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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000838

Collaborator

(none)

256

Enrollment

Locations

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Lamivudine Drug: Stavudine Drug: Zidovudine Drug: Didanosine	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

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

Actual Study Completion Date :

Mar 1, 1998

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Therapeutics CRS	Birmingham	Alabama	United States
2	UCLA CARE Center CRS	Los Angeles	California	United States	90095
3	Stanford CRS	Palo Alto	California	United States	94115
4	Ucsd, Avrc Crs	San Diego	California	United States	92103
5	Santa Clara Valley Med. Ctr.	San Jose	California	United States	95128
6	San Mateo County AIDS Program	San Mateo	California	United States
7	University of Colorado Hospital CRS	Aurora	Colorado	United States	80262
8	Univ. of Miami AIDS CRS	Miami	Florida	United States	33136
9	Queens Med. Ctr.	Honolulu	Hawaii	United States	96816
10	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii	United States	96816
11	Cook County Hosp. CORE Ctr.	Chicago	Illinois	United States	60612
12	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612
13	Weiss Memorial Hosp.	Chicago	Illinois	United States	60640
14	Northwestern University CRS	Chicago	Illinois	United States
15	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
16	Methodist Hosp. of Indiana	Indianapolis	Indiana	United States	46202
17	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
18	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts	United States
19	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri	United States	63112
20	Washington U CRS	Saint Louis	Missouri	United States
21	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
22	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York	United States	10003
23	NYU Med. Ctr., Dept. of Medicine	New York	New York	United States	10016
24	Univ. of Rochester ACTG CRS	Rochester	New York	United States
25	Unc Aids Crs	Chapel Hill	North Carolina	United States
26	Carolinas HealthCare System, Carolinas Med. Ctr.	Charlotte	North Carolina	United States
27	Regional Center for Infectious Disease, Wendover Medical Center CRS	Greensboro	North Carolina	United States
28	MetroHealth CRS	Cleveland	Ohio	United States	44109
29	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
30	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania	United States	19104
31	University of Washington AIDS CRS	Seattle	Washington	United States	98122
32	Puerto Rico-AIDS CRS	San Juan		Puerto Rico