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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: Tenofovir + emtricitabine + raltegravir.

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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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; RAL; FTC

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Kirby Institute
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Anthony Kelleher, MBBS (Hons) PhD, FRACP, FRCPA, Kirby Institute

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Peer reviewed publication of trial results

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: February 28, 2008
• First Submitted That Met QC Criteria: March 18, 2008
• First Posted (Estimate): March 24, 2008

Study Record Updates

• Last Update Posted (Actual): August 31, 2017
• Last Update Submitted That Met QC Criteria: August 30, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Viral compartments; integrase inhibitor therapy; viral species
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Tenofovir; Emtricitabine; Raltegravir Potassium
• Other Study ID Numbers: PINT01