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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00244712
First received: October 25, 2005
Last updated: June 3, 2010
Last verified: June 2010
Results First Received: April 23, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: HIV Infection
Interventions: Drug: emtricitabine/tenofovir
Drug: abacavir/lamivudine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited at 76 study sites in the US and 2 study sites in Puerto Rico between 26 July 2005 and 16 June 2006.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
After screening, participants who had never received treatment for HIV-1 infection and had a viral load greater than or equal to 1,000 copies per milliliter of blood and any amount of CD4+ T-cells were equally randomized to 1 of 2 treatment groups.

Reporting Groups
  Description
Abacavir/Lamivudine (ABC/3TC) + Lopinavir/Ritonavir (LPV/RTV) 1 tablet (600mg/300mg) ABC/3TC + 800mg/200mg LPV/RTV combination therapy once daily
Tenofovir/Emtricitabine (TDF/FTC) + LPV/RTV 1 tablet (300mg/200mg) TDF/FTC + 800mg/200mg LPV/RTV combination therapy once daily

Participant Flow:   Overall Study
    Abacavir/Lamivudine (ABC/3TC) + Lopinavir/Ritonavir (LPV/RTV)     Tenofovir/Emtricitabine (TDF/FTC) + LPV/RTV  
STARTED     343     345  
COMPLETED     234     221  
NOT COMPLETED     109     124  
Adverse Event                 20                 21  
Protocol-Defined Virologic Failure                 8                 6  
Lack of Compliance                 10                 11  
Lost to Follow-up                 45                 52  
Withdrawal by Subject                 13                 23  
Protocol Violation, disease progression                 13                 11  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Abacavir/Lamivudine (ABC/3TC) + Lopinavir/Ritonavir (LPV/RTV) 1 tablet (600mg/300mg) ABC/3TC + 800mg/200mg LPV/RTV combination therapy once daily
Tenofovir/Emtricitabine (TDF/FTC) + LPV/RTV 1 tablet (300mg/200mg) TDF/FTC + 800mg/200mg LPV/RTV combination therapy once daily
Total Total of all reporting groups

Baseline Measures
    Abacavir/Lamivudine (ABC/3TC) + Lopinavir/Ritonavir (LPV/RTV)     Tenofovir/Emtricitabine (TDF/FTC) + LPV/RTV     Total  
Number of Participants  
[units: participants]
  343     345     688  
Age  
[units: years]
Mean ± Standard Deviation
  38.0  ± 9.80     38.7  ± 9.55     38.3  ± 9.68  
Gender  
[units: participants]
     
Female     56     69     125  
Male     287     276     563  
Race/Ethnicity, Customized  
[units: participants]
     
African American/African Heritage     122     124     246  
American Indian or Alaskan Native     0     1     1  
Asian     6     9     15  
White     177     174     351  
Mixed Race     2     1     3  
Unspecified     36     36     72  
Race/Ethnicity, Customized  
[units: participants]
     
Hispanic or Latino     73     62     135  
Not Hispanic or Latino     270     282     552  
Missing Information     0     1     1  
Baseline CD4+ Cell Count Level  
[units: participants]
     
<50 cells per cmm     61     70     131  
50 - <200 cells per cmm     99     110     209  
>= 200 cells per cmm     183     165     348  
Baseline HIV-1 RNA Level  
[units: participants]
     
<100,000 copies/mL     188     205     393  
100,000 - <250,000 copies/mL     68     75     143  
250,000 - <500,000 copies/mL     37     33     70  
>=500,000 copies/mL     50     32     82  
Centers for Disease Control (CDC) Classification [1]
[units: participants]
     
A: Asymptomatic HIV infection     229     240     469  
B: Symptomatic HIV infection     59     48     107  
C: AIDS     55     57     112  
Hepatitis B Infection  
[units: participants]
     
