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A Study to Evaluate Various Combinations of Anti-HIV Medications to Treat Early HIV Infection

Not Applicable
Completed
Conditions
HIV Infections
Registration Number
NCT00000919
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

The purpose of this study is to compare the effectiveness of various combinations of anti-HIV drugs in HIV-positive men and women. Patients receive specific combinations of 3 or 4 of the following 6 drugs: didanosine (ddI), stavudine (d4T) efavirenz (EFV), nelfinavir (NFV), lamivudine (3TC), or zidovudine (ZDV).

Anti-HIV therapy is effective in preventing the spread of HIV in the body. However, patients often experience unpleasant side effects and have difficulties following the dosing schedule. This study looks for combinations of anti-HIV drugs ("cocktails") which will be the most effective with the fewest problems.

Detailed Description

Highly active antiretroviral therapy, though effective in the suppression of HIV proliferation, is often complicated by difficulties with adherence and drug toxicity. Various combinations of highly active antiretroviral therapy exist; all have proved efficacious in related trials. The question addressed in this trial is which combination of antiretroviral "cocktails" provides the single greatest advantage in preventing the spread of HIV in the body. In effect, which therapy provides the greatest benefit with the fewest complications.

Step 1: Patients are randomized to 1 of 6 arms:

Arm A: didanosine (ddI), stavudine (d4T), efavirenz (EFV), and nelfinavir (NFV) placebo.

Arm B: ddI, d4T, EFV placebo, and NFV. Arm C: lamivudine (3TC)/zidovudine (ZDV), EFV, and NFV placebo. Arm D: 3TC/ZDV, EFV placebo, and NFV. Arm E: ddI, d4T, EFV, and NFV. Arm F: 3TC/ZDV, EFV, and NFV. Patients with virologic failure on 2 successive measurements or study-drug intolerance discontinue their randomized study therapy and proceed to Step 2. \[AS PER AMENDMENT 7/5/00: Patients must switch regimens as soon as possible after confirmation of virologic failure to prevent development of drug resistance.\]

Step 2:

Arm A: Patients receive treatment as in Arm D of Step 1. Arm B: Patients receive treatment as in Arm C of Step 1. Arm C: Patients receive treatment as in Arm B of Step 1. Arm D: Patients receive treatment as in Arm A of Step 1. Arms A, B, C, and D: Patients who fail Step 2 treatment proceed to Step 3. Arms E and F: Patients with virologic failure on Step 1 proceed immediately to Step 3.

Step 3 (salvage therapy):

Arm A, B, C, and D: Patients receive indinavir (IDV), amprenavir (APV), ddI, and hydroxyurea (HU).

\[AS PER AMENDMENT 7/5/00: Patients now receive treatment on Regimen 1, 2, 3, 4, 5, or 6. Regimen 1 consists of IDV, ritonavir (RTV), ddI, and HU. Regimen 2 consists of APV, RTV, ddI, and HU. Regimen 3 consists of IDV, RTV, abacavir (ABC), and 3TC/ZDV. Regimen 4 consists of APV, RTV, ABC, and 3TC/ZDV. Regimen 5 consists of IDV, RTV, ABC, d4T, and 3TC. Regimen 6 consists of APV, RTV, ABC, d4T, and 3TC.\] Arm E: Patients receive IDV, APV, and 3TC/ZDV. \[AS PER AMENDMENT 7/5/00: Patients now receive treatment on Regimen 7 or 8. Regimen 7 consists of IDV, RTV, and 3TC/ZDV. Regimen 8 consists of APV, RTV, and 3TC/ZDV.\] Arm F: Patients receive IDV, APV, ddI, and d4T. \[AS PER AMENDMENT 7/5/00: Patients now receive treatment on Regimen 9 or 10. Regimen 9 consists of IDV, RTV, ddI, and d4T. Regimen 10 consists of APV, RTV, ddI, and d4T.\] \[AS PER AMENDMENT 7/5/00: Patients already enrolled in Step 3 before site registration to Version 4.0 of this protocol have the option of receiving 1 of the appropriate new Step 3 regimens as outlined above or staying on their originally assigned Step 3 therapy.\] \[AS PER AMENDMENT 3/21/01: If virologic failure on Step 1 or 2 is confirmed, then HIV-1 RNA genotype resistance testing (in real-time, if possible) is performed. Patients receive 1 of the Step 3 drug regimens based on the results of the resistance testing.\] Patients may co-enroll in metabolic, pharmacologic, immunologic, or adherence substudies.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
900
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (80)

Univ of Southern California / LA County USC Med Ctr

🇺🇸

Los Angeles, California, United States

Marin County Specialty Clinic

🇺🇸

San Rafael, California, United States

Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr

🇺🇸

Atlanta, Georgia, United States

Cook County Hosp

🇺🇸

Chicago, Illinois, United States

Rush Presbyterian - Saint Luke's Med Ctr

🇺🇸

Chicago, Illinois, United States

Indiana Univ Hosp

🇺🇸

Indianapolis, Indiana, United States

Division of Inf Diseases/ Indiana Univ Hosp

🇺🇸

Indianapolis, Indiana, United States

Methodist Hosp of Indiana / Life Care Clinic

🇺🇸

Indianapolis, Indiana, United States

State of MD Div of Corrections / Johns Hopkins Univ Hosp

🇺🇸

Baltimore, Maryland, United States

Harvard (Massachusetts Gen Hosp)

