Clinical trial NCT00887653: Changes in Lipids and Safety of Raltegravir in HIV+ Patients With Hyperlipidemia While on Current Standard Therapy
Official title: Changes in Lipid Profiles and Safety of Raltegravir Based Antiretroviral Therapy in HIV-1-infected Patients With Hyperlipidemia While on Current Standard Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
Hyperlipidemia
Hypertriglyceridemia
HIV Infections
Lead sponsor: The Miriam Hospital
Sponsor class: OTHER
Collaborators: name: Tufts Medical Center
name: Merck Sharp & Dohme LLC
First posted: 2009-04-24
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The success of combination antiretroviral therapy heralded a revolution in the treatment of HIV in the mid-1990s. However, severe treatment-associated side effects have been observed including diabetes and increased cholesterol which are linked to premature heart attacks. This effect has been described among many regimens containing protease inhibitors (PIs), as well as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Raltegravir is a new medicine which has been shown to be potent and efficacious in suppression of the HIV. This study hopes to determine if switching from a PI or NNRTI to raltegravir will decrease cholesterol in subjects with high cholesterol and well controlled HIV. In addition, the study aims to confirm that raltegravir is safe and well tolerated. It also seeks to confirm if raltegravir will have similar anti-HIV activity compared with the patient's previous regimen.

The study will last 6 months and will involve 20 subjects. HIV-1 infected men and women on PIs or NNRTIs for at least 12 months before study entry with well controlled HIV will be recruited.

Hypotheses:

1. Patients with elevated lipid levels while on combination antiretroviral therapy with PIs or NNRTIs will experience an improvement in lipid levels after switching their PI or NNRTI to a raltegravir based regimen.
2. Raltegravir will be safe and well tolerated.
3. Raltegravir will have similar antiretroviral activity compared with the prior regimen.

Primary Objective:

To demonstrate an improvement in lipid profile (triglycerides or LDL) in subjects switched to raltegravir from PIs or NNRTIs at 2, 3, and 6 months after study entry.

Study Design: Subjects will be given the option to switch from their current regimen to raltegravir at 400mg twice daily. Those who consent, will receive raltegravir provided by the study for 6 months. At entry, the subjects will undergo a complete physical exam and thereafter targeted exams at each visit. Labs will be drawn as part of clinical care at 2, 3, and 6 months. Some of the blood will be stored for later analysis. Also, the subjects will answer regular surveys on drug toxicity and quality of life. Their cholesterol level will be compared before and after the study. At the end of the study, the participants may choose to continue on raltegravir if they desire.

Detailed description: The success of combination antiretroviral therapy heralded a revolution in the management of patients with HIV in the mid-1990s. Increasingly, severe treatment-associated metabolic side effects have been observed and linked to premature coronary artery disease. This effect has been described among many regimens containing protease inhibitors (PIs) as well as non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Raltegravir is a novel HIV-1 integrase inhibitor which in a comparison study with efavirenz has been shown to be potent and efficacious in suppression of the HIV-1. Minimal side effects were reported which mainly included nausea, headache, dizziness, diarrhea, and insomnia.

Hypotheses:

1. Patients with elevated lipid levels while on combination antiretroviral therapy with PIs or NNRTIs will experience an improvement in lipid levels after switching their PI or NNRTI to a raltegravir based regimen.
2. Raltegravir will be safe and well tolerated.
3. Raltegravir will have similar antiretroviral activity compared with the prior regimen.

Primary Objective:

To demonstrate an improvement in triglycerides or LDL in subjects switched to raltegravir from PIs or NNRTIs at 2 months, 3 months, and 6 months after study entry.

Secondary Objectives:

To assess the immunologic and virologic outcomes in subjects switched to raltegravir from PIs or NNRTIs at 2, 3, and 6 months after entry.

Study Design:

This will be a single arm study where subjects will be given the option to switch from their current regimen to raltegravir at 400mg twice daily.

Primary endpoint: Change from baseline LDL and change from baseline triglycerides at 3 months, adjusted for BMI and smoking status.

The subjects' plasma viral load before and after switching will be compared with a paired t test at each time point.

The subjects' CD4+ T cell count will be compared with a paired t test before and after switching.

Eligibility criteria: Inclusion Criteria:

* Age \>18
* Fasting LDL\>130 mg/dL
* Fasting triglycerides \>250 mg/dL
* Plasma viral load below 50 copies/mL on current regimen for 6 months prior to study entry.
* No prior history of any NRTI resistance.

Exclusion Criteria:

* History of NRTI resistance mutations
* Need for medications that have drug interactions with raltegravir: dilantin, phenobarbitol and rifampin
* Unstable clinical condition, such as unstable cardiac disease, or cancer requiring ongoing chemotherapy or radiation therapy, or other medical condition which, in the opinion of the investigator, would preclude a subject from safely undergoing study procedures.
* Breast-feeding or pregnancy.
* Use of immunosuppressive medications within 60 days prior to study entry.
* Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

Primary outcomes:
measure: Change From Baseline Triglycerides
timeFrame: 3 months
measure: Change From Baseline Triglycerides
timeFrame: 6 months
Secondary outcomes:
measure: Proportion of Patients With Plasma Viral Load Below the Limit of Detection
timeFrame: 6 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts University
state: Massachusetts
city: Providence
country: United States
facility: Miriam Hospital Immunology Clinic
state: Rhode Island
Study officials:
affiliation: The Miriam Hospital
name: Karen Tashima, MD
role: PRINCIPAL_INVESTIGATOR
References: