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

HIV Infection Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00641641
• Other study ID #: PINT01
• Status: Completed
• Phase: N/A
• First received: February 28, 2008
• Last updated: August 30, 2017
• Start date: March 2008
• Est. completion date: June 2011

Study information

• Verified date: August 2017
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infection
• HIV Infections
• Infection

Intervention

Drug:
• Tenofovir + emtricitabine + raltegravir.
TDF 300mg once daily + FTC 200mg once daily + RAL 400mg twice daily.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Kirby Institute	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Australia, 

References & Publications (2)

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 charact — View 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 afterwa — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.

External Links

•   Peer reviewed publication of trial results