Changes in Lipids and Safety of Raltegravir in HIV+ Patients With Hyperlipidemia While on Current Standard Therapy

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:

• 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.
• Raltegravir will be safe and well tolerated.
• 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.

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.