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Efavirenz or Atazanavir/Ritonavir Given With Emtricitabine/Tenofovir Disoproxil Fumarate or Abacavir/Lamivudine in HIV Infected Treatment-Naive Adults

Information source: AIDS Clinical Trials Group
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV Infections

Intervention: Abacavir/Lamivudine (Drug); Atazanavir (Drug); Efavirenz (Drug); Emtricitabine/Tenofovir disoproxil fumarate (Drug); Ritonavir (Drug); Abacavir/Lamivudine placebo (Drug); Emtricitabine/Tenofovir disoproxil fumarate placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: AIDS Clinical Trials Group

Official(s) and/or principal investigator(s):
Eric Daar, MD, Study Chair, Affiliation: Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute
Paul Sax, MD, Study Chair, Affiliation: Division of Infectious Diseases, Brigham and Women's Hospital

Summary

Currently, the preferred anti-HIV regimens used in the United States consist of two nucleoside reverse transcriptase inhibitors (NRTIs) and the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV). However, with new anti-HIV drugs being approved, alternative regimens need to be tested to determine if new drug combinations have increased effectiveness in treating HIV. The purpose of this study is to test the safety, tolerability, and effectiveness of four different regimens in HIV-infected adults who have never taken anti-HIV drugs.

Clinical Details

Official title: A Phase IIIB, Randomized Trial of Open-Label Efavirenz or Atazanavir With Ritonavir in Combination With Double-Blind Comparison of Emtricitabine/Tenofovir or Abacavir/Lamivudine in Antiretroviral-Naive Subjects

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Time From Randomization to Virologic Failure

Time From Treatment Dispensation to a Grade 3/4 Safety Event

Time From Treatment Dispensation to Treatment Modification

Secondary outcome:

Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification)

The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL

Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL

Change in CD4 Count (Cells/mm3) From Baseline

Number of Participants With Virologic Failure and Emergence of Major Resistance

Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events.

Change in Fasting Total Cholesterol Level From Baseline

Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline

Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline

Change in Fasting Triglyceride Level From Baseline

Detailed description: Antiretroviral (ARV) treatment regimens consisting of EFV and two NRTIs are the most commonly prescribed regimens for the initial therapy of HIV-infected people in the United States. Such regimens are popular because the drugs are easy to administer, have overall excellent efficacy, and are well tolerated. However, because of concerns about long-term drug toxicity, the development of drug resistance, and potential complications in pregnant women, it is imperative that other drug combinations be investigated as possible alternative initial regimens. Drugs recently approved by the Food and Drug Administration (FDA) for HIV treatment include the protease inhibitor (PI) atazanavir (ATV) and the two NRTI coformulations emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and abacavir/lamivudine (ABC/3TC). Data are limited on the efficacy of these new drugs when part of anti-HIV drug regimens. This study will evaluate and compare the safety, tolerability, and efficacy of four different treatment regimens in HIV-infected treatment-naive adults. The treatment portion of this study will last 96 weeks after the last participant is enrolled. Participants will be randomly assigned to one of four arms:

- Arm 1 participants will receive EFV, FTC/TDF, and placebo for ABC/3TC.

- Arm 2 participants will receive EFV, ABC/3TC, and placebo for FTC/TDF.

- Arm 3 participants will receive ritonavir (RTV)-boosted ATV, FTC/TDF, and placebo for

ABC/3TC.

- Arm 4 participants will receive RTV-boosted ATV, ABC/3TC and placebo for FTC/TDF.

NOTE: Lopinavir/ritonavir may be used in substitution of other drugs for certain participants. Study visits will occur at study entry; Weeks 1, 2, 4, 8, 16, and 24; and every 12 weeks thereafter. A physical exam, blood collection, and urine collection will occur at most visits. Two pharmacokinetic blood samples will be collected from participants between Weeks 4 and 24. Participants will undergo adherence training at study entry and will be asked to complete adherence questionnaires at selected study visits. Some participants will be asked to participate in ACTG A5224s, a metabolic substudy of ACTG A5202. The Data Safety Monitoring Board (DSMB) for A5202 met in January 2008 to review the study. After reviewing the study information, the DSMB noted that certain study regimens were significantly less effective than others. Specifically, ABC/3TC-containing regimens were not as effective in controlling the virus as TDF/FTC-containing regimens for participants entering the study with high viral loads. The DSMB also commented that participants assigned to ABC/3TC had a shorter time until they experienced side effects than participants assigned to TDF/FTC. The DSMB had no safety concerns for the other drug comparisons. Based on DSMB review, in Feb 2008 participants who started the study with high viral loads were told whether they were taking ABC/3TC or TDF/FTC and offered the option to continue or change their NRTI study drug component, after discussion with their doctor. For participants who started the study with lower screening viral loads, study treatment continued without change. For 74 participant the reason for first treatment modification was "unblinded and switched" as a consequence of the DSMB results (33 on EFV, ABC/3TC, and placebo FTC/TDF arm; 1 on RTV-boosted ATV, FTC/TDF, and placebo ABC/3TC arm; and 40 on RTV-boosted ATV, ABC/3TC, and placebo FTC/TDF arm).

