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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: emtricitabine/tenofovir
* Drug: abacavir/lamivudine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABC/3TC<br>The intervention is a regimen containing abacavir/lamivudine + tenofovir/emtricitabine placebo +lopinavir/ritonavir. | Drug: abacavir/lamivudine<br>* The experimental intervention is a regimen containing abacavir/lamivudine + tenofovir/emtricitabine placebo + lopinavir/ritonavir.<br>|
| Active Comparator: TDF/FTC<br>The intervention is a regimen containing tenofovir/emtricitabine + abacavir/lamivudine placebo + lopinavir/ritonavir. | Drug: emtricitabine/tenofovir<br>* The intervention is an active comparator regimen containing tenofovir/emtricitabine + abacavir/lamivudine placebo + lopinavir/ritonavir.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 by Missing=Failure (M=F), Switched Included Analysis. | 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). | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at 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). | Week 48 | 
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at 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). | Week 96 | 
| 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 | 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. | Weeks 48 and 96 | 
| 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 | 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. | Weeks 48 and 96 | 
| Percentage of Participants With HIV-1 RNA <400 Copies/mL at 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). | Weeks 48 and 96 | 
| 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 | 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. | Weeks 48 and 96 | 
| 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 | 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. | Weeks 48 and 96 | 
| Median Change From Baseline in HIV-1 RNA at Week 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. | Weeks 48 and 96 | 
| Median Change From Baseline in CD4+ Cells at 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. | Weeks 48 and 96 | 
| Number of Participants Who Meet the Protocol-defined Virologic Failure (PDVF) Criteria at 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. | Baseline to Week 96 | 
| Number of Confirmed Virologic Failure Participants Who Had Treatment-emergent Genotypic Resistance Through 96 Weeks | 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. | Baseline and time of virologic failure (up to Week 96) | 
| Number of Confirmed Virologic Failure Participants at Week 96 With Genotypic Resistance to Lamivudine (3TC) and Emtricitabine (FTC) and Had Phenotypic Reduced Susceptibility | 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. | Baseline and time of virologic failure (up to Week 96) | 
| Number of Participants Who Reported a Suspected Abacavir Hypersensitivity Reaction (ABC HSR) Reaction or Proximal Renal Tubule Dysfunction | 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. | Baseline through 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HEAT, Antiretroviral-naive, HIV, EPZICOM, TRUVADA, KALETRA, once-daily