Evaluation of Patients Who Have Not Had Success With Zidovudine

HIV Infections Clinical Trial

Official title:

A Study to Evaluate the Short-Term Clinical and Virologic Significance of Zidovudine Resistance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001025
• Other study ID #: ACTG 194
• Secondary ID: 11170
• Status: Completed
• Phase: Phase 2
• Est. completion date: May 1995

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine the relationship of viral susceptibility to zidovudine (AZT) and baseline viral load (as determined by plasma viremia and quantitative endpoint dilution). To determine the relationship between viral load and susceptibility during different antiretroviral therapy strategies. To correlate measures of viral load and short term clinical and laboratory markers (such as weight, CD4 count, p24 antigenemia, and beta2 microglobulin) on the different therapy arms.

High-grade resistance to AZT has been detected in HIV isolates from approximately 25 percent of individuals with AIDS who received AZT for at least 1 year. To elucidate the clinical significance of in vitro AZT resistance, it is necessary to distinguish between clinical failure caused by AZT resistance and clinical decompensation caused by other factors.

Description:

High-grade resistance to AZT has been detected in HIV isolates from approximately 25 percent of individuals with AIDS who received AZT for at least 1 year. To elucidate the clinical significance of in vitro AZT resistance, it is necessary to distinguish between clinical failure caused by AZT resistance and clinical decompensation caused by other factors.

One hundred-twenty patients who have been receiving AZT for at least 1 year are randomized to 1) continue with AZT, 2) switch to treatment with didanosine at 1 of 2 doses, or 3) receive both AZT and ddI. Treatment is given for 16 weeks, with a possible extension to 32 weeks. Patients are followed at weeks 2, 4, 8, 12, and 16. For analysis purposes only, patients are stratified according to degree of susceptibility of HIV isolates to AZT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: May 1995
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Chemoprophylaxis against Pneumocystis carinii pneumonia (PCP), Mycobacterium tuberculosis, or Herpes simplex virus, or against other opportunistic infections as indicated.

• Corticosteroids for no longer than 21 days (only as part of PCP therapy).

• Erythropoietin and G-CSF.

Patients must have:

• Documented HIV-seropositivity.

• CD4 count 100 - 300 cells/mm3.

• Prior continuous AZT dose = or > 300 mg/day for 1 year or longer.

Prior Medication: Required:

• AZT for at least 1 year prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Medical contraindication or is considered noncompliant in the opinion of the investigator.

• Peripheral neuropathy = or > grade 2.

Concurrent Medication:

Excluded:

• Anti-HIV agents other than study drugs.

• Biologic response modifiers (other than erythropoietin or G-CSF).

• Systemic cytotoxic chemotherapy.

• Regularly prescribed medications (such as antipyretics, analgesics, allergy medications) that are associated with an increased risk of pancreatitis, peripheral neuropathy, or bone marrow suppression.

Concurrent Treatment:

Excluded:

• Radiation therapy.

Patients with the following prior conditions are excluded:

• History of acute or chronic pancreatitis, gout, or uric acid nephropathy.

Prior Medication:

Excluded:

• Other antiretrovirals besides AZT.

• ddI or ddC for more than 30 days within the past year or any time within 3 months prior to study entry.

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Zidovudine

• Didanosine

Locations

Country	Name	City	State
United States	Univ of Alabama at Birmingham	Birmingham	Alabama
United States	SUNY / Health Sciences Ctr at Brooklyn	Brooklyn	New York
United States	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York
United States	Children's Mem Hosp Family Cln / Northwestern Univ Med Schl	Chicago	Illinois
United States	Cook County Hosp	Chicago	Illinois
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois
United States	Kaiser Permanente Franklin Med Ctr	Denver	Colorado
United States	Univ of Colorado Health Sciences Ctr	Denver	Colorado
United States	Univ of Minnesota	Minneapolis	Minnesota
United States	Univ of Nebraska Med Ctr	Omaha	Nebraska
United States	Univ of Rochester Medical Center	Rochester	New York
United States	San Francisco Gen Hosp	San Francisco	California
United States	Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium	San Jose	California
United States	Univ of Washington	Seattle	Washington
United States	Baystate Med Ctr of Springfield	Springfield	Massachusetts
United States	San Mateo AIDS Program / Stanford Univ	Stanford	California
United States	SUNY / State Univ of New York	Syracuse	New York

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Bristol-Myers Squibb, Glaxo Wellcome

Country where clinical trial is conducted

United States, 

References & Publications (2)

Cavert W, Coombs RW, Kuritzkes D, Grimes J, Stein D, Rojo W, Beatty C, Winters M, Corey L. Baseline zidovudine (ZDV) susceptibility, codon 215 mutation, viral load and syncytium-inducting characteristics(SI) of HIV isolates from ACTG protocol 194. Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16:137

Reichelderfer PS, Coombs RW. Multifactorial analysis of the inverse relationship between viral load and CD4+ cell count. Int Conf AIDS. 1996 Jul 7-12;11(2):277 (abstract no ThB4148)