Study of Lopinavir/Ritonavir Tablets Comparing Once-Daily Versus Twice-Daily Administration When Coadministered With Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Antiretroviral-Experienced Human Immunodeficiency Virus Type 1 Infected Subjects

Study Overview
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Brief Summary
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The purpose of this study was to compare the safety, tolerability, and antiviral activity of once-daily (QD) and twice-daily (BID) dosing of the lopinavir/ritonavir (LPV/r) tablet formulation in combination with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in antiretroviral-experienced human immunodeficiency virus type 1 infected subjects with detectable viral load while receiving their current antiretroviral therapy.

Official Title
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A Phase 3, Randomized, Open-Label Study of Lopinavir/Ritonavir (LPV/r) Tablets 800/200 Milligram (mg) Once-Daily (QD) Versus 400/100 mg Twice-Daily (BID) When Coadministered With Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) in Antiretroviral-Experienced, Human Immunodeficiency Virus Type 1 (HIV-1) Infected Subjects

Conditions
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Human Immunodeficiency Virus Infections

Intervention / Treatment
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* Drug: lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
* Drug: lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects were human immunodeficiency virus type 1 (HIV-1) positive, antiretroviral-experienced adults at least 18 years of age currently receiving an antiretroviral regimen which had not changed for at least 12 weeks. Subjects had plasma HIV-1 ribonucleic acid (RNA) levels > 1,000 copies/mL at screening and were not acutely ill. Subject was currently failing his/her antiretroviral regimen with the most recent 2 consecutive prestudy plasma HIV-1 RNA levels > 400 copies/mL with the most recent being > 1000 copies/mL, and in the investigator's opinion, should change therapy Female subjects were nonpregnant and nonlactating. Exclusion Criteria: Subjects were excluded if screening laboratory analyses showed hemoglobin <= 8.0 grams per deciliter. Subjects were excluded if screening laboratory analyses showed absolute neutrophil count <= 750 cells/microliter. Subjects were excluded if screening laboratory analyses showed platelet count <= 50,000 per cubic millimeter. Subjects were excluded if screening laboratory analyses showed alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 5.0 x upper limit of normal (ULN).

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LPV/r 800/200 mg QD Tablet<br> | Drug: lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)<br>* LPV/r 800/200 mg once-daily (QD) tablet<br>* Other names: Kaletra;|
| Active Comparator: LPV/r 400/100 mg BID Tablet<br> | Drug: lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)<br>* LPV/r 400/100 mg twice-daily (BID) tablet<br>* Other names: Kaletra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Responding at Week 48 Based on the Food and Drug Administration (FDA) Time to Loss of Virologic Response (TLOVR) Algorithm | A participant was classified as a responder at the first of 2 consecutive human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) levels <50 copies/mL. The participant continued to be a responder until 2 consecutive values >=50 copies/mL were reached, until the final value if that value was >=50 copies/mL, or until discontinuation or death. | Week 48 (End of Study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/Milliliter (mL) at Week 48 |  | Week 48 (End of Study) | 
| Mean Change From Baseline to Week 48 in Cluster of Differentiation 4 Single-Positive Thymocyte (CD4+ T) Cell Counts |  | Week 48 (End of Study) | 
| Virologic Response (HIV-1 RNA <50 Copies/mL) at Week 48 for Participants With 0-2 Protease Inhibitor Substitutions at Baseline Associated With Reduced Response to Lopinavir/Ritonavir | Substitutions considered in the analysis were L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V as defined in the proposed United States Package Insert. | Week 48 (End of Study) | 
| Percentage of Participants With New Primary Protease Mutations at Week 48 | Emergence of new primary protease inhibitor mutations (i.e., mutations at codons 30, 32, 48, 50, 82, 84, and 90 that were not present at baseline). | Week 48 (End of Study) |