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

Kirby Institute

Status: Completed

Conditions: HIV Infection

Treatments: Drug: Tenofovir + emtricitabine + raltegravir.

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00641641

PINT01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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16 participants in 1 patient group

antiretroviral therapy

Experimental group

Description:

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

Treatment:

Drug: Tenofovir + emtricitabine + raltegravir.