Reactive     19     9     28  
Non-Reactive     324     334     658  
Missing     0     2     2  
Hepatitis C Infection  
[units: participants]
     
Reactive     27     24     51  
Non-Reactive     316     319     635  
Missing     0     2     2  
Baseline CD4+ Cell Count  
[units: cells per cmm]
Median ( Full Range )
  214  
  ( 19 to 962 )  
  193  
  ( 19 to 953 )  
  202  
  ( 19 to 962 )  
Baseline HIV-1 RNA [2]
[units: log10 copies/mL]
Median ( Full Range )
  4.903  
  ( 2.658 to 6.994 )  
  4.844  
  ( 1.690 to 6.565 )  
  4.876  
  ( 1.690 to 6.994 )  
[1] HIV, Human Immunodeficiency Virus; AIDS, Acquired Immunodeficiency Syndrome
[2] HIV-1 RNA, Human Immunodeficiency Virus type 1 Ribonucleic acid



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Secondary:   Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48   [ Time Frame: Week 48 ]

3.  Secondary:   Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96   [ Time Frame: Week 96 ]

4.  Secondary:   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 ]

5.  Secondary:   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 ]

6.  Secondary:   Percentage of Participants With HIV-1 RNA <400 Copies/mL at Weeks 48 and 96   [ Time Frame: Weeks 48 and 96 ]

7.  Secondary:   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 ]

8.  Secondary:   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 ]

9.  Secondary:   Median Change From Baseline in HIV-1 RNA at Week 48 and 96   [ Time Frame: Weeks 48 and 96 ]

10.  Secondary:   Median Change From Baseline in CD4+ Cells at Weeks 48 and 96   [ Time Frame: Weeks 48 and 96 ]

11.  Secondary:   Number of Participants Who Meet the Protocol-defined Virologic Failure (PDVF) Criteria at Week 96   [ Time Frame: Baseline to Week 96 ]

12.  Secondary:   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) ]

13.  Secondary:   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) ]

14.  Secondary:   Number of Participants Who Reported a Suspected Abacavir Hypersensitivity Reaction (ABC HSR) Reaction or Proximal Renal Tubule Dysfunction   [ Time Frame: Baseline through 96 weeks ]


  Serious Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Reporting Groups
  Description
Abacavir/Lamivudine (ABC/3TC) + Lopinavir/Ritonavir (LPV/RTV) 1 tablet (600mg/300mg) ABC/3TC + 800mg/200mg LPV/RTV combination therapy once daily
Tenofovir/Emtricitabine (TDF/FTC) + LPV/RTV 1 tablet (300mg/200mg) TDF/FTC + 800mg/200mg LPV/RTV combination therapy once daily

