Atorvastatin on Biomarkers of Inflammation, Coagulopathy,... | NCT01351025

ID	Type	Description	Link
1U01AI068636	U.S. NIH Grant/Contract		View source

Name	Class
National Institute of Allergy and Infectious Diseases (NIAID)	NIH
Pfizer	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A: atorvastatin / placebo	Experimental	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period.	Drug: atorvastatin Drug: placebo for atorvastin
Arm B: placebo / atorvastatin	Experimental	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated placebo for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the dose of placebo was doubled at the week 4 visit. At week 20, the placebo was stopped for a 4-week washout period. At week 24, atorvastatin was started at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at week 28. At week 44, atorvastatin was stopped to allow for another 4-week washout period.	Drug: atorvastatin Drug: placebo for atorvastin

Interventions

Name	Type	Description	Arm Group Labels	Other Names
atorvastatin	Drug	10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4- week 20	Arm A: atorvastatin / placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in log10 IL-6	IL-6 (Interleukin 6) in log10 pg/mL: Difference between [change from week 24 to week 44] and [change from baseline to week 20] (i.e. [week 44 - week 24] - [week 20 - baseline])	baseline, week 20, week 24, and week 44
Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in CD4+ T-cell Activation Percent	CD4+ T-cell activation percent (% CD38+/DR+ of CD4+): Difference between [change from week 24 to week 44] and [change from baseline to week 20] (i.e. [week 44 - week 24] - [week 20 - baseline])	baseline, week 20, week 24, and week 44
Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in log10 D-dimer	D-dimer in log10 ng/mL: Difference between [change from week 24 to week 44] and [change from baseline to week 20] (i.e. [week 44 - week 24] - [week 20 - baseline])	baseline, week 20, week 24, and week 44
Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in CD8+ T-cell Activation Percent	CD8+ T-cell activation percent (% CD38+/DR+ of CD8+): Difference between [change from week 24 to week 44] and [change from baseline to week 20] (i.e. [week 44 - week 24] - [week 20 - baseline])	baseline, week 20, week 24, and week 44

Secondary Outcomes

Measure	Description	Time Frame
Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in MCP-1 (log10 Transformed)	Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

HIV-1 infected
Combination ART that includes any boosted PI regimen for at least 6 months prior to study entry
No plans to change the antiretroviral regimen in the next year
Must have been on the same HAART regimen for at least 12 weeks with no change prior to study entry. More information on this criterion can be found in the study protocol.
If on vitamin D replacement therapy, must have been on stable regimen for ≥ 1 mo. prior to study entry.
CD4+ T-cell count obtained within 45 days prior to study entry at any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
Screening HIV-1 RNA < 40 copies/mL by Abbott RealTime PCR at a laboratory certified by the DAIDS Virology Quality Assurance (VQA) program within 45 days prior to study entry.
All known HIV-1 RNA levels obtained within 180 days prior to study entry are below the limits of quantification on all tests, with documentation of at least 1 test by any FDA-approved assay at a CLIA-certified laboratory obtained between 90 to 180 days prior to study entry. A single RNA "blip" of < 500 copies/mL during this time period was permissible if RNA levels immediately before and after were below the limits of quantification for the assay.
Laboratory values obtained within 45 days prior to study entry- Absolute neutrophil count (ANC) 750/mm3, Hemoglobin ≥ 9.0 g/dL for female subjects,10.0 g/dL for male subjects, Platelet count ≥ 100,000/mm3, Calculated creatinine clearance (CrCl) 30 mL/min, as estimated by the Cockcroft-Gault equation, Creatine kinase (CK) < 3 x ULN, AST ≤ 2.0 x ULN, ALT ≤ 2.0 x ULN, Total bilirubin ≤ 2.5 x ULN. If the subject was taking an indinavir- or atazanavir-containing regimen at the time of screening, a total bilirubin of ≤ 5 x ULN is acceptable, Fasting LDL cholesterol ≥ 70 mg/dL and < 130 mg/dL, Fasting triglycerides < 400 mg/dL, Fasting glucose < 110 mg/dL
Screening plasma D-dimer > 0.34 μg/mL from a sample obtained within 45 days prior to study entry was the original D-dimer criterion. It was revised to ≥ 0.25 ug/mL four months after the first enrollment, and subsequently the D-dimer eligibility criterion was completely cut off a year later.
For females of reproductive potential (women who had not been post-menopausal for at least 24 consecutive months, i.e., who had menses within 24 months prior to study entry), or women who had not undergone surgical sterilization, specifically hysterectomy or bilateral oophorectomy or tubal ligation) required a negative serum or urine pregnancy test within 48 hours prior to entry. More information on this criterion can be found in the study protocol.
Must agree not to participate in the conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the subject/partner must use at least 2 reliable methods of contraception, (condoms, without a spermicidal agent; a diaphragm or cervical cap without spermicide; an IUD; or hormone-based contraceptive), for 2 weeks before study treatment, while receiving study treatment, and for 6 weeks after receiving study treatment. As hormone-based contraceptives (oral, transdermal, or subdermal) can affect coagulopathy biomarkers, subjects who plan on using such a contraceptive during the study must be taking the same product for ≥ 4 weeks prior to screening and be encouraged to continue throughout the duration of the study if medically feasible.
Karnofsky performance score ≥ 70 on at least one occasion within 45 days prior to study entry
Confirmation of the availability of the stored pre-entry fasting plasma, serum, and cell samples. The site had to confirm that these samples had entered into the Laboratory Data Management System (LDMS).

