Studies

A randomized, open-label, comparative trial of AZT/3TC versus AZT/3TC/ddI in antiretroviral naïve HIV-1 infected Thai patients

December 31, 1998

Project no.: HIV-NAT 003

Background:

  • An in vitro study comparing the ability of ten different three-drug combinations to prevent HIV-induced cytopathic effects in continuous T-lymphoblastoid cell line showed superior activity of AZT/3TC/ddI
  • Thai study will compare the triple combination of AZT/3TC/ddI versus a control arm of AZT/3TC
  • Triple nucleosides regimens may be an appropriate alternative to costlier protease inhibitor-containing regimens

Objectives: To evalute tolerance and comparative virologic and immunologic efficacy of AZT in combination with 3TC versus AZT in combination with 3TC and ddI

Trial design:

  • Randomized, open-label, comparative, two-center study
  • Primary endpoint will be suppression of plasma HIV-RNA and absolute change in CD4 cells/mm3 from baseline
  • The duration of the study is 48 weeks

Treatment: AZT 300 (200*) mg + 3TC 150 mg BID

Arms: AZT 300 (200*) mg + 3TC 150 mg + ddI 200 (125*) mg BID (*if subject weight < 60 kg)

Entry criteria:

  • Antiretroviral naïve
  • CD4+ cell count of 100-500 /mm3
  • No active or ongoing opportunistic infection/disease

Methods:

  • 106 HIV-1 infected Thai with CD4 counts between 100 and 500 cells/mm3, free from any active or ongoing opportunistic infection were equally randomized to receive either AZT/3TC or AZT/3TC/ddI for 48 weeks
  • Patients were accessed at screening, randomization, and at weeks 2, 4, 12, 24, 36, and 48 to determine:
    • the degree and duration of plasma HIV-RNA reduction as measured by bDNA assay (limit of detection 500 copies/ml)
    • changes in CD4+ lymphocyte count
    • Safety and tolerance of the treatment regimens

Result:

  • Both regimens were well tolerated
  • Adverse events related to study drug were mild and equally destributed between the two arms
  • The three most frequent adverse events were nausea, vomiting and anorexia
  • Laboratory abnormalities include 1 patient with Grade IV neutropenia and Grade III anemia at week 12-19 and 1 patient with Grade III anemia and Grade IV neutropenia at week 12-14 which resolved upon temporally treatment discontinuation. 1 patient had grade IV ALT at the day of beginning study treatment.
  • Reduction in viral load was significantly greater in the AZT/3TC/ddI arm compared to AZT/3TC arm (p = 0.0031) when ultrasensitive assay (LD 50 copies/ml) was used