Eligibility

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- HIV-infected. A resistance assay must be obtained if the participant has evidence of

recent infection. More information on this criterion can be found in the protocol.

- Antiretroviral naive, defined as 7 days or less of ARV treatment at any time prior to

study entry. Participants who have received ARVs as part of postexposure prophylaxis or who have received an investigational drug that was not an NRTI, NNRTI, or PI are eligible for this study.

- HIV viral load greater than 1,000 copies/ml within 90 days prior to study entry

- Certain laboratory values obtained within 30 days prior to study entry. More

information on this criterion can be found in the protocol

- Willing to use acceptable forms of contraception

- Parent or guardian able and willing to provide written informed consent, if

applicable

- Hepatitis B surface antigen (HBsAg) negative at study entry

Exclusion Criteria:

- Immunomodulators (e. g., interleukins, interferons, cyclosporine), HIV vaccine,

systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. Individuals receiving either stable physiologic glucocorticoid doses, corticosteroids for acute therapy for pneumocystis pneumonia, or a short course (2 weeks or less) of pharmacologic glucocorticoid therapy will not be excluded.

- Known allergy/sensitivity to study drugs or their formulations

- Active alcohol or drug use that, in the opinion of the investigator, would interfere

with adherence to study requirements

- Serious illness requiring systemic treatment or hospitalization. Patients who have

completed therapy or are clinically stable on therapy for at least 7 days prior to study entry are not excluded.

- Known clinically relevant cardiac conduction system disease

- Requirement for any current medications that are prohibited with any study treatment.

- Evidence of any major drug resistance-associated mutation on any genotype or evidence

of significant resistance on any phenotype performed at any time prior to study entry.

- Current imprisonment or involuntary incarceration for psychiatric or physical (e. g.,

infectious disease) illness

- Breastfeeding. Women who become pregnant during the study will be unblinded and

required to permanently discontinue their study regimens.

Locations and Contacts

Puerto Rico-AIDS CRS (5401), San Juan 00935, Puerto Rico

UCLA CARE Center CRS (601), Los Angeles, California 90035, United States

Usc Crs (1201), Los Angeles, California 90033, United States

Stanford CRS (501), Palo Alto, California 94304, United States

Ucsd, Avrc Crs (701), San Diego, California 92103, United States

Ucsf Aids Crs (801), San Francisco, California 94110, United States

San Mateo County AIDS Program (505), Stanford, California 94305-5107, United States

Willow Clinic (507), Stanford, California 94305-5107, United States

Harbor-UCLA Med. Ctr. CRS (603), Torrance, California 90502, United States

University of Colorado Hospital CRS (6101), Aurora, Colorado 80045, United States

Georgetown University CRS (GU CRS) (1008), Washington, District of Columbia 20007, United States

University of Miami AIDS CRS (901), Miami, Florida 33139, United States

Emory University, Atlanta, Georgia 30308, United States

The Ponce de Leon Center CRS (5802), Atlanta, Georgia 30308, United States

Cook County Hospital Core Center (2705), Chicago, Illinois 60612, United States

Northwestern University CRS (2701), Chicago, Illinois 60611, United States

Rush Univ. Med. Ctr. ACTG CRS (2702), Chicago, Illinois 60612, United States

Indiana University Hospital (2601), Indianapolis, Indiana 46202-5250, United States

Wishard Hospital (2603), Indianapolis, Indiana 46202, United States

Univ of Iowa Hosp and Clinic (1504), Iowa City, Iowa 52242, United States

IHV Baltimore Treatment CRS (4651), Baltimore, Maryland 21201, United States

Johns Hopkins Adult AIDS CRS (201), Baltimore, Maryland 21287, United States

Beth Israel Deaconess Med. Ctr., ACTG CRS (103), Boston, Massachusetts 02215, United States

