four study arms
  • Participants should have CD4+ cell count of at least 150 cells/nn3 and HIV-RNA viral load of at least 10,000 copies/ml
  • Duration of study is 48 weeks