Statin Adjunct Therapy Among ART-treated Adults in Sub-Saharan Africa: Atorvastatin and Rosuvastatin Equivalence Trial

Study Overview
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Brief Summary
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This study will determine whether 36 months of daily atorvastatin or rosuvastatin have equivalent effects in reduction of immune activation, inflammation and immune aging, when given as adjunct therapy among patients receiving antiretroviral therapy in an African cohort

Detailed Description
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This is a randomized, open-label trial

Official Title
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Statin Adjunct Therapy Among HAART-treated Adults in Sub-Saharan Africa: Equivalence of Atorvastatin and Rosuvastatin

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: ART, Atorvastatin
* Drug: ART, Rosuvastatin
* Drug: ART, No statin
* Drug: Healthy-HIV-negative


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-positive individuals 18 years and older, that have initiated three first-line drug highly active antiretroviral therapy within three months within the Infectious Diseases Institute HIV treatment cohort Individuals that provide written informed consent to participate in the clinical trial Exclusion Criteria: Individuals with dyslipidemia and eligible to receive or already receiving statin therapy Pregnant or lactating mothers Individuals with another active or controlled inflammatory condition Individuals with deranged liver function tests 3 fold and above

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ART-Atorvastatin adjunct therapy<br>ART, atorvastatin | Drug: ART, Atorvastatin<br>* ART, Atorvastatin<br>* Other names: Atovastatin adjunct therapy;|
| Experimental: ART-Rosuvastatin adjunct therapy<br>ART, rosuvastatin | Drug: ART, Rosuvastatin<br>* ART, Rosuvastatin<br>* Other names: Rosuvastatin adjunct therapy;|
| Experimental: ART-without statin adjunct therapy<br>ART, no statin | Drug: ART, No statin<br>* ART, No statin<br>* Other names: No statin adjunct therapy;|
| Experimental: Healthy-HIV-negative<br>Age-matched HIV-negative, healthy volunteers from the same community | Drug: Healthy-HIV-negative<br>* Age-matched, Healthy HIV-negative<br>* Other names: HIV-negative controls;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Similar rate of reduction of immune activation between atorvastatin and rosuvastatin arms (p<o.05) | measured by percentage of HLADR+CD38+T-cells | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Similar rate of change of immune aging markers, between ART-treated adults with and without statin (atorvastatin and rosuvastatin) adjunct therapy arms (P-value<0.05) | Measured by Percentage of CD4+ and CD8+ naive T-cells or percentage of expressing Ki67 T-cells or percentage of low CFSE+T-cells or increase in percentage of CD28-/CD57+ T-cells or percentage of individuals with low host responses to influenza vaccine among HIV-infected adults at ART initiation | 36 months | 
| Similar rate of reduction of inflammatory markers, between atorvastatin and rosuvastatin arms (p<0.05) | Measured by levels of IL6 in pg/ml, hsCRP in pg/ml, d-dimers in pg/ml, IFABP in pg/ml, and LPS in pg/ml | 36 months | 
| Biological pathways affected by atorvastatin and rosuvastatin | number of genes down-regulated by either atorvastatin or rosuvastatin | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adults, antiretroviral therapy