To compare the safety, tolerance, early antiviral activity, and durability of antiviral
response of the lamivudine (3TC)/zidovudine (ZDV)/1592U89 arm versus the 3TC/ZDV/indinavir
(IDV) arm. To determine the effect of the two arms on clinical efficacy as determined by the
occurrence of new CDC, defined class B/C events, survival, medical resource utilization, and
the development of plasma viral genotypic and phenotypic resistance.
In this international study, 550 patients are randomized (225 per arm) to receive Combivir
in combination with 1592U89 or indinavir. If after 16 weeks (and every 8 weeks thereafter
until week 48) a patient has HIV-1 RNA >= 400 copies/ml (by PCR on two occasions >= 1 week
and < 4 weeks apart), the patient has the option to switch to open-label therapy consisting
of indinavir, 1592U89, and Combivir.
GM-CSF, G-CSF, and erythropoietin.
Local treatment for Kaposi's sarcoma.
Patients must have:
- HIV-1 infection documented by a licensed HIV-1 antibody ELISA and confirmed by
Western blot detection of HIV-1 antibody or positive HIV-1 blood culture.
- CD4+ cell count >= 100 cells/mm3 within 14 days prior to study drug administration.
- HIV-1 RNA >= 10,000 copies/ml within 14 days prior to study drug administration.
- No active diagnosis of AIDS according to the 1993 Centers for Disease Control (CDC)
AIDS surveillance definition (excluding CD4+ cell counts < 200 cells/mm3).
- Signed, informed consent from parent or legal guardian for patients under 18 years of
Patients with the following conditions or symptoms are excluded:
- Malabsorption syndrome or other gastrointestinal dysfunction that may interfere with
- Serious medical conditions such as diabetes, congestive heart failure,
cardiomyopathy, or other cardiac dysfunction that would compromise the safety of the
- Cytotoxic chemotherapeutic agents.
- Agents with documented anti-HIV-1 activity in vitro.
- Immunomodulating agents such as systemic corticosteroids, interleukins, thalidomide,
- Terfenadine, astemizole, cisapride, triazolam, midazolam, and
- Radiation therapy.
- Other investigational treatments. NOTE:
- Treatments available through treatment IND or other expanded access programs are the
exception and evaluated individually.
Patients with the following prior conditions are excluded:
History of relevant pancreatitis or hepatitis in the last 6 months.
- Cytotoxic chemotherapeutic agents within 30 days of study drug administration.
- Prior antiretroviral therapy.
- HIV vaccine dose within 90 days of study drug administration.
- Immunomodulating agents such as systemic corticosteroids, interleukins, or
interferons within 30 days of study entry.
Radiation therapy within 30 days of study drug administration.
Current alcohol or illicit drug use that may interfere with patient compliance.