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Study of Viral Load Decay Rates in HIV Infected Participants Starting Treatment With Raltegravir (RAL) and Emtricitabine/Tenofovir Disoproxil Fumarate (TDF)

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Raltegravir
Emtricitabine/tenofovir disoproxil fumarate
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV Integrase Inhibitors, HIV Nucleoside Reverse Transcriptase Inhibitors, Treatment Naive, Viral Load

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • HIV infected
  • Antiretroviral treatment naive
  • Viral load at least 10,000 and less than 300,000 copies/ml within 42 days prior to study entry
  • Agree to use appropriate form of contraception. More information on this criterion can be found in the protocol.

Exclusion Criteria:

  • Received HIV-specific immunizations within 6 months prior to study entry
  • Received immunizations within 6 months prior to study entry
  • Known allergy or sensitivity to study drugs
  • Any participant with an acute AIDS-defining opportunistic infection (OI) who is not clinically stable or who has not been on therapy for the OI for at least 30 days prior to study entry
  • Treatment with immune modulators or any investigational therapy within 30 days prior to study entry
  • Evidence of HIV seroconversion within 6 months prior to study entry
  • Illness requiring systemic treatment and/or hospitalization
  • Substance abuse that, in the opinion of the investigator, would interfere with adherence to study requirements
  • Requirement for any current medications that are prohibited with any study medication. More information on this criterion can be found in the protocol.
  • Evidence of any major resistance-associated mutation on any genotype performed prior to study entry or at the time of screening. More information on this criterion can be found in the protocol.
  • Abnormal laboratory values. More information on this criterion can be found in the protocol.
  • Pregnant or breastfeeding

Sites / Locations

  • UCSD Antiviral Research Center CRS
  • University of Colorado Hospital CRS
  • Northwestern University CRS
  • IHV Baltimore Treatment CRS
  • Johns Hopkins University CRS
  • Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
  • Washington University Therapeutics (WT) CRS
  • Harlem ACTG CRS
  • Trillium Health ACTG CRS
  • Univ. of Rochester ACTG CRS
  • MetroHealth CRS
  • Ohio State University CRS
  • The Miriam Hospital Clinical Research Site (TMH CRS) CRS
  • Vanderbilt Therapeutics (VT) CRS
  • Houston AIDS Research Team CRS

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Oral RAL and FTC/TDF for 72 weeks

Outcomes

Primary Outcome Measures

Viral load decay rates

Secondary Outcome Measures

Viral load decay rates
Proportion of participants with a viral load less than 50 copies/ml
Safety and tolerability. More information on this criterion can be found in the protocol.
CD4 and CD8 count
Resistance mutations to RAL, FTC, and TDF
Minimum concentration (Cmin) for RAL, FTC, and TDF
Changes in viral load
Self-reported adherence
Cell-associated proviral DNA, LTR circular DNA, and integrated proviral DNA
Viral load

Full Information

First Posted
April 16, 2008
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Adult AIDS Clinical Trials Group
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1. Study Identification

Unique Protocol Identification Number
NCT00660972
Brief Title
Study of Viral Load Decay Rates in HIV Infected Participants Starting Treatment With Raltegravir (RAL) and Emtricitabine/Tenofovir Disoproxil Fumarate (TDF)
Official Title
First-Phase Viral Decay Rates in Treatment-Naive Subjects Initiating Treatment With Raltegravir (RAL) and Emtricitabine (FTC)/Tenofovir Disoproxil Fumarate (TDF): A Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
January 2009 (Actual)
Study Completion Date
April 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Adult AIDS Clinical Trials Group

4. Oversight

5. Study Description

Brief Summary
The HIV integrase inhibitor, raltegravir (RAL), which was recently approved by the FDA, has been shown in several trials to be highly effective. The purpose of this trial is to estimate the viral load decay rate in treatment-naive HIV infected participants receiving RAL and emtricitabine/tenofovir disoproxil fumarate (FTC/TDF).
Detailed Description
Recent data suggests that early virologic response to HIV interventions may be predictive of long-term virologic outcomes. Defining early decay in viral load through carefully performed studies of viral dynamics may be a useful tool for assessing the likely outcome of long-term treatment. It may also be a useful screening tool to define which combinations should be studied further. In this trial, the viral load decay rate will be estimated in HIV infected, treatment-naive participants receiving RAL and FTC/TDF. This study will last approximately 72 weeks. All participants will take RAL and FTC/TDF for 72 weeks. RAL will be provided by the study. FTC/TDF will not be provided. This study will consist of 16 study visits. These visits will occur at study entry, Days 2, 7, 10, 14, 21, 28, and 56, and Weeks 12, 16, 20, 24, 36, 48, 60, and 72. Blood collection and pharmacokinetic studies will occur at all study visits. Self-reported adherence assessments will be submitted at each visit. A targeted physical exam will occur at most visits. Liver function tests and urine collection will occur at select visits. Pregnancy tests will occur whenever pregnancy is suspected.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV Integrase Inhibitors, HIV Nucleoside Reverse Transcriptase Inhibitors, Treatment Naive, Viral Load

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Oral RAL and FTC/TDF for 72 weeks
Intervention Type
Drug
Intervention Name(s)
Raltegravir
Other Intervention Name(s)
RAL
Intervention Description
400 mg tablet taken orally twice daily
Intervention Type
Drug
Intervention Name(s)
Emtricitabine/tenofovir disoproxil fumarate
Other Intervention Name(s)
FTC/TDF
Intervention Description
Fixed dose tablet containing 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate taken once daily. FTC/TDF will not be provided by the study and must be obtained by the particpant's health care provider.
Primary Outcome Measure Information:
Title
Viral load decay rates
Time Frame
Through Day 56
Secondary Outcome Measure Information:
Title
Viral load decay rates
Time Frame
From Weeks 24 to 72
Title
Proportion of participants with a viral load less than 50 copies/ml
Time Frame
At Weeks 24, 48, and 72
Title
Safety and tolerability. More information on this criterion can be found in the protocol.
Time Frame
Throughout study
Title
CD4 and CD8 count
Time Frame
Throughout study
Title
Resistance mutations to RAL, FTC, and TDF
Time Frame
Throughout study
Title
Minimum concentration (Cmin) for RAL, FTC, and TDF
Time Frame
Throughout study
Title
Changes in viral load
Time Frame
At Day 7
Title
Self-reported adherence
Time Frame
Throughout study
Title
Cell-associated proviral DNA, LTR circular DNA, and integrated proviral DNA
Time Frame
Throughout study
Title
Viral load
Time Frame
From Week 24 to Week 72

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: HIV infected Antiretroviral treatment naive Viral load at least 10,000 and less than 300,000 copies/ml within 42 days prior to study entry Agree to use appropriate form of contraception. More information on this criterion can be found in the protocol. Exclusion Criteria: Received HIV-specific immunizations within 6 months prior to study entry Received immunizations within 6 months prior to study entry Known allergy or sensitivity to study drugs Any participant with an acute AIDS-defining opportunistic infection (OI) who is not clinically stable or who has not been on therapy for the OI for at least 30 days prior to study entry Treatment with immune modulators or any investigational therapy within 30 days prior to study entry Evidence of HIV seroconversion within 6 months prior to study entry Illness requiring systemic treatment and/or hospitalization Substance abuse that, in the opinion of the investigator, would interfere with adherence to study requirements Requirement for any current medications that are prohibited with any study medication. More information on this criterion can be found in the protocol. Evidence of any major resistance-associated mutation on any genotype performed prior to study entry or at the time of screening. More information on this criterion can be found in the protocol. Abnormal laboratory values. More information on this criterion can be found in the protocol. Pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adriana Andrade, MD, MPH
Organizational Affiliation
Johns Hopkins University
Official's Role
Study Chair
Facility Information:
Facility Name
UCSD Antiviral Research Center CRS
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
University of Colorado Hospital CRS
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
IHV Baltimore Treatment CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Johns Hopkins University CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Washington University Therapeutics (WT) CRS
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110-1010
Country
United States
Facility Name
Harlem ACTG CRS
City
New York
State/Province
New York
ZIP/Postal Code
10037
Country
United States
Facility Name
Trillium Health ACTG CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14607
Country
United States
Facility Name
Univ. of Rochester ACTG CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
MetroHealth CRS
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Ohio State University CRS
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
The Miriam Hospital Clinical Research Site (TMH CRS) CRS
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
Vanderbilt Therapeutics (VT) CRS
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37204
Country
United States
Facility Name
Houston AIDS Research Team CRS
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18321239
Citation
Evering TH, Markowitz M. Raltegravir: an integrase inhibitor for HIV-1. Expert Opin Investig Drugs. 2008 Mar;17(3):413-22. doi: 10.1517/13543784.17.3.413.
Results Reference
background
PubMed Identifier
18362342
Citation
Sedaghat AR, Dinoso JB, Shen L, Wilke CO, Siliciano RF. Decay dynamics of HIV-1 depend on the inhibited stages of the viral life cycle. Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4832-7. doi: 10.1073/pnas.0711372105. Epub 2008 Mar 24.
Results Reference
background
PubMed Identifier
27740536
Citation
Funderburg NT, Xu D, Playford MP, Joshi AA, Andrade A, Kuritzkes DR, Lederman MM, Mehta NN. Treatment of HIV infection with a raltegravir-based regimen increases LDL levels, but improves HDL cholesterol efflux capacity. Antivir Ther. 2017;22(1):71-75. doi: 10.3851/IMP3091. Epub 2016 Oct 14.
Results Reference
derived
PubMed Identifier
24367599
Citation
Funderburg NT, Andrade A, Chan ES, Rosenkranz SL, Lu D, Clagett B, Pilch-Cooper HA, Rodriguez B, Feinberg J, Daar E, Mellors J, Kuritzkes D, Jacobson JM, Lederman MM. Dynamics of immune reconstitution and activation markers in HIV+ treatment-naive patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine. PLoS One. 2013 Dec 18;8(12):e83514. doi: 10.1371/journal.pone.0083514. eCollection 2013.
Results Reference
derived

Learn more about this trial

Study of Viral Load Decay Rates in HIV Infected Participants Starting Treatment With Raltegravir (RAL) and Emtricitabine/Tenofovir Disoproxil Fumarate (TDF)

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