NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

Elite Controller and ART-Treated HIV+ Statin Versus ASA Treatment Intervention Study

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

14-I-0039

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required

Yes

Population Exclusion(s)

Children

Keywords

Treated Progressors;
Immune Activation

Recruitment Keyword(s)

None

Condition(s)

Human Immunodeficiency Virus

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Drug: Aspirin
Drug: Atorvastatin

Supporting Site

National Institute of Allergy and Infectious Diseases

Background:

- The immune system protects the body from infection. But it can also cause harm. For example, the clotting system makes blood clot and protects from bleeding. But blood clots are sometimes harmful. People with human immunodeficiency virus (HIV) infection have increased inflammation and clotting. This may increase their risk for diseases like stroke or heart attack. Researchers want to know how aspirin or HMG-CoA reductase inhibitors (so-called statin medications) affect the immune and clotting systems of people with HIV. Aspirin is a medicine to decrease clotting. Statins are medications given to lower cholesterol and decrease inflammation.

Objectives:

- To see how aspirin or statins change immune and clotting systems in people with HIV.

Eligibility:

- Adults 18 and older with HIV and a low viral load, not on aspirin or a statin medication. They must also have either: (1) never taken anti-HIV medications (ARVs), have a suppressed viral load, have stable CD4 counts, and never had an opportunistic infection; or (2) been taking ARVs for 5 continuous years and have a suppressed viral load for more than 3 years.

Design:

- Participants will be screened with medical history, physical exam, and blood and lab tests.

- Participants will repeat screening tests and have an MRI. An MRI is a way to visualize blood vessels in the neck and head. Participants will lie on a table that slides in and out of a cylinder surrounded by a magnetic field.

- Participants will take either study drug once daily for 9 months.

- Participants will have a blood procedure twice. Blood will be removed through a needle in one arm and circulated through a machine that removes white blood cells. The blood, minus white blood cells, is returned through a needle in the other arm.

- All participants will be observed for 3 months before and after treatment.

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Eligibility

INCLUSION CRITERIA:

EC Arm

1. Age greater than or equal to 18 years.

2. Documented HIV-1 infection confirmed by enzyme-linked immunosorbent assay (ELISA) and Western blot tests (will not be repeated if performed previously at NIH).

3. Categorized as a long term non-progressor EC as defined by viral loads typically less than the LLD of commercially available assays and clinical and laboratory criteria (no OIs, no ART, stable CD4 T cell counts for more than 3 years). Viral load blips are allowed as long as they are less than 500 copies/mL and flanked by viral load measurements less than 100copies/mL. Viral load <100c/mL will be acceptable for eligibility at screening.

4. In women of childbearing potential, with no plans for pregnancy for the next 15 months and willing to use 2 investigator approved highly reliable methods of birth control consistently while on the study or in 3 month follow up.

5. Willingness to have samples stored for future research.

6. Not on a statin or ASA for the past 6 months.

ART <50 Arm

1. Age greater than or equal to 18 years.

2. Documented HIV-1 infection confirmed by enzyme-linked immunosorbent assay (ELISA) and Western blot tests.

3. In women of childbearing potential, with no plans for pregnancy for the next 15 months and willing to use 2 investigator approved highly reliable methods of birth control consistently while on the study or in 3 month follow up.

4. On continuous combination ART >4 years.

5. HIV RNA <50 copies/mL (or less than 40 or less than 48 copies/mL, depending on the lower limit of detection of the assay used; transient periods of low level (<300) detectable virus, blips, acceptable if isolated and followed by viral loads less than the lower limit of detection) >3 years and current HIV-RNA less than the LLD of the commercially available assay used. Subject will be rescreened if HIV is detectable at screening visit.

6. Willingness to have samples stored for future research.

7. Not on a statin or ASA for the past 6 months.

EXCLUSION CRITERIA

1. Diagnosis of cardiovascular disease or hypercholesterolemia (LDL cholesterol 190 mg/dL).

2. Known hypersensitivity or allergy to ATV or ASA, including a history of myositis or rhabdomyolysis with statin or ASA use.

3. Other contraindication for ASA or statin therapy (active liver disease, peptic ulcer disease, etc.).

4. Women who are lactating, pregnant, or actively trying to become pregnant or considering pregnancy over the likely span of the study (including women of childbearing potential who are unwilling to use adequate contraception throughout the study).

5. Any chronic inflammatory condition either requiring anti-inflammatory medication (systemic corticosteroids, daily NSAID use,immunomodulating medications) which may, in the opinion of the investigator, confound the interpretation of soluble inflammatory biomarkers. While on study, short term (less than 5 days) NSAID use will be allowed at the discretion of the investigator.

6. Active drug use or alcohol abuse that, in the opinion of the investigator, may interfere with the ability of the subject to participate in the study or that may unacceptably increase the risk of the study intervention..

7. Safety laboratory cut offs: coagulation (INR >2 upper limit of normal [ULN], PLT<75K), renal function (GFR<60), liver function (ALT or Alkaline phosphatase or direct bilirubin >2x ULN), aldolase <1.5 ULN and anemia (Hg <9 mg/dL).