🇺🇸

Boston, Massachusetts, United States

Boston Med Ctr

🇺🇸

Boston, Massachusetts, United States

Beth Israel Deaconess - West Campus

🇺🇸

Boston, Massachusetts, United States

Case Western Reserve Univ

🇺🇸

Cleveland, Ohio, United States

Univ of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Univ of Hawaii

🇺🇸

Honolulu, Hawaii, United States

Willow Clinic

🇺🇸

Menlo Park, California, United States

San Mateo AIDS Program / Stanford Univ

🇺🇸

Stanford, California, United States

Ohio State Univ Hosp Clinic

🇺🇸

Columbus, Ohio, United States

Univ of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

Univ of Kentucky Lexington

🇺🇸

Cincinnati, Ohio, United States

San Francisco AIDS Clinic / San Francisco Gen Hosp

🇺🇸

San Francisco, California, United States

Duke Univ Med Ctr

🇺🇸

Durham, North Carolina, United States

Carolinas Med Ctr

🇺🇸

Charlotte, North Carolina, United States

Univ of North Carolina

🇺🇸

Chapel Hill, North Carolina, United States

Archispedale S Maria Nuova

🇮🇹

Reggio Emilia, Italy

Akron City Hospital

🇺🇸

Akron, Ohio, United States

Univ of Pennsylvania at Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Univ of Rochester Medical Center

🇺🇸

Rochester, New York, United States

MetroHealth Med Ctr

🇺🇸

Cleveland, Ohio, United States

Philadelphia Veterans Administration Med Ctr

🇺🇸

Philadelphia, Pennsylvania, United States

Milton S Hershey Med Ctr

🇺🇸

Hershey, Pennsylvania, United States

Julio Arroyo

🇺🇸

West Columbia, South Carolina, United States

Univ of Puerto Rico

🇵🇷

San Juan, Puerto Rico

Azienda USL di Piacenza

Francesco Leoncini

Azienda Ospedaliera Umberto I

🇮🇹

Ancona, Italy

Ospedale S Orsola

🇮🇹

Bologna, Italy

Spedali Civili - Carosi

🇮🇹

Brescia, Italy

Spedali Civili Cadeo

🇮🇹

Brescia, Italy

Archispedale S Anna

🇮🇹

Ferrara, Italy

Universita di Genova

🇮🇹

Genova, Italy

Ospedale Luigi Cacco Moroni

🇮🇹

Milano, Italy

Ospedale Luigi Sacco Cargnel

🇮🇹

Milano, Italy

Azienda Ospedaliera di Parma

🇮🇹

Parma, Italy

IRCCS Policlinico S Matteo Filice

🇮🇹

Pavia, Italy

IRCCS Policlinico S Matteo Minoli

🇮🇹

Pavia, Italy

Ospedale Civile Maggiore

🇮🇹

Verona, Italy

Universita di Roma - Delia

🇮🇹

Roma, Italy

Univ of Pittsburgh Med Ctr

🇺🇸

Pittsburgh, Pennsylvania, United States

Univ of Washington

🇺🇸

Seattle, Washington, United States

Univ of Texas Galveston

🇺🇸

Galveston, Texas, United States

Moses H Cone Memorial Hosp

🇺🇸

Greensboro, North Carolina, United States

Univ of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

UCLA CARE Ctr

🇺🇸

Los Angeles, California, United States

Univ of California / San Diego Treatment Ctr

🇺🇸

San Diego, California, United States

San Francisco Gen Hosp

🇺🇸

San Francisco, California, United States

Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium

🇺🇸

San Jose, California, United States

Stanford Univ Med Ctr

🇺🇸

Stanford, California, United States

Harbor UCLA Med Ctr

🇺🇸

Torrance, California, United States

Georgetown Univ Hosp

🇺🇸

Washington, District of Columbia, United States

Univ of Colorado Health Sciences Ctr

🇺🇸

Denver, Colorado, United States

Univ of Miami School of Medicine

🇺🇸

Miami, Florida, United States

Howard Univ

🇺🇸

Washington, District of Columbia, United States

Emory Univ

🇺🇸

Atlanta, Georgia, United States

Northwestern Univ Med School

🇺🇸

Chicago, Illinois, United States

Univ of Iowa Hosp and Clinic

🇺🇸

Iowa City, Iowa, United States

Tulane Med Ctr Hosp

🇺🇸

New Orleans, Louisiana, United States

Charity Hosp / Tulane Univ Med School

🇺🇸

New Orleans, Louisiana, United States

Tulane Univ School of Medicine

🇺🇸

New Orleans, Louisiana, United States

Univ of Nebraska Med Ctr

🇺🇸

Omaha, Nebraska, United States

St Louis Regional Hosp / St Louis Regional Med Ctr

🇺🇸

St Louis, Missouri, United States

SUNY / Erie County Med Ctr at Buffalo

🇺🇸

Buffalo, New York, United States

Manhattan Veterans Administration / New York Univ Med Ctr

🇺🇸

New York, New York, United States

Mem Sloan - Kettering Cancer Ctr

🇺🇸

New York, New York, United States

Beth Israel Med Ctr

🇺🇸

New York, New York, United States

Cornell Univ Med Ctr

🇺🇸

New York, New York, United States

Mount Sinai Med Ctr

🇺🇸

New York, New York, United States

St Mary's Hosp (Univ of Rochester/Infectious Diseases)

🇺🇸

Rochester, New York, United States

Chelsea Ctr

🇺🇸

New York, New York, United States

Columbia Presbyterian Med Ctr

🇺🇸

New York, New York, United States

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