Pilot Study of Raltegravir/Truvada Versus Efavirenz/Truvada for Adults With Acute IV-1 Infection

Pilot Study of Raltegravir/Tenofovir/Emtricitabine Versus Efavirenz/Tenofovir/Emtricitabine for Adults With Acute HIV-1 Infection: Exploring the Role of Integrase Inhibition in Early HIV Pathogenesis

This is a single-site, investigator-initiated, open-label, randomized/controlled clinical trial to compare the viral load response in plasma (and, in a subset of subjects, in gastrointestinal lymphoid tissue reservoirs) in subjects with acute/early HIV-1 infection treated with 12 weeks of raltegravir-based versus efavirenz-based ART (each combined with tenofovir/emtricitabine). Subjects will receive a self-limited course of therapy rather than a commitment to life-long HAART, as has been the experimental approach in a variety of clinical protocols in the United States and Europe. Subjects will complete a 12 week course of therapy, and those who meet treatment-response and safety criteria will then undergo a similarly intensive period of virology and immunology monitoring to compare the timing and dynamics of any observed virologic rebound following the treatment intervention.

Study Overview

• Status: Completed
• Conditions: Acute HIV Infection
• Intervention / Treatment: Drug: Efavirenz; Drug: Raltegravir; Drug: Emtricitibine; Drug: Tenofovir disoproxil twice daily; Drug: Tenofovir disoproxil once daily

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB 1917 Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects 19 years of age or older who meet the NIH Acute Infection and Early Disease Research Program (AIEDRP) definition of acute or early HIV-1 infection. Briefly, acute HIV-1 infection is defined as > 5000 copies per milliliter of HIV RNA and one of the following documented within a 7 day period of the initial positive PCR-based assay: 1) a negative HIV-1 EIA or 2) a positive EIA with a negative or indeterminant HIV-1 Western Blot test (interpreted based on current CDC guidelines). For the purposes of this protocol, early HIV-1 infection is defined as detectable HIV RNA by PCR-based assay, a positive HIV EIA, a positive HIV-1 Western blot, and one of the following: 1) a documented negative HIV EIA in the preceding 6 months or 2) an HIV detuned EIA standardized optical density measurement (defined as sample OD - negative control OD/ positive control OD) of < 1.0 within 14 days of the positive HIV EIA (consistent with acute infection occurring in the past 120 days).

Exclusion Criteria:

