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The Effects of Anti-HIV Drugs in HIV-Infected Patients Who Do Not Have AIDS

Primary Purpose

HIV Infections

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Zidovudine
Didanosine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Didanosine, AIDS-Related Complex, Zidovudine, Lymph Nodes, Lymphoid Tissue

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Allowed: Chemoprophylaxis against M. tuberculosis, therapy for oral candidiasis, and short courses (up to 10 days) of acyclovir for herpes lesions. Antibiotics as clinically indicated. Pneumococcal vaccine and hepatitis B vaccine as medically indicated. Regularly prescribed medications such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives, or other medications deemed appropriate by the patient's primary care provider. Recommended: PCP prophylaxis if patient's CD4 count falls below 200 cells/mm3 during the study. Concurrent Treatment: Allowed: Alternative therapies such as vitamins and acupuncture. Patients must have: Documented HIV infection. At least two palpable lymph nodes above the waist. CD4 counts >= 350 cells/mm3 (if previously antiretroviral-naive) or >= 250 cells/mm3 (if receiving ongoing AZT therapy). Patients with prior AZT therapy must have received a stable dose of 300-600 mg daily for 26 or more weeks. Prior Medication: Required in patients with prior ongoing therapy: AZT at dose of 300-600 mg daily for at least 26 weeks. Exclusion Criteria Co-existing Condition: Patients with the following symptoms and conditions are excluded: Severe malabsorption. Current AIDS-related opportunistic infection, AIDS dementia, AIDS-wasting syndrome, or an AIDS-related malignancy other than minimal Kaposi's sarcoma disease. Current medical problems that may interfere with the evaluation of AZT or increase the potential toxicity of AZT (e.g., significant liver disease, diabetes, significant cardiovascular disease, seizure disorders, lymphoma, acute or chronic pancreatitis, or febrile illness). Current diagnosis of malignancy for which systemic therapy would be required during study. Concurrent Medication: Excluded: Ganciclovir, foscarnet, chronic acyclovir, or probenecid. Other proven or alleged antiretroviral or anti-HIV drugs. Biologic response modifiers. Valproic acid. Systemic cytotoxic chemotherapy. Steroids. Concurrent Treatment: Excluded: Radiation therapy. Patients with the following prior conditions are excluded: Prior AIDS-related opportunistic infection, AIDS dementia, AIDS-wasting syndrome, or an AIDS-related malignancy other than minimal Kaposi's sarcoma disease. History of medical problems that may interfere with the evaluation of AZT or increase the potential toxicity of AZT (e.g., significant liver disease, diabetes, significant cardiovascular disease, seizure disorders, lymphoma, acute or chronic pancreatitis, or febrile illness). History of peripheral neuropathy (patients with prior AZT treatment only). Prior Medication: Excluded: Prior ddI therapy. Less than 26 weeks of prior AZT (in patients with ongoing AZT therapy only). Ganciclovir, foscarnet, chronic acyclovir, or probenecid. Cytotoxic chemotherapy within 1 month prior to study entry. Acute therapy for an infection or other medical illness within 14 days prior to study entry. History of alcohol abuse (patients with prior AZT treatment).

Sites / Locations

  • Palo Alto Veterans Affairs Health Care System
  • Kaiser Permanente Med Ctr
  • Mount Zion Med Ctr / UCSF
  • Univ of Illinois
  • Univ of Maryland at Baltimore
  • SUNY / Health Sciences Ctr at Stony Brook
  • Duke Univ Med Ctr
  • Univ of Pittsburgh

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Glaxo Wellcome
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1. Study Identification

Unique Protocol Identification Number
NCT00001024
Brief Title
The Effects of Anti-HIV Drugs in HIV-Infected Patients Who Do Not Have AIDS
Official Title
A Multicenter, Open-Label Study of Viral Burden in Peripheral Blood Versus Lymphoid Tissue Before and After Antiretroviral Therapy in HIV-Infected Individuals Without AIDS (NOTE: One Arm Receives no Treatment)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
June 2002 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Glaxo Wellcome

