Abacavir/Lamivudine Versus Emtricitabine/Tenofovir Both In Combination With Lopinavir/Ritonavir For The Treatment Of HIV (HEAT)

Study Description

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Brief Summary:

This study was designed to test the safety and effectiveness of EPZICOM(abacavir/lamivudine) and TRUVADA (emtricitabine/tenofovir) for the treatment of HIV infection when both are used in combination with KALETRA (lopinavir/ritonavir) over 96 weeks

Condition or disease	Intervention/treatment	Phase
HIV Infection	Drug: emtricitabine/tenofovir; Drug: abacavir/lamivudine	Phase 4

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	688 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A 96-Week, Phase IV, Randomized, Double-Blind, Multicenter Study of the Safety and Efficacy of EPZICOM Versus TRUVADA Administered in Combination With KALETRA in Antiretroviral-Naive HIV-1 Infected Subjects
Study Start Date :	July 2005
Actual Primary Completion Date :	April 2008
Actual Study Completion Date :	April 2008

Arms and Interventions

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Arm	Intervention/treatment
Experimental: ABC/3TC; The intervention is a regimen containing abacavir/lamivudine + tenofovir/emtricitabine placebo +lopinavir/ritonavir.	Drug: abacavir/lamivudine; The experimental intervention is a regimen containing abacavir/lamivudine + tenofovir/emtricitabine placebo + lopinavir/ritonavir.
Active Comparator: TDF/FTC; The intervention is a regimen containing tenofovir/emtricitabine + abacavir/lamivudine placebo + lopinavir/ritonavir.	Drug: emtricitabine/tenofovir; The intervention is an active comparator regimen containing tenofovir/emtricitabine + abacavir/lamivudine placebo + lopinavir/ritonavir.

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 by Missing=Failure (M=F), Switched Included Analysis. [ Time Frame: Week 48 ]
   A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Week 48. The percentage of participants with HIV-1 RNA <50 copies/mL were tabulated by treatment arm with stratification by baseline HIV-1 RNA (<100,000 copies/mL and >=100,000 copies/mL).

Secondary Outcome Measures :

1. Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 [ Time Frame: Week 48 ]
   A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Week 48. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 were tabulated by treatment arm with stratification by baseline HIV-1 RNA levels (<100,000 copies/mL and >=100,000 copies/mL).
2. Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 [ Time Frame: Week 96 ]
   A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Week 96. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 were tabulated by treatment arm with stratification by baseline HIV-1 RNA levels (<100,000 copies/mL and >=100,000 copies/mL).
3. Percentage of Participants With HIV-1 RNA <50 Copies/mL at Weeks 48 and 96 in Participants With Baseline HIV-1 RNA <100,000 Copies/mL [ Time Frame: Weeks 48 and 96 ]
   A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Weeks 48 and 96. The percentage of participants with HIV-1 RNA <50 copies/mL at Weeks 48 and 96 were tabulated by treatment arm in participants with baseline HIV-1 RNA <100,000 copies/mL.
4. Percentage of Participants With HIV-1 RNA <50 Copies/mL at Weeks 48 and 96 in Participants With Baseline HIV-1 RNA >=100,000 Copies/mL [ Time Frame: Weeks 48 and 96 ]
   A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Week 48 and 96. The percentage of participants with HIV-1 RNA <50 copies/mL at Weeks 48 and 96 were tabulated by treatment arm in participants with baseline HIV-1 RNA >=100,000 copies/mL.
5. Percentage of Participants With HIV-1 RNA <400 Copies/mL at Weeks 48 and 96 [ Time Frame: Weeks 48 and 96 ]
   A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Week 48 and 96. The percentage of participants with HIV-1 RNA <400 copies/mL at Weeks 48 and 96 were tabulated by treatment arm with stratification by baseline HIV-1 RNA levels (<100,000 copies/mL and >=100,000 copies/mL).
6. Percentage of Participants With HIV-1 RNA <400 Copies/mL at Weeks 48 and 96 in Participants With Baseline HIV-1 RNA <100,000 Copies/mL [ Time Frame: Weeks 48 and 96 ]
   A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Weeks 48 and 96. The percentage of participants with HIV-1 RNA <400 copies/mL at Weeks 48 and 96 were tabulated by treatment arm in participants with baseline HIV-1 RNA <100,000 copies/mL.
7. Percentage of Participants With HIV-1 RNA <400 Copies/mL at Weeks 48 and 96 in Participants With Baseline HIV-1 RNA >=100,000 Copies/mL [ Time Frame: Weeks 48 and 96 ]
   A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Weeks 48 and 96. The percentage of participants with HIV-1 RNA <400 copies/mL at Weeks 48 and 96 were tabulated by treatment arm in participants with baseline HIV-1 RNA >=100,000 copies/mL.
8. Median Change From Baseline in HIV-1 RNA at Week 48 and 96 [ Time Frame: Weeks 48 and 96 ]
   A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at Weeks 48 and 96. Change from baseline was defined as HIV-1 RNA level at Weeks 48 and 96 minus HIV-1 RNA level at baseline.
9. Median Change From Baseline in CD4+ Cells at Weeks 48 and 96 [ Time Frame: Weeks 48 and 96 ]
   A blood sample was drawn to determine the CD4+ cell count at Weeks 48 and 96. Change from baseline was defined as CD4+ cell count at week 96 minus CD4+ cell count at baseline.
10. Number of Participants Who Meet the Protocol-defined Virologic Failure (PDVF) Criteria at Week 96 [ Time Frame: Baseline to Week 96 ]
    The number of participants that failed to respond to therapy based on the protocol definition of virologic failure (PDVF) was tabulated. PDVF was defined as either no confirmed HIV-1 RNA <200 copies/mL or HIV-1 RNA rebound >= 200 copies/mL on two consecutive occasions.
11. Number of Confirmed Virologic Failure Participants Who Had Treatment-emergent Genotypic Resistance Through 96 Weeks [ Time Frame: Baseline and time of virologic failure (up to Week 96) ]
    A blood sample was drawn for participants failing to respond to therapy and the mutations present in the virus were identified. For each participant, the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New mutations that developed at the time of failure was tabulated by drug class. NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
12. Number of Confirmed Virologic Failure Participants at Week 96 With Genotypic Resistance to Lamivudine (3TC) and Emtricitabine (FTC) and Had Phenotypic Reduced Susceptibility [ Time Frame: Baseline and time of virologic failure (up to Week 96) ]
    A blood sample was drawn for participants failing to respond to therapy and the mutations present in the virus were identified. New mutations that developed to the NRTI class at the time of failure that no longer responded to lamivudine or emtricitabine were tabulated by drug class.
13. Number of Participants Who Reported a Suspected Abacavir Hypersensitivity Reaction (ABC HSR) Reaction or Proximal Renal Tubule Dysfunction [ Time Frame: Baseline through 96 weeks ]
    The number of participants that experienced symptoms of a suspected abacavir hypersensitivity reaction was tabulated. The number of participants that developed laboratory signs of proximal renal tubule dysfunction was tabulated.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

