Rosuvastatin to Decrease Residual Immune Activation in HIV Infection

Methodology Phase II pilot study; open-label; non comparative, bicentric, on-off design

Estimated enrolment 40 subjects

Outcomes Primary outcome :

• Variation at month 3 in the proportion of CD8 T lymphocytes co-expressing CD38 and HLA-DR

Secondary outcomes :

• Evolution of plasma/serum levels of CRP-HS, IL-6, soluble CD14 between baseline and month 3 and between month 3 and month 6
• Evolution of markers of CD4 T-cell activation (HLA-DR, Ki67) and CD8 T-cell activation (CD38, HLA-DR, Ki67) between baseline and month 3 and between month 3 and month 6 and evolution of the CD4/CD8 ratio between baseline and month 3 and between month 3 and month 6
• Evolution of CD4 T-cell count between baseline and month 3
• Evolution of HDL and LDL cholesterol between baseline and month 3 and between month 3 and month 6
• Relationship between HDL cholesterol and CD4/CD8 ratio at baseline, month 3 and month 6
• Relationship between the levels of T-cell activation and of plasma HIV-RNA levels at a detection level of 3 copies/mL
• Adverse events grade > 2 Eligibility Inclusion criteria
• HIV-infected patients receiving a combination of antiretroviral therapy for at least 24 months, unchanged since at least 18 months, exhibiting plasma HIV-RNA level below 20 copies and circulating CD4 T cell count below 500/mm3
• No indication for a treatment with statins (LDL cholesterol < 4.1 mmol/L under stable diet).

Non-inclusion criteria

• Patients receiving Maraviroc
• Patients receiving immune suppressing drugs
• Ongoing opportunistic, bacterial or viral infection
• CRP ≥ 10 mg/mL
• Co-infection with HCV (except if HCV cure), chronic HBV infection with active replication of HBV
• Indication for a treatment with statins
• Pregnancy
• CPK > 3x Normal values
• ALT or AST > 2x Normal values
• TG > 4 mmol/L
• DFG < 60 mL /min/1.73 m2
• Personal or familial history of genetic muscular disease
• History of muscular or hepatic toxicity with a statin or a fibrate
• Liver disease (TP < 70%).
• Hypothyroidism
• Concomitant treatment with : Kétoconazole, Itraconazole, Ciclosporine, Erythromycine, Cimétidine, Quinidine, Diltiazem, Vérapamil, systemic corticosteroids, Phénobarbital, Phénytoïne, Carbamazépine, Rifampicine, Lansoprazole
• Vaccination during the study

Intervention Rosuvastatin (20 mg/d per os) Intervention duration: 3 months Follow-up for 3 additional months

Statistical methods Bilateral Two-sided paired Wilcoxon to analyze the variation in the proportion of CD8 T lymphocytes that co-express CD38 and HLA-DR at month 3 (primary outcome).

The evolution of parameters of interest between 2 visits will also be analyzed using bilateral two-sided paired Wilcoxon test. Statistical significance will be considered for p< 0.05.

Substudies

Estimated planning or Study / Trial timetable Trial/study start date: April 2012 Enrolment period: 12 months Subject participation duration: 6 months Total trial/study duration: 18 months Estimated study/trial completion date: October 2013 [default date: date of last follow-up of last included patient, else justify the chosen date: date of "gel de la base de données", date of end of substudies analyses (think to delay for sampling transport, duration of technical analyses)]

Study / Trial design Phase II open-label pilot bicentric non comparative study. Patients eligible will receive Rosuvastatin for 3 months while continuing antiretroviral therapy. Patients will be followed-up 3 additional months after stopping the study drug (on-off design)