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

• ClinicalTrials.gov Identifier: NCT00641641
• Recruitment Status: Completed
• First Posted: March 24, 2008
• Results First Posted: May 27, 2013
• Last Update Posted: August 31, 2017
• Sponsor: Kirby Institute
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Sally Hough, Kirby Institute

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.

Condition or disease	Intervention/treatment	Phase
HIV Infection	Drug: Tenofovir + emtricitabine + raltegravir.	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: March 2008
• Actual Primary Completion Date: March 2011
• Actual Study Completion Date: June 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: antiretroviral therapy; tenofovir (TDF) + emtricitabine (FTC) as a fixed dose combination administered orally once per day and raltegravir (RAL) administered orally twice per day.	Drug: Tenofovir + emtricitabine + raltegravir.; TDF 300mg once daily + FTC 200mg once daily + RAL 400mg twice daily.; Other Names: TDF; FTC; RAL

Outcome Measures

Primary Outcome Measures :

1. Mean Change From Baseline Plasma HIV RNA (Log Copies/mL) [ Time Frame: 12 times within 48 weeks. ]
   change was calculated as the mean of 12 assessments minus the baseline value

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Kirby Institute

Merck Sharp & Dohme Corp.

Investigators

• Principal Investigator: Anthony Kelleher, MBBS (Hons) PhD, FRACP, FRCPA; Kirby Institute

More Information

Additional Information:

Peer reviewed publication of trial results 

Publications of Results:

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Sally Hough, Senior Clinical Project Coordinator, Kirby Institute
• ClinicalTrials.gov Identifier: NCT00641641 History of Changes
• Other Study ID Numbers: PINT01
• First Posted: March 24, 2008
• Results First Posted: May 27, 2013
• Last Update Posted: August 31, 2017
• Last Verified: August 2017

Keywords provided by Sally Hough, Kirby Institute:

Viral compartments; integrase inhibitor therapy; viral species

Additional relevant MeSH terms:

Infection; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; Tenofovir; Raltegravir Potassium; Emtricitabine; Antiviral Agents; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Retroviral Agents; Anti-HIV Agents; HIV Integrase Inhibitors; Integrase Inhibitors