The Effectiveness of Nelfinavir and Efavirenz, Used Alone or Together, Combined With Other Anti-HIV Drugs in Patients Who Have Taken Anti-HIV Drugs

• Status: Completed
• Trial end date: 2000-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Steps I and II: The purpose of this study is the following: To look at how many patients achieve undetectable HIV blood levels at Week 16. To look at the absolute change in HIV blood levels from the beginning of the study to Week 16. To look at the safety and tolerability of nelfinavir (NFV) and efavirenz (EFV) when used in combination or separately in regimens containing reverse transcriptase inhibitors (RTIs). For the 2 extension studies (Weeks 49 to 144): To look at the proportion of patients whose long-term viral load remains undetectable at Week 96. To look at the time from the beginning of the study to treatment failure, with patients evaluated through Week 144. Step III: To look at the proportion of patients whose HIV blood levels are undetectable 16 weeks after starting the salvage study treatment. To assess safety, toxicity, and tolerance of salvage study drug treatment. (This study has been changed by adding new objectives.) Achieving viral suppression has been widely endorsed as the primary goal of HIV therapy. However, there are few established guidelines for devising combinations of different classes of drugs which will enhance the potential for achieving viral suppression, reducing the risk of toxicity, and preserving therapeutic options for future use. This study includes 2 anti-HIV drugs, NFV (a protease inhibitor [PI]) and EFV (a nonnucleoside reverse transcriptase inhibitor [NNRTI]), for use either alone or in combination with RTI therapy for the purpose of limiting HIV replication. Patients with treatment failure at Week 16 choose 1 of the following 3 alternative salvage therapies: 2-drug PI regimen (saquinavir and ritonavir) plus adefovir dipivoxil and L-carnitine; EFV or NFV (if not already given) plus 2 new approved anti-HIV drugs outside the study; or the best available treatment outside the study. The new RTI, adefovir dipivoxil, is added to the 2-drug PI regimen to achieve suppression of viral replication and thereby delay disease progression. (This rationale reflects a change in the treatment given to patients with treatment failure at Week 16.)

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Adefovir; Adefovir dipivoxil; Didanosine; Efavirenz; Lamivudine; Nelfinavir; Ritonavir; Saquinavir; Stavudine; Zalcitabine; Zidovudine

Criteria

Inclusion Criteria

Concurrent Medication:

Required:

• Chemoprophylaxis for Pneumocystis carinii pneumonia for all patients who have a CD4 count of 200 cells/mm3 or less.

Allowed:

• Topical and oral antifungal except for oral ketoconazole.

• Treatment, maintenance, or chemoprophylaxis with approved agents for opportunistic infections as clinically indicated.

• All antibiotics as clinically indicated.

• Systemic corticosteroid use for no more than 21 days for acute problems as medically indicated. Note: Steroid use for more than 21 days is considered on a case-by-case basis.

• Recombinant erythropoietin (rEPO) and granulocyte colony-stimulating factor (G-CSF) as medically indicated.

• Regularly prescribed medications such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives, megestrol acetate, testosterone, or any other medications as medically indicated.

[AS PER AMENDMENT 4/25/00:

Allowed with caution:

• Pentamidine, allopurinol, hydroxyurea. Use of these medications may increase exposure to ddI.]

Concurrent Treatment:

Allowed:

• Dependency of less than 3 units of blood per 21-day period.

• Alternative therapies such as acupuncture and visualization techniques.

Patients must have:

• HIV infection documented by a licensed ELISA and confirmed by Western blot, positive HIV culture, positive HIV antigen, positive plasma HIV RNA, or second antibody test positive by a method other than ELISA. Repeat HIV-antibody testing is not required for enrollment in this trial (implicit in patients having been enrolled in ACTG 302/303).

• Signed, informed consent from parent or legal guardian for patients under 18 years of age.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Inability to tolerate ddI at 200-400 mg/day, 3TC at 300 mg/day, or d4T at 60-80 mg/day, with intolerance defined as recurrent toxicities requiring dose interruptions and reductions or permanent discontinuation of the drugs (other than Grade 3 or 4 anemia).

• Grade 2 or higher peripheral neuropathy.

• Malignancy requiring systemic therapy.

• Co-enrollment in other antiretroviral protocols; co-enrollment in other ACTG protocols is encouraged, particularly those involving prophylaxis for opportunistic infections.

Concurrent Medication:

Excluded:

• All antiretroviral therapies other than study medications.

• Investigational drugs and vaccines without specific approval from the Protocol Chair/Vice Chairs.

• Systemic cytotoxic chemotherapy.

• Interferon, interleukins, GM-CSF, and HIV-1 vaccines.

• Rifabutin and rifampin.

• Ketoconazole, astemizole, cisapride, midazolam, terfenadine, and triazolam.

• Acute therapy for an infection or other medical illness.

• Herbal medications.

• Vitamins. [10. AS PER AMENDMENT 3/5/98:

• Ergot alkaloids or drugs containing derivatives or ergot alkaloids.]

Patients with the following prior conditions are excluded:

• History of acute or chronic pancreatitis.

Prior Medication:

Excluded:

• PIs.

• NNRTIs.

• Acute therapy for an infection or other medical illness within 14 days prior to the time of study entry.

• Chronic long-term steroid use is not permitted unless it is within physiologic replacement levels; protocol chair/vice chairs must be contacted in these instances.

Risk Behavior:

Excluded:

• Current ethanol abuse by personal history or a report from a primary physician.