• Males as females at least 18 years old. (A female is eligible to enter and participate in this study if she is of: non child-bearing potential, child bearing potential with a negative pregnancy test and agrees to approved contraception methods, or agreement for complete abstinence.)
• Subject is antiretroviral-naïve (defined as having ≤14 days of prior therapy with any NRTI and no prior therapy with either a PI or NNRTI).
• Subject has plasma HIV-1 RNA ≥ 1,000 copies/mL at screening.
• Subject is willing and able to understand and provide written informed consent prior to participation in this study.

Exclusion criteria:

• Subject has an active or acute CDC Clinical Category C event (exclusive of cutaneous Kaposi's sarcoma) at screening. Treatment for the acute event must have been completed at least 30 days prior to screening.
• Subject is enrolled in one or more investigational drug protocols, which may impact HIV-1 RNA suppression.
• Subject is, in the opinion of the investigator, unable to complete the 96-week dosing period and protocol evaluations and assessments.
• Subject is either pregnant or breastfeeding.
• Subject has an ongoing clinically relevant pancreatitis or clinically relevant hepatitis at screening.
• Subject suffers from a serious medical condition, such as cirrhosis, diabetes, congestive heart failure, cardiomyopathy or other cardiac dysfunction, which in the opinion of the investigator would compromise the safety of the subject.
• Subject has a pre-existing mental, physical, or substance abuse disorder which, in the opinion of the investigator, may interfere with the subject's ability to comply with the dosing schedule and protocol evaluations and assessments.
• Subject has a history of inflammatory bowel disease or malignancy, intestinal ischemia, malabsorption, or other gastrointestinal dysfunction which may interfere with drug absorption or render the subject unable to take oral medication.
• Subject has any acute laboratory abnormality at screening, which, in the opinion of the investigator, precludes the subject's participation in the study of an investigational compound. Any grade 4 laboratory abnormality will exclude a subject from study participation.
• Subject has estimated creatinine clearance <50 mL/min via Cockroft-Gault method.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN).
• Subject has required treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to screening, or has an anticipated need for these agents within the study period.
• Subject requires treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, vaccines, or interferons) within 28 days prior to Screen, or subject has received an HIV-1 immunotherapeutic vaccine within 90 days prior to Screen. Asthmatic subjects using inhaled corticosteroids are eligible for enrollment.
• Subject requires treatment with foscarnet, hydroxyurea or other agents with documented activity against HIV-1 in vitro within 28 days of study administration.
• Subjects who require treatment with the prohibited medications within 28 days of commencement of investigational product, or an anticipated need during the study.
• Subject has a history of allergy to any of the study drugs or any excipients therein

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:	GSK Clinical Trials	GlaxoSmithKline

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Smith KY, Patel P, Fine D, Bellos N, Sloan L, Lackey P, Kumar PN, Sutherland-Phillips DH, Vavro C, Yau L, Wannamaker P, Shaefer MS; HEAT Study Team. Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment. AIDS. 2009 Jul 31;23(12):1547-56. doi: 10.1097/QAD.0b013e32832cbcc2.

Responsible Party:	Study Director, GSK
ClinicalTrials.gov Identifier:	NCT00244712 History of Changes
Other Study ID Numbers:	EPZ104057; EPZ104057
First Posted:	October 27, 2005
Results First Posted:	September 15, 2009
Last Update Posted:	June 8, 2010
Last Verified:	June 2010

Keywords provided by GlaxoSmithKline:

HEAT; Antiretroviral-naive; HIV; EPZICOM	TRUVADA; KALETRA; once-daily

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Ritonavir; Lopinavir; Tenofovir; Lamivudine; Emtricitabine; Abacavir

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Dideoxynucleosides; HIV Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Antimetabolites