Immunologic and Virologic Consequences of Long-Term Highly Active Antiretroviral Therapy (HAART) in Subjects With Moderately Advanced HIV-1 Disease: A Follow-Up Study to ACTG 315

NCT00000891 | Completed Phase 2

• 3 other identifiers: ACTG 375Substudy ACTG A5002s11336
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 3

Brief Summary

To evaluate the relationship between viral suppression and changes in immune function, as measured by the restoration of delayed-type hypersensitivity (DTH) and lymphoproliferative (LP) responses, observed after 48 weeks of treatment with highly active antiretroviral therapy (HAART) in ACTG 315. To evaluate the durability of the antiviral and immunologic effects of long-term treatment with HAART. Given the extensive immunologic and virologic data available from ACTG 315, follow-up studies of this advanced-disease population are indicated to primarily ascertain the impact of long-term suppression of viral replication on immunologic reconstitution or re-education and the durability of the antiviral effects of HAART.

Conditions

HIV Infections

Keywords

Drug Therapy, Combination; Hypersensitivity, Delayed; Follow-Up Studies; Anti-HIV Agents; Viral Load

Interventions

Ritonavir DRUG

Saquinavir DRUG

Delavirdine mesylate DRUG

Lamivudine DRUG

Stavudine DRUG

Zidovudine DRUG

Didanosine DRUG

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Concurrent Medication:
• Allowed:
• Protocol Chair-approved antiretroviral medications or research study treatment for an HIV complication.
• Treatment, maintenance, or chemoprophylaxis with approved medications for opportunistic infections.
• Antibiotics.
• Recombinant erythropoietin (rEPO) and granulocyte colony-stimulating factor (G-CSF, filgrastim).
• Regularly prescribed medications, such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives (not as a sole form of birth control), megestrol acetate, testosterone, or any other medication not explicitly excluded.
• Alternative therapies such as vitamins, acupuncture, and visualization techniques.
• Patients must have:
• HIV-positive status.
• Completion of 48 weeks of study treatment in ACTG 315 and maintenance in this regimen (on-study) until enrollment in this study.
• Signed, informed consent from parent or legal guardian for patients less than 18 years of age.

You may not qualify if:

• Co-existing Condition:
• Patients with the following conditions and symptoms are excluded:
• Documented or suspected pancreatitis or hepatitis within 2 weeks prior to study entry.
• Concurrent Medication:
• Excluded:
• Immunomodulators that affect immunologic or virologic indices (e.g., systemic corticosteroids, thalidomide, cytokines).
• Ketoconazole, rifampin, and rifabutin.
• Amiodarone, astemizole, bepridil, bupropion, cisapride, clozapine, dihydroergotamine, encainide, ergotamine, flecainide, meperidine, pimozide, piroxicam, propafenone, propoxyphene, quinidine, terfenadine, alprazolam, clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam, zolpidem, phenytoin, phenobarbital, and carbamazepine.
• \[AS PER AMENDMENT 3/5/01:
• Lovastatin and simvastatin.
• Excluded for patients who are pregnant:
• ddI or d4T.\]
• Avoided:
• Herbal medications.
• \[2. AS PER AMENDMENT 4/10/00:

Sponsors & Collaborators

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

Study Sites (3)

Univ of Colorado Health Sciences Ctr

Denver, Colorado, 80262, United States

Location

Rush Presbyterian - Saint Luke's Med Ctr

Chicago, Illinois, 60612, United States

Location

Case Western Reserve Univ

Cleveland, Ohio, 44106, United States

Location

Related Publications (6)

• Smith KY, Valdez H, Landay A, Spritzler J, Kessler HA, Connick E, Kuritzkes D, Gross B, Francis I, McCune JM, Lederman MM. Thymic size and lymphocyte restoration in patients with human immunodeficiency virus infection after 48 weeks of zidovudine, lamivudine, and ritonavir therapy. J Infect Dis. 2000 Jan;181(1):141-7. doi: 10.1086/315169.

  PMID: 10608760 BACKGROUND

• Valdez H, Connick E, Lederman M, Smith K, Fox L, St. T-lymphocyte changes after 3 years of controlled viral replication. Clair M, Bosch R, Kim R, Blanchard M, Landay A. 8th Conf Retro and Opportun Infect 2001 Feb 4-8 (abstract no 372)

  BACKGROUND

• Valdez H, Smith KY, Landay A, Connick E, Kuritzkes DR, Kessler H, Fox L, Spritzler J, Roe J, Lederman MB, Lederman HM, Evans TG, Heath-Chiozzi M, Lederman MM. Response to immunization with recall and neoantigens after prolonged administration of an HIV-1 protease inhibitor-containing regimen. ACTG 375 team. AIDS Clinical Trials Group. AIDS. 2000 Jan 7;14(1):11-21. doi: 10.1097/00002030-200001070-00002.

  PMID: 10714563 BACKGROUND

• Valdez H, Smith K, Lederman M, Landay A, Kessler H, Connick E, Kuritzkes D, Spritzler J, Fox L, Roe J, Lederman H, Lederman MB, Evans T. Response to immunization with recall and neoantigens after 48 weeks of HAART. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:130 (abstract no 329)

  BACKGROUND

• Smith KY, Valdez H, Landay A, Connick E, Gross B, Wade M, Lederman M. Correlations between immunologic indices and thymic mass in HIV infected patients following 48 weeks of therapy with zidovudine, lamivudine and ritonavir (ZLR). Int Conf AIDS. 1998;12:264 (abstract no 21129)

  BACKGROUND

• Wu H, Connick E, Kuritzkes DR, Landay A, Spritzler J, Zhang B, Spear GT, Kessler H, Lederman MM; ACTG 315 Team. Multiple CD4+ cell kinetic patterns and their relationships with baseline factors and virological responses in HIV type 1 patients receiving highly active antiretroviral therapy. AIDS Res Hum Retroviruses. 2001 Sep 1;17(13):1231-40. doi: 10.1089/088922201750461285.

  PMID: 11559422 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Hypersensitivity, Delayed

Interventions

Ritonavir; Saquinavir; Delavirdine; Lamivudine; Stavudine; Zidovudine; 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; Hypersensitivity

Intervention Hierarchy (Ancestors)

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

Study Officials

• Hernan Valdez

  STUDY CHAIR

• Kimberly Smith

  STUDY CHAIR

• Michael Lederman

  STUDY CHAIR

• Harold Kessler

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: May 1, 2004
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

US (3)