Evaluating the Effect of CHanging EnfuvirtidE to Raltegravir in HIV Infected Subjects

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is: To assess the virologic effect of changing enfuvirtide to MK-0518(raltegravir) in human immunodeficiency virus type 1(HIV-1) infected patients who have an undetectable level of serum human immunodeficiency virus(HIV) (< 75 copies/ml by branch deoxyribonucleic acid (bDNA) assay, < 50 copies/ml by Ultrasensitive Polymerase Chain Reaction(PCR) assay) on their current HIV medication regimen. Hypothesis: HIV-1 infected individuals well controlled on an enfuvirtide containing regimen with HIV RNA levels below limits of quantification can safely have the investigational integrase inhibitor, MK-0518 substituted for enfuvirtide without loss of virologic suppression.

Detailed Description
-----------------
Human immunodeficiency virus type 1(HIV-1) infected patients who have had an undetectable viral load on an enfuvirtide containing regimen at the Kaiser Permanente Hayward, Los Angeles, San Francisco, and Santa Clara Medical Centers will be enrolled. Patients will receive open label MK-0518 (raltegravir) 400mg orally twice a day as substitution for enfuvirtide for 24 weeks.

Official Title
-----------------
Virologic Outcomes of Changing Enfuvirtide to Raltegravir in HIV-1 Patients Well Controlled on an Enfuvirtide Based Regimen

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Drug: raltegravir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must meet all of the following inclusion criteria to be eligible for participation in this study. Subject is ≥ 18 years of age and able to understand and willing to sign a written informed consent form, which must be obtained prior to initiation of the study. Documented laboratory diagnosis of HIV-1 infection (positive Enzyme-linked immunosorbent assay (ELISA) HIV-1 antibody test confirmed by western blot, p24 assay, HIV-1 RNA, or culture). Have documented plasma HIV-1 RNA level(s) of < 75 copies/ml by branched deoxyribonucleic acid(bDNA) assay, or < 50 copies/ml by Ultrasensitive Polymerase Chain Reaction(PCR) for at least 6 months prior to screening visit. Currently receiving a stable antiretroviral regimen consisting of enfuvirtide plus at least 2 other antiretrovirals for at least 6 months. Negative serum pregnancy test (females of childbearing potential only) and are willing to use an adequate method of contraception throughout the duration of the study. Exclusion Criteria: Patients who meet any of the following exclusion criteria are not to be enrolled in this study. Any prior therapy with MK-0518 or any other HIV-1 integrase inhibitor. Any HIV-1 viral load > 75 copies/ml by bDNA assay, or > 50 copies/ml by Ultrasensitive PCR assay in the 6 months prior to screening visit (A single blip of HIV-1 viral load >75 copies but <400 copies by bDNA assay, or >50 copies but <400 copies by Ultrasensitive PCR assay in the six months prior to screening visit with at least one subsequent HIV-1 viral load below the limit of detection will be accepted.) Any previous known hypersensitivity to components of the study drug formulation. Weight < 40 kilograms. Patient requires or is anticipated to require any of the prohibited medications noted in the protocol. Acute therapy for serious illness (in the opinion of the investigator) within 14 days prior to study entry unless the subject has completed ≥ 7 days of therapy and is considered clinically stable by the investigator. Any condition which, in the opinion of the investigator, would compromise the subject's ability to participate in the study. Any active opportunistic infections or Centers for Disease Control and Prevention (CDC) Category C conditions (with the exception of stable cutaneous Kaposi's Sarcoma and wasting syndrome due to HIV infection). Any malignancy requiring chemotherapy. Subject has any of the following laboratory results at screening: Hemoglobin < 8.0 gr/dl Absolute neutrophil count < 750 cells/ml Platelet count < 40,000 Creatinine > 2.0 or calculated creatinine clearance < 40 ml/min Female patient who is pregnant or breast-feeding, or expecting to conceive or donate eggs during the study. Male patient who is planning to impregnate or provide sperm donation during the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-0518 (raltegravir)<br>Open label, single arm. All patients to receive MK-0518 400mg orally twice a day for 24 weeks, as substitution for enfuvirtide. | Drug: raltegravir<br>* This is a single-arm, open-label, non-randomized pilot study in human immunodeficiency virus type 1 (HIV-1) positive patients who have an undetectable viral load on their current enfuvirtide containing medication regimen. The treatment regimen will consist of replacing enfuvirtide with MK-0518 400 mg twice a day given as part of the patient's HIV medication regimen. The study regimen will be administered for 24 weeks, with patients given the option of continuing on the study medication past that time if they wish to. Patients serve as their own control as they have viral control (HIV ribonucleic acid (RNA) below limits of quantification) for at least 6 months with enfuvirtide prior to switch to raltegravir.<br>* Other names: MK-0518, Isentress;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Undetectable Human Immunodeficiency Virus (HIV) Viral Load at Week 24. | To assess the virologic effect of changing enfuvirtide to MK-0518 (raltegravir) in human immunodeficiency virus type 1 (HIV-1) infected patients who have an undetectable level of serum HIV (undetectable level of serum HIV defined as < 75 copies/ml by bDNA assay or < 50 copies/ml by Ultrasensitive PCR assay) on their current HIV medication regimen. | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Change in Cluster of Differentiation 4(CD4) Cell Count From Baseline at Week 24 | To study the immunologic effect of changing enfuvirtide to MK-0518 (raltegravir) in HIV-1 infected patients who have an undetectable level of serum HIV (undetectable serum HIV defined as < 75 copies/ml by bDNA assay or < 50 copies/ml by Ultrasensitive PCR assay)on their current HIV medication regimen. | 24 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Treatment Experience, On enfuvirtide