The Effect of Rosuvastatin on Immune Activation Markers in Treatment-naïve HIV-Positive Patients; a Randomized Placebo-Controlled Trial

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 30

Inclusion Criteria

• Adults 18 years of age or older.
• HIV-1 infection, as documented by a licensed ELISA test kit and confirmed by a Western blot assay
• No evidence of acute HIV infection. For the purposes of this study acute HIV infection will be defined as presence of a detectable HIV-1 viral RNA in the presence of a non reactive HIV-1 or HIV-2 antibody assay or an indeterminate western blot.
• Treatment naïve, i.e. no current of previous use of HAART
• Willingness to use a method of contraception during the study period. Adequate methods of birth control include: condoms, male or female, with or without a spermicide; diaphragm or cervical cap with spermicide; intrauterine device; any of the methods that require a prescription (such as contraceptive pills or patch, Norplant, Depo-Provera, and others) or a male partner who has previously undergone a vasectomy.
• Willingness to have blood drawn.
• Non known allergy or contraindication to rosuvastatin use.
• Ability to understand and willingness to sign the informed consent.
• Willingness to have blood stored for future phenotyping and genotyping.
• CD4 cell count greater than 350 cells/ml.
• Two viral loads that average greater than 1000 copies/ml within a 4 week period.
• Liver function tests (AST or ALT) not greater than 1.5 times the upper limit of normal. Evidence of active hepatitis B or C will not be considered an exclusion criterion if the liver function tests are within normal limits.
• Creatine phosphokinase elevations (CK) not greater than 3 times the upper limit of normal (ULN) on two sequential determinations and, in the opinion of the investigator, without clear association with exercise.
• Laboratory values:
Absolute neutrophil count (ANC) greater than or equal to 1000/mm3.
Hemoglobin greater than or equal to 7.5 mmol/L
Platelet count greater than or equal to 100,000/mm3
Creatinine less than or equal to 2 x ULN.
Serum amylase and lipase less than or equal to 1.25 x ULN.
• Negative serum pregnancy test at randomization.

Exclusion Criteria

• Pregnancy or breast feeding.
• Active drug use or alcohol abuse/dependence, which in the opinion of the investigators will interfere with the patient's ability to participate in the study.
• Serious illness requiring systemic treatment and/or hospitalization within 30 days of entry.
• Evidence of active opportunistic infections or neoplasms that require chemotherapy during the study period
• Allergy or hypersensitivity to rosuvastatin or any of its components.
• History of myositis or rhabdomyolysis with use of any statins.
• History of inflammatory muscle disease such as poly- or dermatomyositis.
• Concomitant use of fibric acid derivatives or other lipid lowering agents including statins and ezetimibe.
• Concomitant use of drugs that have significant interactions with rosuvastatin. .
• Concomitant use of St.Johns wort.
• Concomitant use of Valproic acid.
• Patients who are on concurrent immunomodulatory agents
• Serum LDL cholesterol less than 1.0 mmol/L.
• Vaccinations within 6 weeks of study entry.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>circulating LPS (LAL assay), TLR mRNA expression in whole blood, circulating<br /><br>IL-6, D-dimer, hsCRP, CD38 and HLA-DR expression on lymphocytes, and<br /><br>microparticles and endogenous thrombin potential as indicators of endothelial<br /><br>damage.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>HIV viral load, CD4 cell count, total cholesterol and cholesterol subfractions,<br /><br>ApoB/ApoA1 ratio, CK, liver enzymes, renal function, and complete blood count<br /><br>as well as on markers of quality of life measured with the EuroQol-6D<br /><br>questionnaire in treatment-naïve HIV-patients throughout the study period.</p><br>