Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000177358
Ethics application status
Approved
Date submitted
26/02/2008
Date registered
9/04/2008
Date last updated
18/03/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
An open label study to examine the characteristics of Human Immunodeficiency Virus (HIV) decay following introduction of combination antiretroviral therapy including raltegravir during primary and chronic HIV infection
Scientific 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
Universal Trial Number (UTN)
Trial acronym
PINT01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary HIV (acute or early) 2877 0
Chronic HIV infection 2878 0
Condition category
Condition code
Infection 3014 3014 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study is an open-label study of 1-year duration. This study will be conducted at 5 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 one year with intensive quantification of both plasma Ribonucleic acid (RNA) and cell associated Deoxyribonucleic acid (DNA) viral species. Truvada (FTC 200mg + TDF 300mg) once daily plus Isentress (raltegravir 400mg) twice daily.
Intervention code [1] 2632 0
Treatment: Drugs
Comparator / control treatment
No control group. No randomized trial. Pilot study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 3896 0
Viral RNA decay characteristics in plasma as determined by an ultrasensitive HIV RNA Polymerase chain reaction (PCR) with a limit of detection of 0.4 copies/ml.
Timepoint [1] 3896 0
Plasma viral RNA will be measured twice a week for the first 4 weeks then at two weekly intervals until Week 12 then at four weekly intervals until Week 24, then at 8 weekly intervals until Week 40 with a final visit at Week 52. The decay curves will be compared between the two treatment groups.
Secondary outcome [1] 6563 0
To assess the absolute levels and decay characteristics of:
1. Total HIV DNA in peripheral blood mononuclear cells (PBMC).
Timepoint [1] 6563 0
Day 0, week 12 24 52
Secondary outcome [2] 6564 0
To assess the absolute levels and decay characteristics of:
2. Total HIV DNA in CD4+ T lymphocytes.
Timepoint [2] 6564 0
Day 0, week 12 24 52
Secondary outcome [3] 6565 0
To assess the absolute levels and decay characteristics of:
3. Integrated HIV DNA in PBMC and CD4+ T lymphocytes (Week 0, 12, 24 and 52).
Timepoint [3] 6565 0
Screening, day 0, week 0.5 1 1.5 2 1.5 3 3.5 4 6 8 10 12 16 20 24 32 40 52
Secondary outcome [4] 6566 0
4. Episomal HIV DNA in PBMC and CD4+ T lymphocytes.
Timepoint [4] 6566 0
Screening, day 0, week 0.5 1 1.5 2 1.5 3 3.5 4 6 8 10 12 16 20 24 32 40 52
Secondary outcome [5] 6567 0
5. Total DNA, integrated and episomal DNA in resting CD4+ T cells (CD3+, CD4+, CD69-, CD25-, HLADR-).
Timepoint [5] 6567 0
Screening, day 0, week 0.5 1 1.5 2 1.5 3 3.5 4 6 8 10 12 16 20 24 32 40 52
Secondary outcome [6] 6568 0
6. Total HIV DNA in CD4+ T lymphocytes in lymphoid tissue. (Week 0 and 52)
Timepoint [6] 6568 0
Screening - day 0, week 40 - week 52

Eligibility
Key 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 106/L.
•No previous antiretroviral therapy.
•Haemoglobin > 115 g/L (female) or > 130 g/L (male).
•Absolute neutrophil count > 1 x 109/L.
•Platelet count > 100 x 109/L
•Serum bilirubin < 1.5 x upper limit normal (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 B + E + D enzyme linked immuno-sorbent assay (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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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:
o interferon a or ?
o oral corticosteroids (inhaled or topical corticosteroids are permitted)
o cylcosporin
o alkylating agents
o other immunosuppressive agents
o rifampin
o phenytoin
o phenobarbitol
•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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
15/03/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 593 0
2010

Funding & Sponsors
Funding source category [1] 3131 0
University
Name [1] 3131 0
National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales (UNSW)
Country [1] 3131 0
Australia
Funding source category [2] 3132 0
Commercial sector/Industry
Name [2] 3132 0
Merck, Sharp and Dohme
Country [2] 3132 0
Australia
Primary sponsor type
University
Name
National Centre in HIV Epidemiology and Clinical Research
Address
Level 2
376 Victoria St
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 2815 0
None
Name [1] 2815 0
Address [1] 2815 0
Country [1] 2815 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5103 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 5103 0
St Vincent's Hospital,
Victoria Street
Darlinghurst NSW 2010
Ethics committee country [1] 5103 0
Australia
Date submitted for ethics approval [1] 5103 0
Approval date [1] 5103 0
17/12/2007
Ethics approval number [1] 5103 0
07/SVH/89

Summary
Brief summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28407 0
Address 28407 0
Country 28407 0
Phone 28407 0
Fax 28407 0
Email 28407 0
Contact person for public queries
Name 11564 0
Dr Christoph Boesecke
Address 11564 0
NCHECR Level 2
376 Victoria St
Darlinghurst NSW 2010
Country 11564 0
Australia
Phone 11564 0
02 9385 0900
Fax 11564 0
Email 11564 0
cboesecke@nchecr.unsw.edu.au
Contact person for scientific queries
Name 2492 0
Professor Anthony Kelleher
Address 2492 0
NCHECR Level 2
376 Victoria St
Darlinghurst NSW 2010
Country 2492 0
Australia
Phone 2492 0
02 9385 0900
Fax 2492 0
Email 2492 0
tkelleher@cfi.unsw.edu.au

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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