Bmc Actg Crs (104), Boston, Massachusetts 02118, United States

Brigham and Women's Hosp. ACTG CRS (107), Boston, Massachusetts 02115, United States

Massachusetts General Hospital ACTG CRS (101), Boston, Massachusetts 02114, United States

Washington U CRS (2101), St. Louis, Missouri 63110, United States

SUNY - Buffalo (Rochester) (1102), Buffalo, New York 14215, United States

Cornell CRS (7804), New York, New York 10011, United States

Harlem ACTG CRS (31483), New York, New York 10037, United States

HIV Prevention & Treatment CRS (30329), New York, New York 10032, United States

NY Univ. HIV/AIDS CRS (401), New York, New York 10016, United States

Weill Med. College of Cornell Univ., The Cornell CTU -Chelsea (7803), New York, New York 10011, United States

AIDS Community Health Ctr. ACTG CRS (1108), Rochester, New York 14604, United States

University of Rochester ACTG CRS (1101), Rochester, New York 14642, United States

Unc Aids Crs (3201), Chapel Hill, North Carolina 27514, United States

Wake County Department of Health (30076), Chapel HIll, North Carolina 27514, United States

Duke University Medical Center Adult CRS (1601), Durham, North Carolina 27710, United States

Moses H. Cone Memorial Hospital CRS (3203), Greensboro, North Carolina 27401, United States

University of Cincinnati CRS (2401), Cincinnati, Ohio 45267, United States

Case CRS (2501), Cleveland, Ohio 44106, United States

Metro Health CRS (2503), Cleveland, Ohio 44109, United States

The Ohio State Univ. AIDS CRS (2301), Columbus, Ohio 43210, United States

Presbyterian Medical Center - Univ. of PA (6206), Norristown, Pennsylvania 19401, United States

Hosp. of the Univ. of Pennsylvania CRS (6201), Philadelphia, Pennsylvania 19104, United States

Pitt CRS (1001), Pittsburgh, Pennsylvania 15213, United States

The Miriam Hosp. ACTG CRS (2951), Providence, Rhode Island 02906, United States

Vanderbilt Therapeutics CRS (3652), Nashville, Tennessee 37232, United States

Peabody Health Center CRS (31443), Dallas, Texas 75215, United States

University of Texas, Galveston (6301), Galveston, Texas 77555-0435, United States

University of Washington AIDS CRS (1401), Seattle, Washington 98104, United States

University of Washington General Clinical Research (1403), Seattle, Washington 98104, United States

Additional Information

Click here for more information on abacavir/lamivudine

Click here for more information on atazanavir

Click here for more information on efavirenz

Click here for more information on emtricitabine/tenofovir disoproxil fumarate

Click here for more information on lopinavir/ritonavir

Click here for more information on ritonavir

Click here for more information on starting anti-HIV medications

Haga clic aquí para ver información sobre este ensayo clínico en español.

Related publications:

Anderson PL. Pharmacologic perspectives for once-daily antiretroviral therapy. Ann Pharmacother. 2004 Nov;38(11):1924-34. Epub 2004 Oct 12. Review.

Kress KD. HIV update: emerging clinical evidence and a review of recommendations for the use of highly active antiretroviral therapy. Am J Health Syst Pharm. 2004 Oct 1;61 Suppl 3:S3-14; quiz S15-6. Review. Erratum in: Am J Health Syst Pharm. 2004 Nov 15;61(22):2350.

Robbins GK, De Gruttola V, Shafer RW, Smeaton LM, Snyder SW, Pettinelli C, Dubé MP, Fischl MA, Pollard RB, Delapenha R, Gedeon L, van der Horst C, Murphy RL, Becker MI, D'Aquila RT, Vella S, Merigan TC, Hirsch MS; AIDS Clinical Trials Group 384 Team. Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med. 2003 Dec 11;349(24):2293-303.

Shafer RW, Smeaton LM, Robbins GK, De Gruttola V, Snyder SW, D'Aquila RT, Johnson VA, Morse GD, Nokta MA, Martinez AI, Gripshover BM, Kaul P, Haubrich R, Swingle M, McCarty SD, Vella S, Hirsch MS, Merigan TC; AIDS Clinical Trials Group 384 Team. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med. 2003 Dec 11;349(24):2304-15.

Starting date: September 2005
Last updated: February 15, 2011

Page last updated: August 20, 2015

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