Atorvastatin for HAART Suboptimal Responders

Study Overview
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Brief Summary
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We hypothesise that atorvastatin changes immune activation among HAART-treated adults with suboptimal cluster cell differentiation 4 (CD4) recovery by 25%

Detailed Description
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The investigators have previously shown that up to 40% of HAART-treated adults have suboptimal CD4 recovery despite viral suppression. The investigators have also shown that immune activation and exhaustion are significantly higher among patients that do not exhibit satisfactory rise in CD4 counts despite viral suppression (suboptimal responders); when compared with their counterparts with viral suppression and satifactory CD4 count recovery (optimal responders). Given that atorvastatin changes immune activation in this pilot study, then larger studies can be done to understand its effect on CD4 count increase among suboptimal responders.

Official Title
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Use of Atorvastatin as Adjuvant Therapy Among Suboptimal Responders to Antiretroviral Therapy in an African Cohort of HAART-treated Adults: A Randomised Controlled Trial

Conditions
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Acquired Immune Deficiency Syndrome Virus

Intervention / Treatment
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* Other: atorvastatin, Lipitor®
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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List of inclusion Criteria: HIV-infected adults on antiretroviral therapy for at least 6 years with sustained viral suppression (viral load<400 copies), and CD4 increase below 300 cells (difference between current and baseline CD4 count). List of exclusion Criteria: History of an opportunistic infection within the previous six months, Pregnancy, History of myositis, History of ingestion of lipid-lowering agents at the baseline visit, Use of therapeutic agents known to have substantial drug-drug interactions with statins, and individuals on PI-containing HAART

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: atorvastatin, Lipitor®<br>Intervention is be atorvastatin, Lipitor® (40mg) 2 tablets daily (as adjuvant to HAART) for 12 weeks. Peripheral blood mononuclear cells (PBMC) will be collected for immune activation assays using flowcytometry | Other: atorvastatin, Lipitor®<br>* PBMC collected for immune activation assays using flowcytometry<br>* Other names: Lipitor®;Drug: Placebo<br>* PBMC collected for immune activation assays using flowcytometry<br>* Other names: atorvastatin placebo;|
| Placebo Comparator: Placebo<br>Intervention for the placebo comparator arm is Placebo 2 tablets daily for 12 weeks PBMC will be collected for immune activation assays using flowcytometry | Other: atorvastatin, Lipitor®<br>* PBMC collected for immune activation assays using flowcytometry<br>* Other names: Lipitor®;Drug: Placebo<br>* PBMC collected for immune activation assays using flowcytometry<br>* Other names: atorvastatin placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Immune Activation Levels After 12 Weeks of Atorvastatin 80mg Daily | Immune activation was measured by co-expression of CD38 and HLADR on CD4 T-cells (CD4+CD38+HLADR+) Mean percentage change at 12 weeks was calculated | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune activation, antiretroviral therapy, atorvastatin, immune exhaustion, adults, Africa