HIV infection Immune activation
Conditions
Interventions
This is a double blind, randomized, placebo-controlled therapeutic intervention study with a cross-over design.
The patients will be assigned to random groups: One receives rosuvastatin 20 mg daily,
Sponsors
Stichting Research Interne Geneeskunde, OLVG, Amsterdam, the Netherlands
Eligibility
Inclusion criteria
Inclusion criteria: 1. Adults 18 years of age or older; 2. HIV-1 infection, as documented by a licensed ELISA test kit and confirmed by a Western blot assay; 3. 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; 4. Treatment naïve, i.e. no current of previous use of HAART; 5. 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; 6. Willingness to have blood drawn; 7. Non known allergy or contraindication to rosuvastatin use; 8. Ability to understand and willingness to sign the informed consent; 9. Willingness to have blood stored for future phenotyping and genotyping; 10. CD4 cell count greater than 350 cells/ml; 11. Two viral loads that average greater than 1000 copies/ml within a 4 week period; 12. 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; 13. 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; 14. Laboratory values: A. Absolute neutrophil count (ANC) greater than or equal to 1000/mm3; B. Hemoglobin greater than or equal to 7.5 mmol/L; C. Platelet count greater than or equal to 100,000/mm3; D. Creatinine less than or equal to 2 x ULN; E. Serum amylase and lipase less than or equal to 1.25 x ULN. 15. Negative serum pregnancy test at randomization.
Exclusion criteria
Exclusion criteria: 1. Pregnancy or breast feeding; 2. 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; 3. Serious illness requiring systemic treatment and/or hospitalization within 30 days of entry; 4. Evidence of active opportunistic infections or neoplasms that require chemotherapy during the study period; 5. Allergy or hypersensitivity to rosuvastatin or any of its components; 6. History of myositis or rhabdomyolysis with use of any statins; 7. History of inflammatory muscle disease such as poly- or dermatomyositis; 8. Concomitant use of fibric acid derivatives or other lipid lowering agents including statins and ezetimibe; 9. Concomitant use of drugs that have significant interactions with rosuvastatin; 10. Concomitant use of St. Johns wort; 11. Concomitant use of Valproic acid; 12. Patients who are on concurrent immunomodulatory agents; 13. Serum LDL cholesterol less than 1.0 mmol/L; 14. Vaccinations within 6 weeks of study entry.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Objective: To investigate the effect of rosuvastatin 20 mg qd on subsequent immune activation markers in treatment-naïve HIV-patients: Circulating LPS (LAL assay), TLR mRNA expression in whole blood, circulating IL-6, D-dimer, hsCRP, CD38 and HLA-DR expression on lymphocytes, and microparticles and endogenous thrombin potential as indicators of endothelial damage. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Objective: To investigate the effect of rosuvastatin 20 mg qd on HIV viral load, CD4 cell count, total cholesterol and cholesterol subfractions, ApoB/ApoA1 ratio, CK, liver enzymes, renal function, and complete blood count as well as on markers of quality of life measured with the EuroQol-6D questionnaire in treatment-naïve HIV-patients throughout the study period. | — |
Contacts
Public ContactW.L. Blok
OLVG, Internist
Outcome results
None listed