Exclusion Criteria:

Current or past malignancy (except non-melanoma cancer of the skin)
Coronary artery disease (CAD) or CAD equivalent including diabetes mellitus or National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) calculated 10-year coronary heart disease (CHD) risk of > 20%.
Known cirrhosis.
Known chronic active hepatitis B or C.
Thyroid-stimulating hormone (TSH) < 1.0 x lower limit of normal or > 1.0 x ULN.
Known inflammatory conditions, such as, but not limited to, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sarcoidosis, inflammatory bowel disease (IBD), chronic pancreatitis, autoimmune hepatitis, myositis, or myopathy.
Pregnant or breast-feeding.
Previous intolerance to any statin or any of its components.
Use of any lipid-lowering therapies including all statin drugs, Omega 3 fatty acids/fish oil, red yeast rice, and niacin products ≥ 1 g/day (e.g., niacin, nicotinic acid, vitamin B3) taken within 45 days prior to study entry. More information on this criterion can be found in the study protocol.
Immunosuppressant use, such as, but not limited to, systemic or potentially systemic glucocorticoids (including nasal or inhaled steroids), azathioprine, tacrolimus, mycophenolate, sirolimus, rapamycin, or cyclosporine within 45 days prior to study entry.
Use of any systemic antineoplastic or immunomodulatory treatment, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry. More information on this criterion can be found in the study protocol.
Concurrent use of prohibited medications. More information on this criterion can be found in the study protocol.
Heavy alcohol use as defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) (http://pubs.niaaa.nih.gov/publications/Practitioner/pocketguide/pocket\_guide3.htm) and alcohol or drug use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Current use of anticoagulation therapy other than ≤ 325 mg of daily aspirin.
Known coagulopathy, deep venous thrombosis, pulmonary embolism within 6 months prior to study entry.
Known active or recent (not fully resolved within 4 weeks prior to study entry) bacterial, fungal, parasitic, or viral infections.
Known history of recurrent rectal and/or genital herpes simplex virus (HSV) or varicella zoster virus (VZV) infection within 12 weeks prior to study entry.
Serious illness or trauma requiring systemic treatment and/or hospitalization within 4 weeks prior to study entry.
History of stroke.

Name	Affiliation	Role
Judith A. Aberg, M.D.	NYU/Bellevue/HIV/AIDS CTU	Study Chair
Daniel E Nixon, D.O., Ph.D.	Virginia Commonwealth University Medical Center	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
31788 Alabama CRS		Birmingham	Alabama	35294	United States
UCLA CARE Center CRS (601)

PubMed Identifier	Type	Citation	Retractions
36549898	Derived	Rahman F, Brates I, Aweeka F, Bosch RJ, Deitchman A, Nixon D, Aberg JA. Evaluating the effect of atorvastatin exposure and vitamin D levels on lipid outcomes in people with HIV-1 with suppressed HIV-1 RNA and LDL cholesterol <130 mg/dL. HIV Med. 2023 Jun;24(6):749-753. doi: 10.1111/hiv.13453. Epub 2022 Dec 22.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20
BG001	Arm B: Placebo / Atorvastatin	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated placebo for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the dose of placebo was doubled at the week 4 visit. At week 20, the placebo was stopped for a 4-week washout period. At week 24, atorvastatin was started at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at week 28. At week 44, atorvastatin was stopped to allow for another 4-week washout period. atorvastatin: Starting at week 24, 10 mg daily for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, 20 mg daily from week 28- week 44.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in log10 IL-6

IL-6 (Interleukin 6) in log10 pg/mL: Difference between [change from week 24 to week 44] and [change from baseline to week 20] (i.e. [week 44 - week 24] - [week 20 - baseline])

The primary analysis was as-treated, limited to participants who had data for baseline, week 20, week 24, and week 44, and remained on study treatment through week 44 (allowing treatment interruption < 4 weeks), and did not use prohibited medications or have virologic failure during the course of the study.