4. Oversight

5. Study Description

Brief Summary
Immunopathogenesis objectives: To compare and quantitatively determine HIV burden and HIV replication in peripheral blood (PB) and lymphoid tissue (LT). To determine the degree to which antiretroviral therapy alters HIV replication in LT. Clinical objectives: To gain insight into the degree of correlation between immunologic surrogate markers for HIV disease (e.g., CD4, beta-2 microglobulin) as compared to measures of HIV replication in PB and LT. To assess changes in PB and LT viral burden after antiretroviral therapy and to determine its ability to predict an antiviral response. One of the major problems in defining the immunopathogenic changes in HIV infections has been the inability to correlate the extent of loss of immunologic function with the number of HIV-infected CD4+ cells in the peripheral blood. Few studies exist that measure viral burden in lymph nodes of HIV-infected individuals. Researchers hope to find out whether the amount of HIV virus or markers for the virus in the body's lymph tissue is a better measure of disease progression than the amount of virus or markers for the virus in the blood.
Detailed Description
One of the major problems in defining the immunopathogenic changes in HIV infections has been the inability to correlate the extent of loss of immunologic function with the number of HIV-infected CD4+ cells in the peripheral blood. Few studies exist that measure viral burden in lymph nodes of HIV-infected individuals. Researchers hope to find out whether the amount of HIV virus or markers for the virus in the body's lymph tissue is a better measure of disease progression than the amount of virus or markers for the virus in the blood. Sixteen antiretroviral-naive patients are randomized to either remain antiretroviral-naive (no treatment) or receive zidovudine daily (treatment). Additionally, 16 patients with 26 or more weeks of ongoing zidovudine (AZT) therapy are randomized to either continue on their prestudy AZT regimen or add didanosine (ddI) daily to their baseline AZT dose. Patients remain on their assigned treatment arms for 8 weeks. A lymph node biopsy is performed on day 0 and at week 8. Patients are evaluated at weeks 2, 4, 6, 8 and 9.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Didanosine, AIDS-Related Complex, Zidovudine, Lymph Nodes, Lymphoid Tissue

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Enrollment
32 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Didanosine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Chemoprophylaxis against M. tuberculosis, therapy for oral candidiasis, and short courses (up to 10 days) of acyclovir for herpes lesions. Antibiotics as clinically indicated. Pneumococcal vaccine and hepatitis B vaccine as medically indicated. Regularly prescribed medications such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives, or other medications deemed appropriate by the patient's primary care provider. Recommended: PCP prophylaxis if patient's CD4 count falls below 200 cells/mm3 during the study. Concurrent Treatment: Allowed: Alternative therapies such as vitamins and acupuncture. Patients must have: Documented HIV infection. At least two palpable lymph nodes above the waist. CD4 counts >= 350 cells/mm3 (if previously antiretroviral-naive) or >= 250 cells/mm3 (if receiving ongoing AZT therapy). Patients with prior AZT therapy must have received a stable dose of 300-600 mg daily for 26 or more weeks. Prior Medication: Required in patients with prior ongoing therapy: AZT at dose of 300-600 mg daily for at least 26 weeks. Exclusion Criteria Co-existing Condition: Patients with the following symptoms and conditions are excluded: Severe malabsorption. Current AIDS-related opportunistic infection, AIDS dementia, AIDS-wasting syndrome, or an AIDS-related malignancy other than minimal Kaposi's sarcoma disease. Current medical problems that may interfere with the evaluation of AZT or increase the potential toxicity of AZT (e.g., significant liver disease, diabetes, significant cardiovascular disease, seizure disorders, lymphoma, acute or chronic pancreatitis, or febrile illness). Current diagnosis of malignancy for which systemic therapy would be required during study. Concurrent Medication: Excluded: Ganciclovir, foscarnet, chronic acyclovir, or probenecid. Other proven or alleged antiretroviral or anti-HIV drugs. Biologic response modifiers. Valproic acid. Systemic cytotoxic chemotherapy. Steroids. Concurrent Treatment: Excluded: Radiation therapy. Patients with the following prior conditions are excluded: Prior AIDS-related opportunistic infection, AIDS dementia, AIDS-wasting syndrome, or an AIDS-related malignancy other than minimal Kaposi's sarcoma disease. History of medical problems that may interfere with the evaluation of AZT or increase the potential toxicity of AZT (e.g., significant liver disease, diabetes, significant cardiovascular disease, seizure disorders, lymphoma, acute or chronic pancreatitis, or febrile illness). History of peripheral neuropathy (patients with prior AZT treatment only). Prior Medication: Excluded: Prior ddI therapy. Less than 26 weeks of prior AZT (in patients with ongoing AZT therapy only). Ganciclovir, foscarnet, chronic acyclovir, or probenecid. Cytotoxic chemotherapy within 1 month prior to study entry. Acute therapy for an infection or other medical illness within 14 days prior to study entry. History of alcohol abuse (patients with prior AZT treatment).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J Cohn
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
M Niu
Official's Role
Study Chair
Facility Information:
Facility Name
Palo Alto Veterans Affairs Health Care System
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Kaiser Permanente Med Ctr
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Mount Zion Med Ctr / UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Univ of Illinois
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Univ of Maryland at Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
SUNY / Health Sciences Ctr at Stony Brook
City
Stony Brook
State/Province
New York
ZIP/Postal Code
117948153
Country
United States
Facility Name
Duke Univ Med Ctr
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Univ of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States

12. IPD Sharing Statement

Citations:
Citation
Cohen OJ, Pantaleo G, Graziosi C, Niu M, Fauci AS. Effect of antiretroviral therapy on HIV burden and replication in lymphoid tissue. DATRI 003 Study Group. Int Conf AIDS. 1994 Aug 7-12;10(1):7 (abstract no 001B)
Results Reference
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The Effects of Anti-HIV Drugs in HIV-Infected Patients Who Do Not Have AIDS

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