To investigate the toxicity, antiviral activity, and pharmacokinetics in HIV-infected
patients receiving 16 weeks of oral saquinavir mesylate ( Ro 31-8959 ) at one of two doses.
Cohorts of 16 patients receive 1 of 2 doses of Ro 31-8959 for 20 weeks. Administration of
the higher dose will proceed only after 2-week safety data for the first eight patients on
the lower dose has been reviewed.
Patients must have:
- Documented HIV infection.
- CD4 count 200 - 500 cells/mm3.
- No evidence of viral resistance.
- HIV RNA quantifiable by PCR.
- Negativity for HBsAg, HBeAg, and anti-HBc.
- Fifty percent of patients must have measurable p24 antigen levels (> 31 pg/ml).
Patients with the following symptoms or conditions are excluded:
- Active opportunistic infection requiring immediate treatment, such as tuberculosis,
cytomegalovirus, cerebral toxoplasmosis, and Pneumocystis carinii pneumonia.
- Unable to maintain adequate oral intake.
- Clinically significant vomiting and/or diarrhea.
- Malignancy, visceral Kaposi's sarcoma, or lymphoma that will require systemic
chemotherapy within the next 12 months.
- Unable to comply with protocol requirements, in the judgment of the investigator.
- Any grade 3 or worse laboratory or clinical abnormality.
- Antineoplastic agents.
- Concomitant or maintenance treatment with excluded experimental drugs and drugs with
known nephrotoxic or hepatotoxic potential.
- Radiation therapy other than local skin radiation therapy.
Patients with the following prior conditions are excluded:
- Unexplained temperature >= 38.5 C (101.5 F) persisting for 14 days or more within a
- Unexplained, chronic diarrhea persisting for 14 days or more within a 30-day period.
- Prior treatment with an HIV proteinase inhibitor.
- AZT within 30 days prior to study entry OR lasting more than 1 year.
- Other antiretroviral therapy (besides AZT) within 30 days prior to study entry OR
lasting more than 14 days.
- Acute therapy for an opportunistic infection within 14 days prior to study entry.