Raltegravir (Isentress/MK-0518) and HIV-1 Infected CD4 Cells During Acute/Early HIV-1

Study Overview
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Brief Summary
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This is an investigator-initiated, two-year, randomized, controlled, single-center, open-label, pilot study comparing 3-drug highly active antiretroviral therapy (HAART) to 3-drug HAART plus raltegravir for persons with acute and early HIV-1 infection. The study will test the hypothesis that use of the integrase inhibitor raltegravir (400 mg BID orally) to inhibit the integration step of the HIV-1 life cycle in conjunction with HAART in subjects with recently acquired HIV-1 infection will decrease the number of HIV-1 infected CD4+ T-cells to a greater extent than a 3-drug HAART regimen.

Detailed Description
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The study will be conducted at the UW Primary Infection Clinic and the UW AIDS Clinical Trials Unit. Secondary objectives will characterize safety, tolerability, plasma HIV-1 RNA and CD4+ T-cell values. The 3-drug HAART will be chosen and provided by the subject.

Official Title
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Impact of Raltegravir (Isentress/MK-0518) - Containing Regimens on HIV-1 Infected CD4+ T-Cells During Acute and Early HIV-1 Infection: A Randomized, Controlled Study Comparing Standard Antiretroviral Therapy to Standard Therapy Plus Raltegravir

Conditions
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Human Immunodeficiency Virus

Intervention / Treatment
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* Drug: 3-drug anti-HIV therapy
* Drug: Raltegravir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute or Early HIV-1 infection HIV-1 RNA > or equal to 500 copies/mL Acceptable safety lab results (specified in protocol) Negative pregnancy test for females Willingness to use contraception (for females of reproductive potential Exclusion Criteria: Prior receipt of investigational HIV-1 vaccine Use of immunomodulators other than systemic steroids within 30 days before entry Serious medical or psychiatric illness that would interfere with study participation Active drug or alcohol use that would interfere with study participation Allergy/hypersensitivity to raltegravir Pre- or Post-exposure prophylaxis for the exposure that led to HIV-1 acquisition Pregnancy or breastfeeding History of malignancy (other than localized squamous cell or basal cell cancer of the skin)

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Raltegravir + 3-drug anti-HIV therapy<br> | Drug: 3-drug anti-HIV therapy<br>* 3 FDA-approved drugs, including two nucleos(t)ide reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor (Low dose ritonavir can be used to enhance the protease inhibitor and is not considered one of the 3 anti-HIV drugs)<br>Drug: Raltegravir<br>* 400 mg BID PO<br>* Other names: Isentress;|
| Active Comparator: 3-drug anti-HIV therapy<br> | Drug: 3-drug anti-HIV therapy<br>* 3 FDA-approved drugs, including two nucleos(t)ide reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor (Low dose ritonavir can be used to enhance the protease inhibitor and is not considered one of the 3 anti-HIV drugs)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of HIV-1 infected CD4+ T-cells measured by a quantitative HIV-1 DNA PCR assay |  | 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4+ T-cells |  | 96 weeks | 
| Plasma HIV-1 RNA |  | 96 weeks | 
| Grade 3 and 4 signs and symptoms or laboratory toxicities at least one grade higher than baseline |  | From study drug start to 8 weeks after drug discontinuation | 
| Plasma HIV-1 RNA |  | Baseline to Week 8 | 
| Tolerability (Discontinuation of raltegravir) |  | 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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human immunodeficiency virus, raltegravir, primary HIV infection, HIV-1