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The Effect of Raltegravir on HIV Decay During Primary and Chronic Infection (PINT)

Primary Purpose

HIV Infection

Status

Completed

Phase

Not Applicable

Locations

Australia

Study Type

Interventional

Intervention

Tenofovir + emtricitabine + raltegravir.

About this trial

This is an interventional treatment trial for HIV Infection focused on measuring Viral compartments, integrase inhibitor therapy, viral species

Eligibility Criteria

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

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.

Sites / Locations

St Vincent's Hospital
407 Doctors
Holdsworth House Medical Practice
Taylor Square Private Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

antiretroviral therapy

Arm Description

tenofovir (TDF) + emtricitabine (FTC) as a fixed dose combination administered orally once per day and raltegravir (RAL) administered orally twice per day.

Outcomes

Primary Outcome Measures

Mean Change From Baseline Plasma HIV RNA (Log Copies/mL)

change was calculated as the mean of 12 assessments minus the baseline value

Secondary Outcome Measures

Full Information

NCT ID

NCT00641641

First Posted

February 28, 2008

Last Updated

August 30, 2017

Sponsor

Kirby Institute

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT00641641

Brief Title

The Effect of Raltegravir on HIV Decay During Primary and Chronic Infection

Acronym

PINT

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Completed

Study Start Date

March 2008 (undefined)

Primary Completion Date

March 2011 (Actual)

Study Completion Date

June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Kirby Institute

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infection

Keywords

Viral compartments, integrase inhibitor therapy, viral species

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

antiretroviral therapy

Arm Type

Experimental

Arm Description

tenofovir (TDF) + emtricitabine (FTC) as a fixed dose combination administered orally once per day and raltegravir (RAL) administered orally twice per day.

Intervention Type

Drug

Intervention Name(s)

Tenofovir + emtricitabine + raltegravir.

Other Intervention Name(s)

TDF, FTC, RAL

Intervention Description

TDF 300mg once daily + FTC 200mg once daily + RAL 400mg twice daily.

Primary Outcome Measure Information:

Title

Mean Change From Baseline Plasma HIV RNA (Log Copies/mL)

Description

change was calculated as the mean of 12 assessments minus the baseline value

Time Frame

12 times within 48 weeks.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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

Organizational Affiliation

Kirby Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

St Vincent's Hospital

City

Darlinghurst, Sydney

State/Province

New South Wales

ZIP/Postal Code

2010

Country

Australia

Facility Name

407 Doctors

City

Sydney

State/Province

New South Wales

ZIP/Postal Code

2010

Country

Australia

Facility Name

Holdsworth House Medical Practice

City

Sydney

State/Province

New South Wales

ZIP/Postal Code

2010

Country

Australia

Facility Name

Taylor Square Private Clinic

City

Sydney

State/Province

New South Wales

ZIP/Postal Code

2010

Country

Australia

12. IPD Sharing Statement

Citations:

PubMed Identifier

21860347

Citation

Koelsch KK, Boesecke C, McBride K, Gelgor L, Fahey P, Natarajan V, Baker D, Bloch M, Murray JM, Zaunders J, Emery S, Cooper DA, Kelleher AD; PINT study team. Impact of treatment with raltegravir during primary or chronic HIV infection on RNA decay characteristics and the HIV viral reservoir. AIDS. 2011 Nov 13;25(17):2069-78. doi: 10.1097/QAD.0b013e32834b9658. Erratum In: AIDS. 2012 Jul 17;26(11):1455. AIDS. 2012 Nov 28;26(18):2425.

Results Reference

result

PubMed Identifier

22410637

Citation

Murray JM, McBride K, Boesecke C, Bailey M, Amin J, Suzuki K, Baker D, Zaunders JJ, Emery S, Cooper DA, Koelsch KK, Kelleher AD; PINT STUDY TEAM. Integrated HIV DNA accumulates prior to treatment while episomal HIV DNA records ongoing transmission afterwards. AIDS. 2012 Mar 13;26(5):543-50. doi: 10.1097/QAD.0b013e328350fb3c.

Results Reference

result

PubMed Identifier

25730509

Citation

Hey-Cunningham WJ, Murray JM, Natarajan V, Amin J, Moore CL, Emery S, Cooper DA, Zaunders J, Kelleher AD, Koelsch KK; PINT study team. Early antiretroviral therapy with raltegravir generates sustained reductions in HIV reservoirs but not lower T-cell activation levels. AIDS. 2015 May 15;29(8):911-9. doi: 10.1097/QAD.0000000000000625.

Results Reference

derived

Links:

URL

http://www.ncbi.nlm.nih.gov/pubmed/21860347

Description

Peer reviewed publication of trial results

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The Effect of Raltegravir on HIV Decay During Primary and Chronic Infection

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