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

Sponsor:	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

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

Resource links provided by NLM:

MedlinePlus related topics: AIDS

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

U.S. FDA Resources

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

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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.

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

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5202, ACTG 5224s
Study First Received:	July 7, 2005
Last Updated:	June 30, 2009
ClinicalTrials.gov Identifier:	NCT00118898 History of Changes
Health Authority:	United States: Federal Government