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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: Tenofovir + emtricitabine + raltegravir.


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: antiretroviral therapy<br>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.<br>* TDF 300mg once daily + FTC 200mg once daily + RAL 400mg twice daily.<br>* Other names: RAL;|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Viral compartments, integrase inhibitor therapy, viral species