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

NCT00001087 | Completed Phase 2

• 2 other identifiers: ACTG 36410691
• Study Type: interventional
• Target: 300
• Locations: 2 countries
• Sites: 6

Brief 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.)

Conditions

HIV Infections

Keywords

Drug Therapy, Combination; Antiviral Agents; HIV Protease Inhibitors; Ritonavir; Saquinavir; Nelfinavir; Reverse Transcriptase Inhibitors; Adenine; Anti-HIV Agents; efavirenz

Interventions

Ritonavir DRUG

Nelfinavir mesylate DRUG

Efavirenz DRUG

Levocarnitine DRUG

Adefovir dipivoxil DRUG

Saquinavir DRUG

Lamivudine DRUG

Stavudine DRUG

Zidovudine DRUG

Zalcitabine DRUG

Didanosine DRUG

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (6)

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Cook County Hosp. CORE Ctr.

Chicago, Illinois, 60612, United States

Location

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, 60612, United States

Location

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21287, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, United States

Location

Puerto Rico-AIDS CRS

San Juan, 009365067, Puerto Rico

Location

Related Publications (5)

• Albrecht MA, Bosch RJ, Hammer SM, Liou SH, Kessler H, Para MF, Eron J, Valdez H, Dehlinger M, Katzenstein DA; AIDS Clinical Trials Group 364 Study Team. Nelfinavir, efavirenz, or both after the failure of nucleoside treatment of HIV infection. N Engl J Med. 2001 Aug 9;345(6):398-407. doi: 10.1056/NEJM200108093450602.

  PMID: 11496850 BACKGROUND

• Albrecht M, Hammer S, Liou S, Bosch R, Katzenstein D. Long-term virologic and immune responses in subjects maintained on exclusive nucleoside analog (NRTI)based therapy in ACTG 364. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 322)

  BACKGROUND

• Katzenstein DA, Bosch RJ, Hellmann N, Wang N, Bacheler L, Albrecht MA; ACTG 364 Study Team. Phenotypic susceptibility and virological outcome in nucleoside-experienced patients receiving three or four antiretroviral drugs. AIDS. 2003 Apr 11;17(6):821-30. doi: 10.1097/00002030-200304110-00007.

  PMID: 12660529 BACKGROUND

• Winters MA, Bosch RJ, Albrecht MA, Katzenstein DA; AIDS Clinical Trials Group 364 Study Team. Clinical impact of the M184V mutation on switching to didanosine or maintaining lamivudine treatment in nucleoside reverse-transcriptase inhibitor-experienced patients. J Infect Dis. 2003 Aug 15;188(4):537-40. doi: 10.1086/377742. Epub 2003 Jul 24.

  PMID: 12898440 BACKGROUND

• Bosch RJ, Downey GF, Katzenstein DA, Hellmann N, Bacheler L, Albrecht MA; ACTG 364 Study Team. Evaluation of cutpoints for phenotypic hypersusceptibility to efavirenz. AIDS. 2003 Nov 7;17(16):2395-6. doi: 10.1097/00002030-200311070-00016. No abstract available.

  PMID: 14571193 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Interventions

Ritonavir; Nelfinavir; efavirenz; Carnitine; adefovir dipivoxil; Saquinavir; Lamivudine; Stavudine; Zidovudine; Zalcitabine; Didanosine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Quinolines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Thymidine; Inosine; Purine Nucleosides; Purines; Ribonucleosides

Study Officials

• Mary Albrecht

  STUDY CHAIR

• David Katzenstein

  STUDY CHAIR

• Scott Hammer

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: DOUBLE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: July 1, 2000
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

US (5); PR (1)