A Phase II, Randomized Study of the Antiviral Activity and Resistance Interactions of Lamivudine (3TC) in Combination With Zidovudine (AZT), Stavudine (d4T), or Didanosine (ddI) Versus Monotherapy With ddI or d4T in HIV-Infected Individuals With 200 - 600 CD4+ Cells/mm3 and No Previous Nucleoside Experience

Antiviral Activity of and Resistance to Lamivudine in Combination With Zidovudine, Stavudine, or Didanosine

Sponsors

Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Source National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

To evaluate the efficacy, safety, and pharmacokinetics of lamivudine (3TC) combined with zidovudine (AZT), stavudine (d4T), or didanosine (ddI) in comparison with d4T or ddI monotherapy in HIV-infected patients with no prior nucleoside therapy.

3TC may be uniquely effective in combination with AZT due to the interaction of AZT and 3TC resistance mutations. One explanation is that the M184V mutation, which confers resistance to 3TC, suppresses AZT resistance. This benefit of 3TC may not extend to combination therapy with other nucleoside analogs.

Detailed Description

3TC may be uniquely effective in combination with AZT due to the interaction of AZT and 3TC resistance mutations. One explanation is that the M184V mutation, which confers resistance to 3TC, suppresses AZT resistance. This benefit of 3TC may not extend to combination therapy with other nucleoside analogs.

Patients are randomized to either a ddI limb or d4T limb, then randomized a second time to one of six treatment arms, as follows: ddI alone, d4T alone, 3TC/AZT (on both ddI and d4T limbs), 3TC/ddI, and 3TC/d4T. Treatment is given for 48 weeks. At study week 24, patients on monotherapy will have 3TC added to their regimen (in a blinded fashion).

PER AMENDMENT 10/18/96: A treatment extension phase has been added to the study design in order to allow subjects who complete 48 weeks of therapy to remain on their same blinded treatment until approximately 2 months after the last enrolled subject completes 48 weeks on the study.

Overall Status Completed
Completion Date March 1998
Phase Phase 2
Study Type Interventional
Enrollment 256
Condition
Intervention

Intervention type: Drug

Intervention name: Lamivudine

Intervention type: Drug

Intervention name: Stavudine

Intervention type: Drug

Intervention name: Zidovudine

Intervention type: Drug

Intervention name: Didanosine

Eligibility

Criteria:

Inclusion Criteria

Concurrent Medication:

Allowed:

- PCP prophylaxis.

Patients must have:

- HIV infection.

- CD4 count 200 - 600 cells/mm3.

- Life expectancy of at least 24 weeks.

- Consent of parent or guardian if less than 18 years old.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

- Unexplained temperature >= 38.5 C for 7 consecutive days within 30 days prior to study entry.

PER AMENDMENT 1/25/96:

- A malignancy that requires systemic chemotherapies other than Kaposi's sarcoma.

Concurrent Medication:

Excluded:

- Concurrent other antiretroviral or immunologic agents.

- Other experimental therapies.

- Systemic corticosteroids (except as adjuvant therapy for acute PCP) and other immunosuppressive drugs.

- Systemic cytotoxic chemotherapy.

- Induction or maintenance with foscarnet or ganciclovir (oral or IV).

Patients with the following prior conditions are excluded:

- History of acute or chronic pancreatitis.

- History of grade 2 or higher peripheral neuropathy.

Prior Medication:

Excluded:

- Antiretrovirals within 90 days prior to study entry.

- More than 7 days total lifetime use of any antiretroviral nucleoside.

Gender: All

Minimum age: 12 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Location
facility
Alabama Therapeutics CRS | Birmingham, Alabama, United States
UCLA CARE Center CRS | Los Angeles, California, 90095, United States
Stanford CRS | Palo Alto, California, 94115, United States
Ucsd, Avrc Crs | San Diego, California, 92103, United States
Santa Clara Valley Med. Ctr. | San Jose, California, 95128, United States
San Mateo County AIDS Program | San Mateo, California, United States
University of Colorado Hospital CRS | Aurora, Colorado, 80262, United States
Univ. of Miami AIDS CRS | Miami, Florida, 33136, United States
Queens Med. Ctr. | Honolulu, Hawaii, 96816, United States
Univ. of Hawaii at Manoa, Leahi Hosp. | Honolulu, Hawaii, 96816, United States
Cook County Hosp. CORE Ctr. | Chicago, Illinois, 60612, United States
Rush Univ. Med. Ctr. ACTG CRS | Chicago, Illinois, 60612, United States
Weiss Memorial Hosp. | Chicago, Illinois, 60640, United States
Northwestern University CRS | Chicago, Illinois, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic | Indianapolis, Indiana, 46202, United States
Methodist Hosp. of Indiana | Indianapolis, Indiana, 46202, United States
Johns Hopkins Adult AIDS CRS | Baltimore, Maryland, 21287, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS | Boston, Massachusetts, United States
St. Louis ConnectCare, Infectious Diseases Clinic | St Louis, Missouri, 63112, United States
Washington U CRS | St. Louis, Missouri, United States
SUNY - Buffalo, Erie County Medical Ctr. | Buffalo, New York, 14215, United States
Beth Israel Med. Ctr. (Mt. Sinai) | New York, New York, 10003, United States
NYU Med. Ctr., Dept. of Medicine | New York, New York, 10016, United States
Univ. of Rochester ACTG CRS | Rochester, New York, United States
Unc Aids Crs | Chapel Hill, North Carolina, United States
Carolinas HealthCare System, Carolinas Med. Ctr. | Charlotte, North Carolina, United States
Regional Center for Infectious Disease, Wendover Medical Center CRS | Greensboro, North Carolina, United States
MetroHealth CRS | Cleveland, Ohio, 44109, United States
The Ohio State University Medical Center | Columbus, Ohio, 43210, United States
Hosp. of the Univ. of Pennsylvania CRS | Philadelphia, Pennsylvania, 19104, United States
University of Washington AIDS CRS | Seattle, Washington, 98122, United States
Puerto Rico-AIDS CRS | San Juan, Puerto Rico
Location Countries

Puerto Rico

United States

Verification Date

July 2013

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Study Design Info

Primary purpose: Treatment

Source: ClinicalTrials.gov