Clinical trial NCT00244712: Abacavir/Lamivudine Versus Emtricitabine/Tenofovir Both In Combination With Lopinavir/Ritonavir For The Treatment Of HIV
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infection
Keywords: HEAT
Antiretroviral-naive
HIV
EPZICOM
TRUVADA
KALETRA
once-daily
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-10-27
Enrollment: 688
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 by Missing=Failure (M=F), Switched Included Analysis.
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
timeFrame: Week 96
measure: 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
timeFrame: Weeks 48 and 96
measure: 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
timeFrame: Weeks 48 and 96
measure: Percentage of Participants With HIV-1 RNA <400 Copies/mL at Weeks 48 and 96
timeFrame: Weeks 48 and 96
measure: 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
timeFrame: Weeks 48 and 96
measure: 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
timeFrame: Weeks 48 and 96
measure: Median Change From Baseline in HIV-1 RNA at Week 48 and 96
timeFrame: Weeks 48 and 96
measure: Median Change From Baseline in CD4+ Cells at Weeks 48 and 96
timeFrame: Weeks 48 and 96
measure: Number of Participants Who Meet the Protocol-defined Virologic Failure (PDVF) Criteria at Week 96
timeFrame: Baseline to Week 96
measure: Number of Confirmed Virologic Failure Participants Who Had Treatment-emergent Genotypic Resistance Through 96 Weeks
timeFrame: Baseline and time of virologic failure (up to Week 96)
measure: Number of Confirmed Virologic Failure Participants at Week 96 With Genotypic Resistance to Lamivudine (3TC) and Emtricitabine (FTC) and Had Phenotypic Reduced Susceptibility
timeFrame: Baseline and time of virologic failure (up to Week 96)
measure: Number of Participants Who Reported a Suspected Abacavir Hypersensitivity Reaction (ABC HSR) Reaction or Proximal Renal Tubule Dysfunction
timeFrame: Baseline through 96 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Beverly Hills
country: United States
facility: GSK Investigational Site
state: California
city: Fountain Valley
country: United States
facility: GSK Investigational Site
state: California
city: Garden Grove
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Oakland
country: United States
facility: GSK Investigational Site
state: California
city: Oakland
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Glastonbury
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Norwalk
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Myers
country: United States
facility: GSK Investigational Site
state: Florida
city: Key West
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Plantation
country: United States
facility: GSK Investigational Site
state: Florida
city: Port St. Lucie
country: United States
facility: GSK Investigational Site
state: Florida
city: Sarasota
country: United States
facility: GSK Investigational Site
state: Florida
city: Sarasota
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Augusta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Decatur
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Maywood
country: United States
facility: GSK Investigational Site
state: Illinois
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Hillsborough
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Newark
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Somers Point
country: United States
facility: GSK Investigational Site
state: New Jersey
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Toledo
country: United States
facility: GSK Investigational Site
state: Ohio
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: West Reading
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Harlingen
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Longview
country: United States
facility: GSK Investigational Site
state: Texas
city: Tyler
country: United States
facility: GSK Investigational Site
state: Texas
city: Annandale
country: United States
facility: GSK Investigational Site
state: Virginia
city: Charlottesville
country: United States
facility: GSK Investigational Site
state: Virginia
city: Hampton
country: United States
facility: GSK Investigational Site
state: Virginia
city: Lynchburg
country: United States
facility: GSK Investigational Site
state: Virginia
city: Milwaukee
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Ponce
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.