To determine the virologic benefits associated with the addition of hydroxyurea (HU) to
combination drug therapy with didanosine (ddI), stavudine (d4T), and efavirenz (DMP) in
HIV-infected patients. To assess the safety and tolerance of this regimen, with or without
HU or placebo is added 30-60 days after the initiation of DMP, ddI, and d4T combination
therapy. Patients are stratified according to antiretroviral experience (naive or
experienced). Patients are followed for 48 weeks to determine safety, efficacy, and effect
of treatment on viral, immunologic,and biochemical parameters.
Patients must have:
- HIV infection, as documented by a licensed ELISA that is confirmed either by Western
blot, positive HIV culture, positive HIV antigen, positive plasma HIV RNA, or a
second antibody test positive by a method other than ELISA.
- CD4 cell count of at least 100 cells/mm3 within 30 days of study entry.
- Over 500 HIV-1 RNA copies/ml as measured by the Roche Amplicor or Ultra Sensitive
Assay within 30 days of study entry.
- Treatment-experienced patients must have documented HIV RNA values of less than or
equal to 100,000 copies/ml within 30 days of study entry.
Acute therapy for an infection or other medical illness. Acute therapy must have been
completed 14 days prior to the time of study entry.
Patients with the following symptoms or conditions are excluded:
Malignancy requiring systemic therapy.
Patients with the following prior conditions are excluded:
- History of acute or chronic pancreatitis.
- History of generalized peripheral neuropathy.
- Inability to tolerate ddI at 200-400 mg/day or d4T at 60-80 mg/day. For purposes of
this study, intolerance will be defined as the same recurrent toxicities requiring
dose interruptions and dose reductions or permanent discontinuation of the drugs
(other than Grade 3 or 4 anemia).
Antiretroviral therapy. If antiretroviral-experienced, no prior NNRTI's or HU and no more
than 12 weeks experience with ddI and/or d4T. Protease inhibitor experience is allowed.
Experienced patients must be on a stable antiretroviral therapy 30 days prior to study
screening and continue this regimen until study entry.
Current ethanol abuse by personal history or a report from a primary physician.