Clinical trial NCT00001025: Evaluation of Patients Who Have Not Had Success With Zidovudine
Official title: A Study to Evaluate the Short-Term Clinical and Virologic Significance of Zidovudine Resistance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Virus Replication
Didanosine
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Bristol-Myers Squibb
name: Glaxo Wellcome
First posted: 2001-08-31
Enrollment: 120
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: San Francisco Gen Hosp
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
state: California
city: Stanford
country: United States
facility: San Mateo AIDS Program / Stanford Univ
state: California
city: Denver
country: United States
facility: Kaiser Permanente Franklin Med Ctr
state: Colorado
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: Chicago
country: United States
facility: Children's Mem Hosp Family Cln / Northwestern Univ Med Schl
state: Illinois
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Springfield
country: United States
facility: Baystate Med Ctr of Springfield
state: Massachusetts
city: Minneapolis
country: United States
facility: Univ of Minnesota
state: Minnesota
city: Omaha
country: United States
facility: Univ of Nebraska Med Ctr
state: Nebraska
city: Brooklyn
country: United States
facility: SUNY / Health Sciences Ctr at Brooklyn
state: New York
city: Buffalo
country: United States
facility: SUNY / Erie County Med Ctr at Buffalo
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY / State Univ of New York
state: New York
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
Study officials:
name: Corey L
role: STUDY_CHAIR
name: Cavert W
role: STUDY_CHAIR
name: Coombs R
role: STUDY_CHAIR
References:
citation: 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
citation: 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)