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Comparison of Three Different Initial Treatments, Not Using Protease Inhibitors, for HIV Infection



Comparison of Three Different Initial Treatments, Not Using Protease Inhibitors, for HIV Infection

For Condition: HIV Infections
Status: No longer recruiting
Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) ,
Synopsis: The purpose of this study is to compare 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: 2 nucleoside reverse transcriptase inhibitors (NRTIs) with 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. Therefore, there is a need for combinations that are simpler, better tolerated, and more effective. 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.
Details: Current treatment guidelines recommend combination regimens of 2 nucleoside analogues with either a PI, a nonnucleoside reverse transcriptase inhibitor (NNRTI), or a triple nucleoside analogue regimen as therapy 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 on 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. 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: Step 2 is open label. Regimens include 2 or 3 nucleoside reverse transcriptase inhibitors (NRTIs) in combination with EFV, atazanavir, 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 BID 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, 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:
Study Type:
  Interventional, Treatment, Active Control, Safety/Efficacy Study
Minimum Age/Maximum Age: 16 Years/
Genders: Both
Protocol Entry 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.
Total Enrollment: 1125

Location and Contact Information:

Overall Study Official:
RoyGulick,  Study Chair, 

Univ of Miami School of Medicine
Miami,  Florida,  331361013
United States
 

Univ of Minnesota
Minneapolis,  Minnesota,  55455
United States
 

Univ of Colorado Health Sciences Ctr
Denver,  Colorado,  80262
United States
 

Indiana Univ Hosp
Indianapolis,  Indiana,  462025250
United States
 

Cornell Univ Med Ctr
New York City,  New York,  10021
United States
 

Univ of Texas Galveston
Galveston,  Texas,  775550435
United States
 

Univ of Cincinnati
Cincinnati,  Ohio,  452670405
United States
 

Univ of California, San Diego
San Diego,  California,  92103
United States
 

Ohio State Univ Hosp Clinic
Columbus,  Ohio,  432101228
United States
 

Univ of Hawaii
Honolulu,  Hawaii,  96816
United States
 

Northwestern Univ Med School
Chicago,  Illinois,  60611
United States
 

Wishard Hosp
Indianapolis,  Indiana,  46202
United States
 

Beth Israel Med Ctr
New York City,  New York,  10003
United States
 

Cornell Clinical Trials Unit - Chelsea Clinic
New York City,  New York,  10011
United States
 

Univ of Washington
Seattle,  Washington,  98104
United States
 

UCLA CARE Ctr
Los Angeles,  California,  90095
United States
 

Harbor UCLA Med Ctr
Torrance,  California,  90502
United States
 

Bellevue Hosp / New York Univ Med Ctr
New York City,  New York,  10016
United States
 

Univ of California, Davis Med Ctr
Sacramento,  California,  95814
United States
 

San Mateo AIDS Program / Stanford Univ
Stanford,  California,  943055107
United States
 

Georgetown Univ Med Ctr
Washington D.C.,  District of Columbia,  20007
United States
 

Aaron Diamond AIDS Rsch Ctr / Rockefeller Univ
New York City,  New York,  10021
United States
 

Univ of Iowa Hosp and Clinic
Iowa City,  Iowa,  52242
United States
 

Duke Univ Med Ctr
Durham,  North Carolina,  27710
United States
 

Univ of Texas, Southwestern Med Ctr of Dallas
Dallas,  Texas,  75390
United States
 

MetroHealth Med Ctr
Cleveland,  Ohio,  441091998
United States
 

Univ of Alabama at Birmingham
Birmingham,  Alabama,  35294
United States
 

Johns Hopkins Hosp
Baltimore,  Maryland,  21287
United States
 

Univ of Pittsburgh
Pittsburgh,  Pennsylvania,  15213
United States
 

The CORE Ctr
Chicago,  Illinois,  60612
United States
 

Univ of North Carolina
Chapel Hill,  North Carolina,  275997215
United States
 

Univ of Southern California / LA County USC Med Ctr
Los Angeles,  California,  900331079
United States
 

Julio Arroyo
West Columbia,  South Carolina,  29169
United States
 

SUNY / Erie County Med Ctr at Buffalo
Buffalo,  New York,  14215
United States
 

Willow Clinic
Menlo Park,  California,  94025
United States
 

Univ of Rochester Medical Center
Rochester,  New York,  14642
United States
 

Brown Univ / Miriam Hosp
Providence,  Rhode Island,  02906
United States
 

Moses H Cone Memorial Hosp
Greensboro,  North Carolina,  27401
United States
 

Emory Univ
Atlanta,  Georgia,  30308
United States
 

Boston Med Ctr
Boston,  Massachusetts,  02118
United States
 

Univ of California San Francisco
San Francisco,  California,  94110
United States
 

Kaiser Permanente LAMC
Los Angeles,  California,  90027
United States
 

Columbia Presbyterian Med Ctr
New York City,  New York,  10032
United States
 

Stanford Univ Med Ctr
Stanford,  California,  943055107
United States
 

Vanderbilt Univ Med Ctr
Nashville,  Tennessee,  37203
United States
 

Univ of Puerto Rico
San Juan,  ,  009365067
Puerto Rico
 

Univ of Pennsylvania
Philadelphia,  Pennsylvania,  19104
United States
 

Beth Israel Deaconess - West Campus
Boston,  Massachusetts,  02215
United States
 

Miriam Hosp / Brown Univ
Providence,  Rhode Island,  02906
United States
 

Rush Presbyterian - Saint Luke's Med Ctr
Chicago,  Illinois,  60612
United States
 

Philadelphia Veterans Administration Med Ctr
Philadelphia,  Pennsylvania,  19104
United States
 

Harvard (Massachusetts Gen Hosp)
Boston,  Massachusetts,  02114
United States
 

Univ of Nebraska Med Ctr
Omaha,  Nebraska,  681985130
United States
 

Methodist Hosp of Indiana / Life Care Clinic
Indianapolis,  Indiana,  46202
United States
 

St Mary's Hosp (Univ of Rochester/Infectious Diseases)
Rochester,  New York,  14642
United States
 

Case Western Reserve Univ
Cleveland,  Ohio,  44106
United States
 

Community Health Network Inc
Rochester,  New York,  14642
United States
 


Additional Information:
Study ID Numbers:
  ACTG A5095;  Substudy AACTG 5097s,Substudy ACTG A5166s,AACTG 5095,Substudy AACTG 5107s,Substudy ACTG A5097s,Substudy AACTG 5166s,Substudy ACTG A5107s
Study Start Date: 
Record last reviewed: December 2003
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00013520

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