Serious Adverse Events
    Abacavir/Lamivudine (ABC/3TC) + Lopinavir/Ritonavir (LPV/RTV)     Tenofovir/Emtricitabine (TDF/FTC) + LPV/RTV  
Total, serious adverse events      
# participants affected     42     45  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     2/343 (0.58%)     2/345 (0.58%)  
Cardiac disorders      
Cardiac arrest † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Cardiac failure congestive † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Cardiopulmonary failure † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Endocrine disorders      
Adrenal insufficiency † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Eye disorders      
Diabetic retinopathy † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Gastrointestinal disorders      
Haematemesis † 1    
# participants affected / at risk     1/343 (0.29%)     1/345 (0.29%)  
Nausea † 1    
# participants affected / at risk     0/343 (0.00%)     2/345 (0.58%)  
Ascites † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Diarrhoea † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Gastrointestinal haemorrhage † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Haemorrhoids † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Proctitis † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Vomiting † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
General disorders      
Chest pain † 1    
# participants affected / at risk     2/343 (0.58%)     0/345 (0.00%)  
Pyrexia † 1    
# participants affected / at risk     1/343 (0.29%)     1/345 (0.29%)  
Death † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Gait disturbance † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Non-cardiac chest pain † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Hepatobiliary disorders      
Cholecystitis acute † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Hepatitic cirrhosis † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Hepatosplenomegaly † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Hepatotoxicity † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Immune system disorders      
Drug hypersensitivity † 1    
# participants affected / at risk     12/343 (3.50%)     3/345 (0.87%)  
Hypersensitivity † 1    
# participants affected / at risk     2/343 (0.58%)     0/345 (0.00%)  
Immune reconstitution syndrome † 1    
# participants affected / at risk     2/343 (0.58%)     0/345 (0.00%)  
Infections and infestations      
Pneumonia † 1    
# participants affected / at risk     3/343 (0.87%)     4/345 (1.16%)  
Gastroenteritis † 1    
# participants affected / at risk     1/343 (0.29%)     1/345 (0.29%)  
Meningitis cryptococcal † 1    
# participants affected / at risk     1/343 (0.29%)     1/345 (0.29%)  
Mycobacterium avium complex infection † 1    
# participants affected / at risk     0/343 (0.00%)     2/345 (0.58%)  
Pneumocystis jiroveci pneumonia † 1    
# participants affected / at risk     1/343 (0.29%)     1/345 (0.29%)  
Staphylococcal infection † 1    
# participants affected / at risk     1/343 (0.29%)     1/345 (0.29%)  
Abscess † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Abscess limb † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Bronchitis † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Cellulitis † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Cryptococcal fungaemia † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Encephalitis viral † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Gastroenteritis viral † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Helicobacter infection † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Kidney infection † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Meningitis viral † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Perianal abscess † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Perirectal abscess † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Pharyngitis streptococcal † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Pneumonia bacterial † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Progressive multifocal leukoencephalopathy † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Sepsis † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Staphylococcal bacteraemia † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Tonsilitis streptococcal † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Tuberculosis † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Upper respiratory tract infection † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Injury, poisoning and procedural complications      
Concussion † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Fall † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Head injury † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Laceration † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Investigations      
Creatinine renal clearance decreased † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Metabolism and nutrition disorders      
Dehydration † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Musculoskeletal and connective tissue disorders      
Intervertebral disc protrusion † 1    
# participants affected / at risk     1/343 (0.29%)     1/345 (0.29%)  
Back pain † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Lumbar spinal stenosis † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Tendon pain † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Kaposi’s sarcoma † 1    
# participants affected / at risk     2/343 (0.58%)     0/345 (0.00%)  
Carcinoid tumor † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Hodgkin’s disease † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Malignant melanoma in situ † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Non-Hodgkin’s lymphoma † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Renal cell carcinoma † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Nervous system disorders      
Transient ischaemic attack † 1    
# participants affected / at risk     1/343 (0.29%)     1/345 (0.29%)  
Balance disorder † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Brain mass † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Brain stem infarction † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Cerebrovascular accident † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Migraine † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Syncope † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Pregnancy, puerperium and perinatal conditions      
Ectopic pregnancy † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Psychiatric disorders      
Dependence † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Depression † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Major depression † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Mental status changes † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Suicide attempt † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Renal and urinary disorders      
Haematuria † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Renal failure † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Renal failure acute † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Respiratory, thoracic and mediastinal disorders      
Pulmonary embolism † 1    
# participants affected / at risk     1/343 (0.29%)     2/345 (0.58%)  
Bronchial hyperreactivity † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Chronic obstructive pulmonary disease † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Respiratory failure † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Skin and subcutaneous tissue disorders      
Ecchymosis † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Surgical and medical procedures      
Debridement † 1    
# participants affected / at risk     1/343 (0.29%)     0/345 (0.00%)  
Vascular disorders      
Deep vein thrombosis † 1    
# participants affected / at risk     0/343 (0.00%)     2/345 (0.58%)  
Hypertension † 1    
# participants affected / at risk     0/343 (0.00%)     1/345 (0.29%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 10.0




  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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