• Lack consistent evidence of seroconversion or documented appropriate antibody testing for persistent HIV infection during the screening and early follow-up period.
• Prior receipt of antiretroviral therapy.
• Serum creatinine > 2.0 x upper limit of normal or a calculated creatinine clearance at time of screening < 30 mL/min (and 0.85X this value for females).
• Alkaline phosphatase >5 x upper limit of normal.
• AST (SGOT) and ALT (SGPT) > 5 x upper limit of normal. Repeat of a laboratory screening test will be allowed for test results that are unexpected based on documented prior laboratory results or to monitor declining trends that may relate to the primary retroviral syndrome.
• Have any severe medical illness that the investigators feel will interfere with the ability to take therapy or that will result in making therapy too risky for the subject. This includes active tuberculosis treatment, severe liver disease due to alcoholism or viral hepatitis, or unstable cardiovascular or cerebrovascular disease.
• Have significant psychiatric illness or ongoing substance abuse that, in the opinion of the investigators, would compromise the ability of the subject to provide adequate informed consent or to adhere to the study procedures safely and consistently.
• Women who are pregnant or actively breastfeeding at the time of screening.
• Men or women who are actively attempting to become pregnant, or who are unable or unwilling to institute adequate birth control measures during the entire course of this treatment protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1; Raltegravir plus Truvada	Drug: Raltegravir; Raltegravir 400 mg. BID; Drug: Emtricitibine; 200mg once daily; Drug: Tenofovir disoproxil twice daily; 300mg twice daily
Active Comparator: Arm 2; Efavirenz plus Truvada	Drug: Efavirenz; 600 mg once daily; Drug: Emtricitibine; 200mg once daily; Drug: Tenofovir disoproxil once daily; 300mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean White Blood Cell Count Between Treatment Groups at 2 Months	Mean WBC count for all subjects as determined by standard lab procedures at 2 months after starting study drug as well as range. The normal number of WBCs in the blood is 4,500-10,000 white blood cells per microliter (mcL).	baseline to 2 months
Mean White Blood Cell Count Between Treatment Groups at 4 Months	Mean WBC count of all subjects as determined by standard lab procedures at 4 months after starting study drug as well as range. The normal number of WBCs in the blood is 4,500-10,000 white blood cells per microliter (mcL).	4 months post baseline
Mean White Blood Cell Count Between Treatment Groups at 6 Months	Mean WBC count of all subjects as determined by standard lab procedures at 6 months after starting study drug as well as range. The normal number of WBCs in the blood is 4,500-10,000 white blood cells per microliter (mcL).	6 months after baseline
Mean White Blood Cell Count Between Treatment Groups at 8 Months	Mean WBC count of all subjects as determined by standard lab procedures at 8 months after starting study drug as well as range. The normal number of WBCs in the blood is 4,500-10,000 white blood cells per microliter (mcL).	8 months after baseline
Mean White Blood Cell Count Between Treatment Groups at 10 Months	Mean WBC count of all subjects as determined by standard lab procedures at 10 months after starting study drug as well as range. The normal number of WBCs in the blood is 4,500-10,000 white blood cells per microliter (mcL).	10 months after baseline
Mean White Blood Cell Count Between Treatment Groups at 12 Months	Mean WBC count of all subjects as determined by standard lab procedures at 12 months after starting study drug as well as range. The normal number of WBCs in the blood is 4,500-10,000 white blood cells per microliter (mcL).	12 months after baseline
Mean White Blood Cell Count Between Treatment Groups at 14 Months	Mean WBC count of all subjects as determined by standard lab procedures at 14 months after starting study drug as well as range. The normal number of WBCs in the blood is 4,500-10,000 white blood cells per microliter (mcL).	14 months after baseline
Mean Hematocrit Between Treatment Groups at 2 Months	Mean hematocrit of all subjects at 2 months after starting study drug. The hematocrit, also known as packed cell volume (PCV) or erythrocyte volume fraction (EVF), is the volume percentage (%) of red blood cells in blood. It is normally 45% for men and 40% for women.	2 months after baseline
Mean Hematocrit Between Treatment Groups at 4 Months	Mean hematocrit of all subjects at 4 months after starting study drug. The hematocrit, also known as packed cell volume (PCV) or erythrocyte volume fraction (EVF), is the volume percentage (%) of red blood cells in blood. It is normally 45% for men and 40% for women.	4 months after baseline
Mean Hematocrit Between Treatment Groups at 6 Months	Mean hematocrit of all subjects at 6 months after starting study drug. The hematocrit, also known as packed cell volume (PCV) or erythrocyte volume fraction (EVF), is the volume percentage (%) of red blood cells in blood. It is normally 45% for men and 40% for women.	6 months after baseline
Mean Hematocrit Between Treatment Groups at 8 Months	Mean hematocrit of all subjects at 8 months after starting study drug. The hematocrit, also known as packed cell volume (PCV) or erythrocyte volume fraction (EVF), is the volume percentage (%) of red blood cells in blood. It is normally 45% for men and 40% for women.	8 months after baseline
Mean Hematocrit Between Treatment Groups at 10 Months	Mean hematocrit of all subjects at 10 months after starting study drug. The hematocrit, also known as packed cell volume (PCV) or erythrocyte volume fraction (EVF), is the volume percentage (%) of red blood cells in blood. It is normally 45% for men and 40% for women.	10 months after baseline
Mean Hematocrit Between Treatment Groups at 12 Months	Mean hematocrit of all subjects at 12 months after starting study drug. The hematocrit, also known as packed cell volume (PCV) or erythrocyte volume fraction (EVF), is the volume percentage (%) of red blood cells in blood. It is normally 45% for men and 40% for women.	12 months after baseline
Mean Hematocrit Between Treatment Groups at 14 Months	Mean hematocrit of all subjects at 14 months after starting study drug. The hematocrit, also known as packed cell volume (PCV) or erythrocyte volume fraction (EVF), is the volume percentage (%) of red blood cells in blood. It is normally 45% for men and 40% for women.	14 months after baseline
