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

• ClinicalTrials.gov Identifier: NCT00000838
• Recruitment Status: Completed
• First Posted: August 31, 2001
• Last Update Posted: July 29, 2013
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information

• First Submitted Date: November 2, 1999
• First Posted Date: August 31, 2001
• Last Update Posted Date: July 29, 2013
• Study Start Date: Not Provided
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures: Not Provided
• Original Primary Outcome Measures: Not Provided
• Change History: Complete list of historical versions of study NCT00000838 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Antiviral Activity of and Resistance to Lamivudine in Combination With Zidovudine, Stavudine, or Didanosine
• 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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Primary Purpose: Treatment
• Condition: HIV Infections

Intervention

• Drug: Lamivudine
• Drug: Stavudine
• Drug: Zidovudine
• Drug: Didanosine

• Study Arms: Not Provided

Publications *

• Marschner I, Betensky RA, Degruttola V, Kuritzkes DR. Biases in the assessment of viral load reduction in HIV clinical trials. Int Conf AIDS. 1998;12:802 (abstract no 42149)
• Hill A, Demasi R, Kuhn M. Different analyses give highly variable estimates of HIV-1 RNA undetectability and log reduction in clinical trials. Int Conf AIDS. 1998;12:813-4 (abstract no 42204)
• Kuritzkes DR, Marschner IC, Johnson VA, Bassett RL, Eron JJ, Fischl MA, Boone G, Skovronski J, Wood K, Bell DL, Pettinelli CB, Sommadossi JP. A randomized, double-blind, placebo-controlled trial of lamivudine (3TC) in combination with zidovudine (ZDV), stavudine (d4T), or didanosine (ddI) in treatment naive patients. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:79 (abstract no 1)
• Kuritzkes DR, Marschner I, Johnson VA, Bassett R, Eron JJ, Fischl MA, Murphy RL, Fife K, Maenza J, Rosandich ME, Bell D, Wood K, Sommadossi JP, Pettinelli C. Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group Protocol 306 Investigators. AIDS. 1999 Apr 16;13(6):685-94.
• Kuritzkes DR, Bassett RL, Hazelwood JD, Barrett H, Rhodes RA, Young RK, Johnson VA; Adult ACTG Protocol 306 370 Teams. Rate of thymidine analogue resistance mutation accumulation with zidovudine- or stavudine-based regimens. J Acquir Immune Defic Syndr. 2004 May 1;36(1):600-3.
• Fisher M. Nucleoside combinations for antiretroviral therapy: efficacy of stavudine in combination with either didanosine or lamivudine. AIDS. 1998;12 Suppl 3:S9-16.

Recruitment Information

• Recruitment Status: Completed
• Enrollment (submitted: June 23, 2005): 256
• Original Enrollment: Same as current
• Actual Study Completion Date: March 1998
• Primary Completion Date: Not Provided

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT00000838
• Other Study ID Numbers: ACTG 306; 11281 ( Registry Identifier: DAIDS ES Registry Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• Study Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Not Provided

Investigators

• Study Chair: Kuritzkes D
• Study Chair: Johnson V

• PRS Account: National Institute of Allergy and Infectious Diseases (NIAID)
• Verification Date: July 2013