A Study to Compare Anti-HIV Drugs Given Twice a Day or Once a Day, With or Without Direct Observation

Study Overview
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Brief Summary
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Anti-HIV drug therapy works best when the drugs are taken exactly as prescribed by a doctor. Because anti-HIV therapy often involves multiple drugs, some people have difficulty taking them all correctly. The easier it is to take anti-HIV drugs, the more likely people will take them as prescribed and get the best results. This study will see if people are more successful in taking anti-HIV drugs once a day or twice a day. It also will determine if having a health care professional oversee each weekday dose helps people control their HIV infection. The study will compare taking a three-drug combination twice a day versus taking a three-drug combination just once a day. The study will also compare patients taking the drugs on their own to patients taking the drugs in the presence of a clinical worker. Viral load (amount of HIV in the blood) and drug side effects will be measured.

Detailed Description
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While many factors contribute to the success or failure of antiretroviral therapy for HIV, among the most important are factors that influence adherence to a treatment regimen, such as duration of therapy, dosing frequency, pill burden, side effects, and patient behaviors. Inconsistent adherence or nonadherence to antiretroviral therapy can result in suboptimal drug exposure. Suboptimal drug exposure can, in turn, impact short- and long-term patient outcomes by increasing the likelihood of drug resistant HIV mutants and subsequent virologic and clinical failure. It is therefore essential to design treatment regimens that promote long-term adherence to potent antiretroviral therapy. This study will evaluate the relative contribution of reduced-frequency dosing and directly observed therapy on the magnitude and durability of virologic suppression in patients treated with potent antiretroviral therapy. Patients will be randomly assigned to one of three study arms. Arms A, B, and C receive the same daily dosage of lopinavir/ritonavir (LPV/r), emtricitabine (FTC), and stavudine extended release (d4T XR) or tenofovir DF (TDF). In Arm A, drugs are self-administered for 48 weeks; LPV/r is taken twice daily and FTC and d4T XR or TDF once daily. In Arm B, all drugs are self-administered once daily for 48 weeks. In Arm C, drugs are taken once a day under directly observed therapy during Weeks 0-24, and then by self-administration during Weeks 25-48. Adherence to the regimen is measured using an electronic drug monitoring system. Viral load, CD4 and CD8 T cell responses, population pharmacokinetics, and quality of life indicators are measured throughout the study. The tolerability and safety of the treatment regimens are also monitored.

Official Title
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A Randomized, Phase II, Open Label Study to Compare Twice Daily and Once Daily Potent Antiretroviral Therapy and to Compare Self-Administered Therapy and Therapy Administered Under Direct Observation

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: lopinavir/ritonavir
* Drug: emtricitabine
* Drug: stavudine
* Drug: tenofovir DF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria HIV infection Age 13 years or older and have written consent of guardian if under 18 Weigh at least 88 pounds Viral load of 2000 copies/ml or more within 90 days before study entry Have not taken anti-HIV drugs for more than 7 days Agree to use acceptable methods of contraception during the study and for 1 month after stopping the study drugs Exclusion Criteria Pregnant or breastfeeding In jail Sensitive or allergic to any part of the study drugs Treated with acute systemic therapy for a serious infection or other serious medical illness within 7 days prior to study entry, unless the participant has completed 7 days of therapy and is clinically stable Recent serious illness, including pancreatitis or peripheral neuropathy Alcohol or illicit drug abuse Taken any of the following within 14 days before study entry: investigational drugs, anti-HIV vaccines, drugs that may cause pancreatitis or peripheral neuropathy, or drugs that are associated with CYP3A Treated for cancer (not including minimal Kaposi's sarcoma) within 30 days before study entry History of mental illness that might interfere with the study

Ages Eligible for Study
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Minimum Age: 13 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

| Intervention/Treatment |
| --- |
|Drug: lopinavir/ritonavir|nan|
|Drug: emtricitabine|nan|
|Drug: stavudine|nan|
|Drug: tenofovir DF|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lopinavir, HIV-1, Drug Administration Schedule, Stavudine, HIV Protease Inhibitors, Ritonavir, Reverse Transcriptase Inhibitors, Self Care, Viral Load, Emtricitabine, Directly Observed Therapy, Tenofovir Disoproxil Fumarate, Treatment Naive