Mean Platelet Count Between Treatment Groups at 2 Months	The mean platelet count between treament groups at 2 months after starting study drug. The calculated number of platelets in a volume of blood, usually expressed as platelets per cubic millimeter (cmm) of whole blood. Platelets are the smallest cell-like structures in the blood and are important for blood clotting and plugging damaged blood vessels. Platelet counts are usually done by laboratory machines that also count other blood elements such as the white and red cells. They can also be counted by use of a microscope. Normal platelet counts are in the range of 150,000 to 400,000 per microliter (or 150 - 400 x 100 per liter).	2 months after baseline
Mean Platelet Count Between Treatment Groups at 4 Months	The mean platelet count between treatment groups at 4 months after starting study drug. The calculated number of platelets in a volume of blood, usually expressed as platelets per cubic millimeter (cmm) of whole blood. Platelets are the smallest cell-like structures in the blood and are important for blood clotting and plugging damaged blood vessels. Platelet counts are usually done by laboratory machines that also count other blood elements such as the white and red cells. They can also be counted by use of a microscope. Normal platelet counts are in the range of 150,000 to 400,000 per microliter (or 150 - 400 x 109 per liter).	4 months after baseline
Mean Platelet Count Between Treatment Groups at 6 Months	The mean platelet count between treatment groups at 6 months after starting study drug. The calculated number of platelets in a volume of blood, usually expressed as platelets per cubic millimeter (cmm) of whole blood. Platelets are the smallest cell-like structures in the blood and are important for blood clotting and plugging damaged blood vessels. Platelet counts are usually done by laboratory machines that also count other blood elements such as the white and red cells. They can also be counted by use of a microscope. Normal platelet counts are in the range of 150,000 to 400,000 per microliter (or 150 - 400 x 109 per liter).	6 months after baseline
Mean Platelet Count Between Treatment Groups at 8 Months	The mean platelet count between treatment groups at 8 months after starting study drug. The calculated number of platelets in a volume of blood, usually expressed as platelets per cubic millimeter (cmm) of whole blood. Platelets are the smallest cell-like structures in the blood and are important for blood clotting and plugging damaged blood vessels. Platelet counts are usually done by laboratory machines that also count other blood elements such as the white and red cells. They can also be counted by use of a microscope. Normal platelet counts are in the range of 150,000 to 400,000 per microliter (or 150 - 400 x 109 per liter).	8 months after baseline
Mean Platelet Count Between Treatment Groups at 10 Months	The mean platelet count between treatment groups at 10 months after starting study drug. The calculated number of platelets in a volume of blood, usually expressed as platelets per cubic millimeter (cmm) of whole blood. Platelets are the smallest cell-like structures in the blood and are important for blood clotting and plugging damaged blood vessels. Platelet counts are usually done by laboratory machines that also count other blood elements such as the white and red cells. They can also be counted by use of a microscope. Normal platelet counts are in the range of 150,000 to 400,000 per microliter (or 150 - 400 x 109 per liter).	10 months after baseline
Mean Platelet Count Between Treatment Groups at 12 Months	The mean platelet count between treatment groups at 12 months after starting study drug. The calculated number of platelets in a volume of blood, usually expressed as platelets per cubic millimeter (cmm) of whole blood. Platelets are the smallest cell-like structures in the blood and are important for blood clotting and plugging damaged blood vessels. Platelet counts are usually done by laboratory machines that also count other blood elements such as the white and red cells. They can also be counted by use of a microscope. Normal platelet counts are in the range of 150,000 to 400,000 per microliter (or 150 - 400 x 109 per liter).	12 months after baseline
Mean Platelet Count Between Treatment Groups at 14 Months	The mean platelet count between treatment groups at 14 months after starting study drug. The calculated number of platelets in a volume of blood, usually expressed as platelets per cubic millimeter (cmm) of whole blood. Platelets are the smallest cell-like structures in the blood and are important for blood clotting and plugging damaged blood vessels. Platelet counts are usually done by laboratory machines that also count other blood elements such as the white and red cells. They can also be counted by use of a microscope. Normal platelet counts are in the range of 150,000 to 400,000 per microliter (or 150 - 400 x 109 per liter).	4 months after baseline
Mean CD4 Count Between Treatment Groups at 1 Months	Mean CD4 count between groups 1 month after starting study drug. CD4 cells are types of white blood cells called T lymphocytes or T cells that fight infection. CD4 counts are most often used to evaluate the immune system of a person diagnosed with a human immunodeficiency virus (HIV) infection to help stage and monitor progression of the disease and monitor effectiveness of antiretroviral treatment. A CD4 count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). A normal CD4 count ranges from 410-1,590 cells/mm3. Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).	1 month after baseline
Mean CD4 Count Between Treatment Groups at 2 Months	Mean CD4 count between groups 2 months after starting study drug. CD4 cells are types of white blood cells called T lymphocytes or T cells that fight infection. CD4 counts are most often used to evaluate the immune system of a person diagnosed with a human immunodeficiency virus (HIV) infection to help stage and monitor progression of the disease and monitor effectiveness of antiretroviral treatment. A CD4 count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). A normal CD4 count ranges from 410-1,590 cells/mm3 in adults and teens. Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).	2 months after baseline
