RAL-eve Study: Raltegravir Substitution Study

We enrolled virologically suppressed HIV-1 infected patients with injection site reactions for a switch from enfuvirtide to raltegravir. At baseline, enfuvirtide was switched to raltegravir without additional changes to the antiretroviral regimen allowed. Viral load, T-cells, and toxicity were evaluated at baseline, 2, 4, 12 and 24 weeks. Adherence and injection site reactions were evaluated at baseline, 4, 12 and 24 weeks. The single-copy assay was used to measure HIV RNA levels at screening, baseline and at 12 and 24 weeks.

Inclusion criteria

• HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry.
• ART for at least 6 months prior to study entry with a regimen that includes enfuvirtide.
• Self-defined infusion site reaction to enfuvirtide (usually will be painful inflammatory nodules)
• No change in ART regimen for at least 3 months prior to study entry.
• CD4+ cell count >50/mm3 at screening (obtained within 60 days prior to study entry).
• Documentation of HIV-1 RNA below the limit of quantification of an ultrasensitive assay
• All HIV-1 RNA levels obtained within 6 months prior to study entry are below the limits of quantification on all tests, except as explained above in section 4.1.6 for a single detectable viral load of <50 copies but <200 copies in last 6 months.
• Laboratory values obtained within 60 days prior to entry:

• Absolute neutrophil count (ANC) >750/mm3
• Hemoglobin >9.0 g/dL for female subjects and>10.0 g/dL for male subjects
• Platelet count >50,000/mm3
• Calculated creatinine clearance (CrCl) >30 mL/min, as estimated by the Cockcroft-Gault equation*
• AST (SGOT), ALT (SGPT), and alkaline phosphatase <5 x ULN
• Total bilirubin <2.5 x ULN. If the subject is taking an indinavir- or atazanavir-containing regimen at the time of screening, total bilirubin <5 x ULN is acceptable.
• For females of reproductive potential will need a negative serum or urine pregnancy test within 48 hours prior to entry.
• Men and women age >18 years.
• Ability and willingness of subject to provide informed consent.

Exclusion criteria

• 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.
• An opportunistic infection within 60 days prior to entry.
• Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation.
• Active drug or alcohol use or dependence that, in the opinion of the Protocol Director, would interfere with adherence to study requirements.
• Receipt of a non-HIV vaccination within 30 days prior to study entry or plan for receipt of vaccination during the study.
• Plan to change the background ART within 24 weeks after study entry.