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

Tracking Information
First Submitted Date ICMJE	August 12, 2008
First Posted Date ICMJE	August 14, 2008
Results First Submitted Date	January 5, 2016
Results First Posted Date	May 30, 2016
Last Update Posted Date	May 30, 2016
Study Start Date ICMJE	September 2008
Actual Primary Completion Date	August 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 25, 2016)	Mean White Blood Cell Count Between Treatment Groups at 2 Months [ Time Frame: baseline to 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).; Mean White Blood Cell Count Between Treatment Groups at 4 Months [ Time Frame: 4 months post baseline ]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).; Mean White Blood Cell Count Between Treatment Groups at 6 Months [ Time Frame: 6 months after baseline ]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).; Mean White Blood Cell Count Between Treatment Groups at 8 Months [ Time Frame: 8 months after baseline ]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).; Mean White Blood Cell Count Between Treatment Groups at 10 Months [ Time Frame: 10 months after baseline ]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).; Mean White Blood Cell Count Between Treatment Groups at 12 Months [ Time Frame: 12 months after baseline ]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).; Mean White Blood Cell Count Between Treatment Groups at 14 Months [ Time Frame: 14 months after baseline ]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).; Mean Hematocrit Between Treatment Groups at 2 Months [ Time Frame: 2 months after baseline ]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.; Mean Hematocrit Between Treatment Groups at 4 Months [ Time Frame: 4 months after baseline ]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.; Mean Hematocrit Between Treatment Groups at 6 Months [ Time Frame: 6 months after baseline ]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.; Mean Hematocrit Between Treatment Groups at 8 Months [ Time Frame: 8 months after baseline ]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.; Mean Hematocrit Between Treatment Groups at 10 Months [ Time Frame: 10 months after baseline ]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.; Mean Hematocrit Between Treatment Groups at 12 Months [ Time Frame: 12 months after baseline ]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.; Mean Hematocrit Between Treatment Groups at 14 Months [ Time Frame: 14 months after baseline ]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.; Mean Platelet Count Between Treatment Groups at 2 Months [ Time Frame: 2 months after baseline ]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).; Mean Platelet Count Between Treatment Groups at 4 Months [ Time Frame: 4 months after baseline ]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).; Mean Platelet Count Between Treatment Groups at 6 Months [ Time Frame: 6 months after baseline ]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).; Mean Platelet Count Between Treatment Groups at 8 Months [ Time Frame: 8 months after baseline ]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).; Mean Platelet Count Between Treatment Groups at 10 Months [ Time Frame: 10 months after baseline ]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).; Mean Platelet Count Between Treatment Groups at 12 Months [ Time Frame: 12 months after baseline ]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).; Mean Platelet Count Between Treatment Groups at 14 Months [ Time Frame: 4 months after baseline ]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).; Mean CD4 Count Between Treatment Groups at 1 Months [ Time Frame: 1 month after baseline ]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).; Mean CD4 Count Between Treatment Groups at 2 Months [ Time Frame: 2 months after baseline ]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).; Mean CD4 Count Between Treatment Groups at 3 Months [ Time Frame: 3 months after baseline ]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).; Mean CD4 Count Between Treatment Groups at 4 Months [ Time Frame: 4 months after baseline ]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).; Mean CD4 Count Between Treatment Groups at 5 Months [ Time Frame: 5 months after baseline ]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).; Mean CD4 Count Between Treatment Groups at 6 Months [ Time Frame: 6 months after baseline ]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).; Mean CD4 Count Between Treatment Groups at 7 Months [ Time Frame: 7 months after baseline ]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).; Mean CD4 Count Between Treatment Groups at 8 Months [ Time Frame: 8 months after baseline ]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).; Mean CD4 Count Between Treatment Groups at 9 Months [ Time Frame: 9 months after baseline ]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).; Mean CD4 Count Between Treatment Groups at 10 Months [ Time Frame: 10 months after baseline ]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).; Mean CD4 Count Between Treatment Groups at 11 Months [ Time Frame: 11 months after baseline ]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).
Original Primary Outcome Measures ICMJE; (submitted: August 13, 2008)	RNA, CBC and CD4 results [ Time Frame: All CBC, CD4 and safety labs realtime, RNA results realtime at least every 2 months ]
Change History	Complete list of historical versions of study NCT00734344 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Pilot Study of Raltegravir/Truvada Versus Efavirenz/Truvada for Adults With Acute IV-1 Infection
Official Title ICMJE	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
Brief Summary	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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Acute HIV Infection
Intervention ICMJE	Drug: Raltegravir Raltegravir 400 mg. BID; Drug: Efavirenz 600 mg once daily; Drug: Emtricitibine 200mg once daily; Drug: Tenofovir disoproxil once daily 300mg once daily; Drug: Tenofovir disoproxil twice daily 300mg twice daily
Study Arms	Active Comparator: Arm 1 Raltegravir plus Truvada Interventions: Drug: Raltegravir Drug: Emtricitibine Drug: Tenofovir disoproxil twice daily; Active Comparator: Arm 2 Efavirenz plus Truvada Interventions: Drug: Efavirenz Drug: Emtricitibine Drug: Tenofovir disoproxil once daily
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: April 25, 2016)	18
Original Estimated Enrollment ICMJE; (submitted: August 13, 2008)	20
Actual Study Completion Date	September 2012
Actual Primary Completion Date	August 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	19 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00734344
Other Study ID Numbers ICMJE	F080416007
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Sonya Heath, MD, University of Alabama at Birmingham
Study Sponsor ICMJE	University of Alabama at Birmingham
Collaborators ICMJE	Merck Sharp & Dohme Corp.
Investigators ICMJE	Principal Investigator: Sonya Heath, M. D. Department of Medicine Divison of Infectious Disease
PRS Account	University of Alabama at Birmingham
Verification Date	April 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP