The Effect of Raltegravir on HIV Decay During Primary and Chronic Infection - Full Text View

Sponsors and Collaborators:	The National Centre in HIV Epidemiology and Clinical Research Merck Sharp and Dohme
Information provided by:	The National Centre in HIV Epidemiology and Clinical Research
ClinicalTrials.gov Identifier:	NCT00641641

Purpose

The purpose of this study is to measure the decay characteristics of HIV in the blood of patients after taking a combination of anti-HIV drugs, which includes a new class of anti-HIV drug, an integrase inhibitor. This study explores how this new combination of therapy reduces virus in various compartments of the body and immune system.

Condition	Intervention
Primary HIV (Acute or Early) Chronic HIV Infection	Drug: Tenofovir disoproxil fumarate and emtricitabine (TDF/FTC; Truvada) plus the integrase inhibitor, raltegravir.

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	An Open Label Study to Examine the Characteristics of HIV Decay Following Introduction of Combination Antiretroviral Therapy Including Raltegravir During Primary and Chronic HIV Infection

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Raltegravir Truvada

U.S. FDA Resources

Further study details as provided by The National Centre in HIV Epidemiology and Clinical Research:

Primary Outcome Measures:

Viral RNA decay characteristics in plasma as determined by an ultrasensitive HIV RNA PCR with a limit of detection of 0.4 copies/ml. The decay curves will be compared between the two treatment groups. [ Time Frame: 24 times within 156 weeks. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the absolute levels and decay characteristics of: 1. Total HIV DNA in peripheral blood mononuclear cells (PBMC). [ Time Frame: 24 times within 156 weeks ] [ Designated as safety issue: No ]
To assess the absolute levels and decay characteristics of: 2. Total HIV DNA in CD4+ T lymphocytes. [ Time Frame: 24 times within 156 weeks ] [ Designated as safety issue: No ]
To assess the absolute levels and decay characteristics of: 3. Integrated HIV DNA in PBMC and CD4+ T lymphocytes. [ Time Frame: 8 times within 156 weeks ] [ Designated as safety issue: No ]
To assess the absolute levels and decay characteristics of: 4. Episomal HIV DNA in PBMC and CD4+ T lymphocytes. [ Time Frame: 8 times within 156 weeks ] [ Designated as safety issue: No ]
To assess the absolute levels and decay characteristics of: 5. Total DNA, integrated and episomal DNA in resting CD4+ T cells (CD3+, CD4+, CD69-, CD25-, HLADR-). [ Time Frame: 8 times within 156 weeks ] [ Designated as safety issue: No ]
To assess the absolute levels and decay characteristics of: 6. Total HIV DNA in CD4+ T lymphocytes in lymphoid tissue. (Week 0 and 52) [ Time Frame: 3 times within 156 weeks ] [ Designated as safety issue: No ]

Enrollment:	16
Study Start Date:	March 2008
Estimated Study Completion Date:	November 2011
Estimated Primary Completion Date:	October 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Drug intervention: Experimental Drug intervention	Drug: Tenofovir disoproxil fumarate and emtricitabine (TDF/FTC; Truvada) plus the integrase inhibitor, raltegravir. At Day 0, subjects will be required to start treatment consisting of Truvada (FTC 200mg + TDF 300mg once daily) plus raltegravir (400mg twice daily).

Detailed Description:

The study is an open-label study of 3-years duration. This study will be conducted at 4 study sites in Sydney, Australia. Sixteen participants will be recruited comprising 8 participants diagnosed with primary HIV infection (Cohort A) and 8 individuals with chronic HIV infection (Cohort B). All patients must be antiretroviral therapy (ART) naïve and will commence a regimen of combination ART consisting of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC; Truvada) plus the integrase inhibitor, raltegravir. Subjects will be followed for three years with intensive quantification of both plasma RNA and cell associated DNA viral species.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age at least 18 years.
Provision of written, informed consent.
Screening plasma HIV RNA > 10,000 copies/mL.
Screening CD4+ T lymphocyte count > 100 x 10^6)/L.
No previous antiretroviral therapy.
Haemoglobin > 115 g/L (female) or > 130 g/L (male).
Absolute neutrophil count > 1 x 10^9/L.
Platelet count > 100 x 10^9/L
Serum bilirubin < 1.5 x ULN.
Serum alkaline phosphatase < 3 X ULN.
Serum aspartate aminotransferase (AST) < 3 X ULN.
Serum alanine aminotransferase (ALT) < 3 X ULN.
Creatinine clearance > 50mL/min (Creatinine clearance (mL/min) =140 - age x weight creatinine Multiply the result by 1.2 for men).

Cohort A: Primary HIV infection:

Documented acute or early infection diagnosed by:

Acute infection:

< 3 bands on Western Blot and any one of: i. positive p24 antigen ii. positive proviral DNA

Early infection:

i. Positive detuned or BED ELISA result OR ii. Previously negative serology within 6 months of confirmed positive serology.

Cohort B: Chronic HIV infection:

Documented HIV-infection of at least 12 months duration.

Exclusion Criteria:

Pregnancy or breastfeeding.
Receipt of investigational products within 1 month of study entry.
Receipt of any of the following within 6 months of study entry:
- interferon alpha or gamma
- oral corticosteroids (inhaled or topical corticosteroids are permitted)
- cyclosporin
- alkylating agents
- other immunosuppressive agents
- rifampin
- phenytoin
- phenobarbital
Documented genotypic (IAS 2007) resistance to tenofovir or emtricitabine from any HIV drug resistance test.
Any medications contraindicated with Truvada or raltegravir.
Significant intercurrent illnesses apart from HIV infection such as viral hepatitis (diagnosed by core hepatitis B antigen and/or positive hepatitis B PCR or positive hepatitis C PCR) or any other condition which in the opinion of the investigator would compromise participation in the study.
History of non-traumatic osteoporotic fracture.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00641641

Locations

Australia, New South Wales
St Vincent's Hospital
Darlinghurst, Sydney, New South Wales, Australia, 2010
407 Doctors
Sydney, New South Wales, Australia, 2010
Holdsworth House Medical Practice
Sydney, New South Wales, Australia, 2010
Taylor Square Private Clinic
Sydney, New South Wales, Australia, 2010

Sponsors and Collaborators

The National Centre in HIV Epidemiology and Clinical Research

Merck Sharp and Dohme

Investigators

Principal Investigator:

Anthony Kelleher, MBBS (Hons) PhD, FRACP, FRCPA

The National Centre in HIV Epidemiology and Clinical Research

More Information

No publications provided

Responsible Party:	National Centre in HIV Epidemiology and Clinical Research ( Associate Professor Anthony Kelleher )
Study ID Numbers:	PINT01
Study First Received:	February 28, 2008
Last Updated:	March 31, 2009
ClinicalTrials.gov Identifier:	NCT00641641 History of Changes
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by The National Centre in HIV Epidemiology and Clinical Research:

Viral compartments
integrase inhibitor therapy
viral species

Study placed in the following topic categories:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Antiviral Agents
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Virus Diseases

Emtricitabine
Anti-Retroviral Agents
HIV Infections
Integrase Inhibitors
Sexually Transmitted Diseases
Tenofovir
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:

Communicable Diseases
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Reverse Transcriptase Inhibitors
Emtricitabine
Anti-Retroviral Agents
Integrase Inhibitors
Therapeutic Uses
Tenofovir
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

Tenofovir disoproxil
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on September 10, 2009