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

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00118898

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Drug: Abacavir/Lamivudine Drug: Atazanavir Drug: Efavirenz Drug: Emtricitabine/Tenofovir disoproxil fumarate Drug: Ritonavir Drug: Abacavir/Lamivudine placebo Drug: Emtricitabine/Tenofovir disoproxil fumarate placebo	Phase III

MedlinePlus related topics: AIDS

Drug Information available for: Abacavir Abacavir sulfate Lamivudine Efavirenz Ritonavir Atazanavir sulfate BMS 232632 Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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

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

Primary Outcome Measures:

Time from randomization to virologic failure [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Time from treatment dispensation to the first development of a Grade 3 or 4 sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Time from treatment dispensation to treatment discontinuation [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time from treatment dispensation to regimen completion (first occurrence of virologic failure or treatment discontinuation) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
HIV viral load levels less than 50 and less than 200 copies/ml [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
CD4 count and other immunologic responses [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
HIV-1 drug resistance patterns [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Occurrence of fasting hypertriglyceridemia, indication of drug therapy of dyslipidemia, receipt of new drug therapy for dyslipidemia, change from baseline in components of lipid panel [ Time Frame: At Weeks 8, 24, 48, 72, and 96 ] [ Designated as safety issue: No ]
Virologic and immunologic response, safety, and tolerability by race/ethnicity, age, gender, and hepatitis B and C coinfection [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Occurrence of targeted clinical events, including death, AIDS-defining illness, and HIV-1 related events (including the CDC Category B diseases) [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Enrollment:	1864
Study Start Date:	September 2005
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants will receive EFV, FTC/TDF, and placebo for ABC/3TC for 96 weeks	Drug: Efavirenz 600 mg tablet taken orally daily Drug: Emtricitabine/Tenofovir disoproxil fumarate 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate tablet taken orally daily Drug: Abacavir/Lamivudine placebo Placebo tablet taken orally daily
2: Experimental Participants will receive EFV, placebo for FTC/TDF, and ABC/3TC for 96 weeks	Drug: Abacavir/Lamivudine 600 mg abacavir/300 mg lamivudine tablet taken orally daily Drug: Efavirenz 600 mg tablet taken orally daily Drug: Emtricitabine/Tenofovir disoproxil fumarate placebo Placebo tablet taken orally daily
3: Experimental Participants will receive RTV-boosted ATV, FTC/TDF, and placebo for ABC/3TC for 96 weeks	Drug: Atazanavir 300 mg tablet taken orally daily Drug: Emtricitabine/Tenofovir disoproxil fumarate 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate tablet taken orally daily Drug: Ritonavir 100 mg tablet taken orally daily Drug: Abacavir/Lamivudine placebo Placebo tablet taken orally daily
4: Experimental Participants will receive RTV-boosted ATV, placebo for FTC/TDF, and ABC/3TC for 96 weeks	Drug: Abacavir/Lamivudine 600 mg abacavir/300 mg lamivudine tablet taken orally daily Drug: Atazanavir 300 mg tablet taken orally daily Drug: Ritonavir 100 mg tablet taken orally daily Drug: Emtricitabine/Tenofovir disoproxil fumarate placebo Placebo tablet taken orally daily

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. Participants will be followed for an additional 48 weeks after the treatment portion is completed. 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, placebo for FTC/TDF, and ABC/3TC.
Arm 3 participants will receive ritonavir (RTV)-boosted ATV, FTC/TDF, and placebo for ABC/3TC.
Arm 4 participants will receive RTV-boosted ATV, placebo for FTC/TDF, and ABC/3TC.

NOTE: Lopinavir/ritonavir may be used in substitution of other drugs for certain participants.

There will be 16 study visits that 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.

Eligibility

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

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 of study entry
Willing to use acceptable forms of contraception
Parent or guardian willing to provide 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, may interfere with the study
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
Require certain medications
Any major drug resistance-associated mutation on genotypic resistance testing or evidence of significant resistance on any phenotype
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00118898

Show 64 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Eric Daar, MD	Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute
Study Chair:	Paul Sax, MD	Division of Infectious Diseases, Brigham and Women's Hospital

More Information

Click here for more information on abacavir/lamivudine This link exits the ClinicalTrials.gov site

Click here for more information on atazanavir This link exits the ClinicalTrials.gov site

Click here for more information on efavirenz This link exits the ClinicalTrials.gov site

Click here for more information on emtricitabine/tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Click here for more information on lopinavir/ritonavir This link exits the ClinicalTrials.gov site

Click here for more information on ritonavir This link exits the ClinicalTrials.gov site

Click here for more information on starting anti-HIV medications This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

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, Dube 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.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5202, ACTG 5224s
Study First Received:	July 7, 2005
Last Updated:	September 26, 2008
ClinicalTrials.gov Identifier:	NCT00118898
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Treatment Naive

Study placed in the following topic categories:

Efavirenz
Sexually Transmitted Diseases, Viral
Acquired Immunodeficiency Syndrome
Lamivudine
Atazanavir
Immunologic Deficiency Syndromes
Virus Diseases
Emtricitabine

HIV Infections
Ritonavir
Sexually Transmitted Diseases
Tenofovir
Abacavir
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
HIV Protease Inhibitors
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection

Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009