Comparison of Three Different Initial Treatments Without Protease Inhibitors for HIV Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00013520
First received: March 16, 2001
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to compare the effectiveness, safety, and tolerability of 3 anti-HIV combination treatments that do not use protease inhibitors (PIs).

The current rule for starting treatment of HIV infection is to combine members from different classes of anti-HIV drugs, such as 2 nucleoside reverse transcriptase inhibitors (NRTIs) and either a PI or a nonnucleoside reverse transcriptase inhibitor (NNRTI). However, these combinations can be complicated and difficult to take, can cause a number of side effects, and may become ineffective. Combinations that are simpler, better tolerated, and more effective are needed. Because PIs can cause long-term side effects and because HIV can become resistant to many of them at the same time, anti-HIV combination treatments that do not use PIs are being tested.


Condition Intervention Phase
HIV Infections
Drug: Abacavir sulfate, Lamivudine and Zidovudine
Drug: Atazanavir
Drug: Lamivudine/Zidovudine
Drug: Abacavir sulfate
Drug: Efavirenz
Drug: Nevirapine
Drug: Lamivudine
Drug: Stavudine
Drug: Zidovudine
Drug: Didanosine
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
Official Title: Phase III, Randomized, Double-Blind Comparison of Three Protease Inhibitor-Sparing Regimens for the Initial Treatment of HIV Infection

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 1125
Study Completion Date: June 2005
Detailed Description:

Current treatment guidelines recommend combination regimens of 2 nucleoside analogues with either a PI or an NNRTI for the initial treatment of HIV infection. However, the efficacy of current regimens is limited by their complexity, pharmacokinetic characteristics, short- and long-term side effects, and drug-resistance profiles at the time of virologic failure. Consequently, the identification of new initial regimens that are simpler, better tolerated, preserve treatment options in the event of failure, and improve antiretroviral potency is needed. In addition, recent concern over the long-term toxicities of PIs and the extensive cross-resistance among the available PIs have led to the testing of PI-sparing regimens.

Participants will be in this study for a minimum of 120 weeks and a maximum of approximately 4 years. In Step 1, patients are randomly selected to receive 1 of 3 blinded treatment regimens: abacavir (ABC)/lamivudine (3TC)/zidovudine (ZDV)/efavirenz (EFV), ABC/3TC/ZDV, or 3TC/ZDV/EFV. Patients with confirmed virologic failure on Step 1 and two successive plasma HIV RNA levels of 10,000 copies/ml or greater must register to Step 2. Patients with confirmed virologic failure on Step 1 and whose plasma HIV RNA is under 10,000 copies/ml may remain on Step 1 or register to Step 2. [AS PER AMENDMENT 04/11/03: Discontinuation of Arm B was recommended. Consequently, Arms A and C were unblinded to EFV but not to ABC. A number of options are available for patients originally randomized to Arm B.]

Step 2 is open label. Regimens include 2 or 3 nucleoside reverse transcriptase inhibitors (NRTIs) in combination with EFV, atazanavir (ATZ), ritonavir-boosted ATZ, or tenofovir disoproxil fumarate (TDF). Patients on Arm B treatment who have an HIV RNA level less than 200 copies/ml within the past 8 weeks are eligible for randomization to open-label intensification of Arm B on Step 3.

Step 3 regimens include ABC/3TC/ZDV plus either EFV or TDF. Patients with evidence of treatment-limiting toxicity to Step 3 study drugs have the option of substituting d4T for ZDV, ddI for ABC or TDF, and/or NVP for EFV. Patients with confirmed virologic failure on Step 3 and whose plasma HIV RNA is less than 10,000 copies/ml may either remain on Step 3 or register to Step 4. Patients with two successive plasma HIV RNA levels of 10,000 copies/ml or greater on Step 3 must register to Step 4.

Step 4 is open label. Regimens include two or three NRTIs plus EFV, ATV, ritonavir-boosted ATV, or TDF. Clinical assessments and laboratory evaluations are done at entry, at Weeks 2, 4, 6, 8, 12, 16, 20, 24, and then every 8 weeks thereafter for the duration of the study. Evaluations are also required when a protocol-allowed drug substitution is made.

In addition, 3 substudies are being conducted: a neurology substudy for efavirenz, a pharmacology substudy for atazanavir, and a viral dynamics substudy.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

  • Are HIV-positive.
  • Have a viral load of at least 400 copies/ml within 90 days prior to study entry.
  • Are at least 16 years old.
  • Weigh at least 40 kg.
  • Have a negative pregnancy test within 48 hours before starting study drugs, if female and able to have children.
  • Agree to use 2 effective methods of birth control while taking, and for 3 months after stopping, the study medications.
  • Provide written consent of a parent or guardian, if under 18 years of age.

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Have taken anti-HIV drugs in the past.
  • Are allergic to any of the study drugs or ingredients.
  • Are pregnant or breast-feeding.
  • Have taken any of the following drugs within 14 days prior to study entry: amiodarone, astemizole, bepridil, cisapride, ergot or ergot derivatives, systemic itraconazole, systemic ketoconazole, midazolam, propoxyphene, quinidine, rifampin, terfenadine, thalidomide, triazolam, or St. John's wort.
  • Have taken drugs that influence the immune system, HIV or other vaccines, or investigational drugs within 30 days prior to study entry. Prednisone at a dose of 10 mg or less daily is allowed.
  • Have taken drugs or been hospitalized for serious infections or medical illnesses within 14 days prior to study entry.
  • Have growths or tumors that require drug therapy.
  • Have Pneumocystis carinii pneumonia that is not clinically stable and whose treatment is not completed at least 7 days prior to study entry.
  • Have infections or medical illnesses that are not under control or that have not received complete treatment before study entry.
  • Have any condition that, in the opinion of the investigator, would prevent them from properly participating in the study.
  • Abuse drugs or alcohol.
  • This study has been updated to exclude patients who are receiving systemic itraconazole and rifabutin.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00013520

  Show 60 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Roy Gulick, MD
Study Chair: Cecilia Shikuma, MD
  More Information

Additional Information:
Publications:
H Ribaudo, D Clifford, R Gulick, C Shikuma, K Klingman, S Snyder, and E Acosta. Relationships between Efavirenz Pharmacokinetics, Side Effects, Drug Discontinuation, Virologic Response, and Race: Results from ACTG A5095/A5097s. CROI 2004. Abstract 132.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00013520     History of Changes
Other Study ID Numbers: A5095, 10212, ACTG A5095, AACTG A5095, Substudy ACTG A5097s, Substudy AACTG 5107s, Substudy AACTG 5166s, Substudy ACTG A5166s, Substudy AACTG 5097s, Substudy ACTG A5107s, 5-K24-AI051966-03
Study First Received: March 16, 2001
Last Updated: May 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV-1
Didanosine
Drug Therapy, Combination
Zidovudine
Nevirapine
Stavudine
Lamivudine
RNA, Viral
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
Combivir
BMS 232632
Efavirenz
Treatment Naive

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Communicable Diseases
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Abacavir
Didanosine
Dideoxynucleosides
Efavirenz
HIV Protease Inhibitors
Lamivudine
Lamivudine, zidovudine drug combination
Nevirapine
Protease Inhibitors
Reverse Transcriptase Inhibitors
Stavudine
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents

ClinicalTrials.gov processed this record on October 29, 2014