Mean CD4 Count Between Treatment Groups at 3 Months	Mean CD4 count between groups 3 months after starting study drug. CD4 cells are types of white blood cells called T lymphocytes or T cells that fight infection. CD4 counts are most often used to evaluate the immune system of a person diagnosed with a human immunodeficiency virus (HIV) infection to help stage and monitor progression of the disease and monitor effectiveness of antiretroviral treatment. A CD4 count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). A normal CD4 count ranges from 410-1,590 cells/mm3 in adults and teens. Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).	3 months after baseline
Mean CD4 Count Between Treatment Groups at 4 Months	Mean CD4 count between groups 4 months after starting study drug. CD4 cells are types of white blood cells called T lymphocytes or T cells that fight infection. CD4 counts are most often used to evaluate the immune system of a person diagnosed with a human immunodeficiency virus (HIV) infection to help stage and monitor progression of the disease and monitor effectiveness of antiretroviral treatment. A CD4 count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). A normal CD4 count ranges from 410-1,590 cells/mm3 in adults and teens. Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).	4 months after baseline
Mean CD4 Count Between Treatment Groups at 5 Months	Mean CD4 count between groups 5 months after starting study drug. CD4 cells are types of white blood cells called T lymphocytes or T cells that fight infection. CD4 counts are most often used to evaluate the immune system of a person diagnosed with a human immunodeficiency virus (HIV) infection to help stage and monitor progression of the disease and monitor effectiveness of antiretroviral treatment. A CD4 count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). A normal CD4 count ranges from 410-1,590 cells/mm3 in adults and teens. Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).	5 months after baseline
Mean CD4 Count Between Treatment Groups at 6 Months	Mean CD4 count between groups 6 months after starting study drug. CD4 cells are types of white blood cells called T lymphocytes or T cells that fight infection. CD4 counts are most often used to evaluate the immune system of a person diagnosed with a human immunodeficiency virus (HIV) infection to help stage and monitor progression of the disease and monitor effectiveness of antiretroviral treatment. A CD4 count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). A normal CD4 count ranges from 410-1,590 cells/mm3 in adults and teens. Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).	6 months after baseline
Mean CD4 Count Between Treatment Groups at 7 Months	Mean CD4 count between groups 7 months after starting study drug. CD4 cells are types of white blood cells called T lymphocytes or T cells that fight infection. CD4 counts are most often used to evaluate the immune system of a person diagnosed with a human immunodeficiency virus (HIV) infection to help stage and monitor progression of the disease and monitor effectiveness of antiretroviral treatment. A CD4 count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). A normal CD4 count ranges from 410-1,590 cells/mm3 in adults and teens. Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).	7 months after baseline
Mean CD4 Count Between Treatment Groups at 8 Months	Mean CD4 count between groups 8 months after starting study drug. CD4 cells are types of white blood cells called T lymphocytes or T cells that fight infection. CD4 counts are most often used to evaluate the immune system of a person diagnosed with a human immunodeficiency virus (HIV) infection to help stage and monitor progression of the disease and monitor effectiveness of antiretroviral treatment. A CD4 count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). A normal CD4 count ranges from 410-1,590 cells/mm3 in adults and teens. Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).	8 months after baseline
Mean CD4 Count Between Treatment Groups at 9 Months	Mean CD4 count between groups 9 months after starting study drug. CD4 cells are types of white blood cells called T lymphocytes or T cells that fight infection. CD4 counts are most often used to evaluate the immune system of a person diagnosed with a human immunodeficiency virus (HIV) infection to help stage and monitor progression of the disease and monitor effectiveness of antiretroviral treatment. A CD4 count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). A normal CD4 count ranges from 410-1,590 cells/mm3 in adults and teens. Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).	9 months after baseline
Mean CD4 Count Between Treatment Groups at 10 Months	Mean CD4 count between groups 10 months after starting study drug. CD4 cells are types of white blood cells called T lymphocytes or T cells that fight infection. CD4 counts are most often used to evaluate the immune system of a person diagnosed with a human immunodeficiency virus (HIV) infection to help stage and monitor progression of the disease and monitor effectiveness of antiretroviral treatment. A CD4 count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). A normal CD4 count ranges from 410-1,590 cells/mm3 in adults and teens. Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).	10 months after baseline
Mean CD4 Count Between Treatment Groups at 11 Months	Mean CD4 count between groups 11 months after of starting study drug. CD4 cells are types of white blood cells called T lymphocytes or T cells that fight infection. CD4 counts are most often used to evaluate the immune system of a person diagnosed with a human immunodeficiency virus (HIV) infection to help stage and monitor progression of the disease and monitor effectiveness of antiretroviral treatment. A CD4 count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). A normal CD4 count ranges from 410-1,590 cells/mm3 in adults and teens. Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).	11 months after baseline

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Sonya Heath, M. D., Department of Medicine Divison of Infectious Disease

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: August 12, 2008
• First Submitted That Met QC Criteria: August 13, 2008
• First Posted (Estimate): August 14, 2008

Study Record Updates

• Last Update Posted (Estimate): May 30, 2016
• Last Update Submitted That Met QC Criteria: April 25, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Integrase Inhibitors; Integrase Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Raltegravir Potassium; Efavirenz
• Other Study ID Numbers: F080416007