Posted

Median

Inter-Quartile Range

log10 pg/mL

baseline, week 20, week 24, and week 44

ID	Title	Description
OG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20
OG001	Arm B: Placebo / Atorvastatin	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated placebo for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the dose of placebo was doubled at the week 4 visit. At week 20, the placebo was stopped for a 4-week washout period. At week 24, atorvastatin was started at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at week 28. At week 44, atorvastatin was stopped to allow for another 4-week washout period. atorvastatin: Starting at week 24, 10 mg daily for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, 20 mg daily from week 28- week 44.

Units	Counts
Participants	OG00034 OG00136

Title

Denominators

Categories

Title	Measurements
	OG000-0.08(-0.32 to 0.22) OG001-0.08(-0.28 to 0.12)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis is that there is no difference between arm A and arm B in the differences of the changes ([week 44 - week 24] - [week 20 - baseline]) in log10 IL-6	Wilcoxon (Mann-Whitney)	Exact Wilcoxon rank sum test was used	0.94	Two-sided p-values of < 0.05 without adjustments for multiple testing were considered statistically significant.					2-Sided								Superiority or Other (legacy)

Primary

Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in CD4+ T-cell Activation Percent

CD4+ T-cell activation percent (% CD38+/DR+ of CD4+): Difference between [change from week 24 to week 44] and [change from baseline to week 20] (i.e. [week 44 - week 24] - [week 20 - baseline])

Posted

Median

Inter-Quartile Range

percent

baseline, week 20, week 24, and week 44

ID	Title	Description
OG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20
OG001

Primary

Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in log10 D-dimer

D-dimer in log10 ng/mL: Difference between [change from week 24 to week 44] and [change from baseline to week 20] (i.e. [week 44 - week 24] - [week 20 - baseline])

Posted

Median

Inter-Quartile Range

log10 ng/mL

baseline, week 20, week 24, and week 44

ID	Title	Description
OG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20
OG001	Arm B: Placebo / Atorvastatin

Primary

Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in CD8+ T-cell Activation Percent

CD8+ T-cell activation percent (% CD38+/DR+ of CD8+): Difference between [change from week 24 to week 44] and [change from baseline to week 20] (i.e. [week 44 - week 24] - [week 20 - baseline])

Posted

Median

Inter-Quartile Range

percent

baseline, week 20, week 24, and week 44

ID	Title	Description
OG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20
OG001

Secondary

Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in MCP-1 (log10 Transformed)

Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages.

Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

This analysis was as-treated, limited to participants who had data for baseline, week 20, week 24, and week 44, and remained on study treatment through week 44 (allowing treatment interruption < 4 weeks), and did not use prohibited medications or have virologic failure during the course of the study.

Posted

Median

Inter-Quartile Range

log10 pg/ml

baseline, week 20, week 24, and week 44

ID	Title	Description
OG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20

Secondary

Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in IP-10 (log10 Transformed)

IFN-gamma-inducible protein 10 (IP-10 or CXCL10) is a chemokine secreted from cells stimulated with type I and II IFNs and LPS, is also a chemoattractant for activated T cells.

Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

Posted

Median

Inter-Quartile Range

log10 pg/ml

baseline, week 20, week 24, and week 44

ID	Title	Description
OG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20

Secondary

Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in CD40L (log10 Transformed)

Cluster of differentiation 40 (CD40L) is a costimulatory protein found on antigen presenting cells and is required for their activation.

Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

Posted

Median

Inter-Quartile Range

log10 pg/ml

baseline, week 20, week 24, and week 44

ID	Title	Description
OG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20

Secondary

Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in sCD14 (log10 Transformed)

Soluble cluster of differentiation 14 (sCD14) is a human gene. Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

Posted

Median

Inter-Quartile Range

log10 ng/ml

baseline, week 20, week 24, and week 44

ID	Title	Description
OG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20
OG001

Secondary

Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in P-selectin (log10 Transformed)

P-selectin is a protein that in humans encoded by the SELP gene. P-selectin functions as a cell adhesion molecule (CAM) on the surfaces of activated endothelial cells, which line the inner surface of blood vessels, and activated platelets.

Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

Posted

Median

Inter-Quartile Range

log10 ng/ml

baseline, week 20, week 24, and week 44

ID	Title	Description
OG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20

Secondary

Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in sCD163 (log10 Transformed)

CD163 (Cluster of Differentiation 163) is a protein that in humans encoded by the CD163 gene; and sCD163 is soluble CD163.

Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

Posted

Median

Inter-Quartile Range

log10 ng/ml

baseline, week 20, week 24, and week 44

ID	Title	Description
OG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20

Secondary

Number of Participants With Safety Endpoints Before Study Treatment Cross-over (Baseline to Week 24)

Safety endpoints are defined as grade ≥ 2 signs and symptoms, laboratory abnormalities, AST/ALT > 3 X ULN, and adverse events prior to study treatment cross-over (baseline to week 24).

The DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009) was used for grading of AEs.

participants who started study treatment

Posted

Number

participants

week 0 to week 24

ID	Title	Description
OG000	Arm A: Atorvastatin / Placebo	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. atorvastatin: 10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4 - week 20
OG001	Arm B: Placebo / Atorvastatin	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated placebo for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the dose of placebo was doubled at the week 4 visit. At week 20, the placebo was stopped for a 4-week washout period.

Secondary

Number of Participants With Safety Endpoints After Study Treatment Cross-over (Week 24 to Week 48)

Safety endpoints are defined as grade ≥ 2 signs and symptoms, laboratory abnormalities, AST/ALT > 3 X ULN, and adverse events after study treatment cross-over (week 24 to week 48).

The DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009) was used for grading of AEs.

participants who crossed over study treatment at week 24

Posted

Number

participants

week 24 to week 48

ID	Title	Description
OG000	Arm A: Atorvastatin / Placebo	At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period.
OG001	Arm B: Placebo / Atorvastatin	At week 24, atorvastatin was started at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at week 28. At week 44, atorvastatin was stopped to allow for another 4-week washout period. atorvastatin: Starting at week 24, 10 mg daily for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, 20 mg daily from week 28- week 44.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A: Atorvastatin / Placebo Before Cross-over (Week 0 - 24)	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period.	4	46	37	46
EG001	Arm B: Placebo / Atorvastatin Before Cross-over (Week 0 - 24)	At study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated placebo for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the dose of placebo was doubled at the week 4 visit. At week 20, the placebo was stopped for a 4-week washout period.	3	48	44	48
EG002	Arm A: Atorvastatin / Placebo After Cross-over (Week 24 - 48)	At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period.	0	41	30	41
EG003	Arm B: Placebo / Atorvastatin After Cross-over (Week 24 - 48)	At week 24, atorvastatin was started at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at week 28. At week 44, atorvastatin was stopped to allow for another 4-week washout period.	0	43	31	43

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chest discomfort	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected46 at risk EG0010 affected48 at risk EG0020 affected41 at risk EG0030 affected43 at risk
Campylobacter gastroenteritis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected46 at risk EG0010 affected48 at risk EG0020 affected41 at risk EG003
Tooth abscess	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected46 at risk EG0010 affected48 at risk EG0020 affected41 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected46 at risk EG0010 affected48 at risk EG0020 affected41 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected46 at risk EG0011 affected48 at risk EG0020 affected41 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected46 at risk EG0011 affected48 at risk EG0020 affected41 at risk EG003
Depression	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected46 at risk EG0011 affected48 at risk EG0020 affected41 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected46 at risk EG0010 affected48 at risk EG0020 affected41 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected46 at risk EG0015 affected48 at risk EG0023 affected41 at risk EG0030 affected43 at risk
Alanine aminotransferase abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected46 at risk EG0013 affected48 at risk EG0020 affected41 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0004 affected46 at risk EG0013 affected48 at risk EG0023 affected41 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0004 affected46 at risk EG0011 affected48 at risk EG0023 affected41 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0004 affected46 at risk EG0011 affected48 at risk EG0020 affected41 at risk EG003
Blood bicarbonate decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected46 at risk EG0015 affected48 at risk EG0020 affected41 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 18.0	Systematic Assessment	EG00019 affected46 at risk EG00124 affected48 at risk EG0028 affected41 at risk EG003
Blood cholesterol increased	Investigations	MedDRA 18.0	Systematic Assessment	EG00012 affected46 at risk EG00123 affected48 at risk EG00215 affected41 at risk EG003
Blood creatinine increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected46 at risk EG0018 affected48 at risk EG0022 affected41 at risk EG003
Blood glucose decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0004 affected46 at risk EG0015 affected48 at risk EG0023 affected41 at risk EG003
Blood glucose increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0003 affected46 at risk EG0019 affected48 at risk EG0027 affected41 at risk EG003
Blood potassium decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0003 affected46 at risk EG0013 affected48 at risk EG0023 affected41 at risk EG003
Low density lipoprotein increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0007 affected46 at risk EG00118 affected48 at risk EG0028 affected41 at risk EG003
Platelet count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0003 affected46 at risk EG0012 affected48 at risk EG0022 affected41 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected46 at risk EG0012 affected48 at risk EG0021 affected41 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected46 at risk EG0010 affected48 at risk EG0024 affected41 at risk EG003
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected46 at risk EG0012 affected48 at risk EG0020 affected41 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected46 at risk EG0014 affected48 at risk EG0020 affected41 at risk EG003

ID	Term
D011758	Pyrroles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006538	Heptanoic Acids
D005227	Fatty Acids
D008055	Lipids