8. Antiretroviral therapy with tipranivir, or any therapy which combines non-nucleoside reverse transcriptase inhibitors with protease inhibitors.

9. Chronic hepatitis C co-infection. However, if a subject has more than 24 weeks of sustained virologic response (SVR), the subject can be considered for eligibility.

10. If either MR or apheresis is contraindicated, subject may still participate without this procedure. In the case of missed apheresis, a 30 mL research blood draw will be substituted (see Appendices B and C).

- If statin initiation is indicated per current guidelines, subject will be counseled to consult with their PMD. If the subject then chooses to take part in the study, we will provide their PMD with all pertinent lab results during the course of the study, if requested.

Co-enrollment Guidelines: Co-enrollment in other trials will be restricted, other than enrollment on observational studies. Study staff should be notified of co-enrollment as it may require the approval of the Investigator.


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Citations:

Deeks SG, Phillips AN. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ. 2009 Jan 26;338:a3172. doi: 10.1136/bmj.a3172.

Krishnan S, Wilson EM, Sheikh V, Rupert A, Mendoza D, Yang J, Lempicki R, Migueles SA, Sereti I. Evidence for innate immune system activation in HIV type 1-infected elite controllers. J Infect Dis. 2014 Mar;209(6):931-9. doi: 10.1093/infdis/jit581. Epub 2013 Nov 1.

Funderburg NT, Mayne E, Sieg SF, Asaad R, Jiang W, Kalinowska M, Luciano AA, Stevens W, Rodriguez B, Brenchley JM, Douek DC, Lederman MM. Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation. Blood. 2010 Jan 14;115(2):161-7. doi: 10.1182/blood-2009-03-210179. Epub 2009 Oct 14.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Irini Sereti, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
NIHBC 10 - CLINICAL CENTER BG RM 11B17
10 CENTER DR
BETHESDA MD 20892
(301) 496-5533
isereti@niaid.nih.gov

Irini Sereti, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
NIHBC 10 - CLINICAL CENTER BG RM 11B17
10 CENTER DR
BETHESDA MD 20892
(301) 496-5533
isereti@niaid.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT02081638

--Back to Top--

NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

Elite Controller and ART-Treated HIV+ Statin Versus ASA Treatment Intervention Study

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

14-I-0039

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required

Yes

Population Exclusion(s)

Children

Keywords

Treated Progressors;
Immune Activation

Recruitment Keyword(s)

None

Condition(s)

Human Immunodeficiency Virus

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Drug: Aspirin
Drug: Atorvastatin

Supporting Site

National Institute of Allergy and Infectious Diseases

Background:

- The immune system protects the body from infection. But it can also cause harm. For example, the clotting system makes blood clot and protects from bleeding. But blood clots are sometimes harmful. People with human immunodeficiency virus (HIV) infection have increased inflammation and clotting. This may increase their risk for diseases like stroke or heart attack. Researchers want to know how aspirin or HMG-CoA reductase inhibitors (so-called statin medications) affect the immune and clotting systems of people with HIV. Aspirin is a medicine to decrease clotting. Statins are medications given to lower cholesterol and decrease inflammation.

Objectives:

- To see how aspirin or statins change immune and clotting systems in people with HIV.

Eligibility:

- Adults 18 and older with HIV and a low viral load, not on aspirin or a statin medication. They must also have either: (1) never taken anti-HIV medications (ARVs), have a suppressed viral load, have stable CD4 counts, and never had an opportunistic infection; or (2) been taking ARVs for 5 continuous years and have a suppressed viral load for more than 3 years.

Design:

- Participants will be screened with medical history, physical exam, and blood and lab tests.

- Participants will repeat screening tests and have an MRI. An MRI is a way to visualize blood vessels in the neck and head. Participants will lie on a table that slides in and out of a cylinder surrounded by a magnetic field.

- Participants will take either study drug once daily for 9 months.

- Participants will have a blood procedure twice. Blood will be removed through a needle in one arm and circulated through a machine that removes white blood cells. The blood, minus white blood cells, is returned through a needle in the other arm.

- All participants will be observed for 3 months before and after treatment.

--Back to Top--

Eligibility

INCLUSION CRITERIA:

EC Arm

1. Age greater than or equal to 18 years.

2. Documented HIV-1 infection confirmed by enzyme-linked immunosorbent assay (ELISA) and Western blot tests (will not be repeated if performed previously at NIH).

3. Categorized as a long term non-progressor EC as defined by viral loads typically less than the LLD of commercially available assays and clinical and laboratory criteria (no OIs, no ART, stable CD4 T cell counts for more than 3 years). Viral load blips are allowed as long as they are less than 500 copies/mL and flanked by viral load measurements less than 100copies/mL. Viral load <100c/mL will be acceptable for eligibility at screening.

4. In women of childbearing potential, with no plans for pregnancy for the next 15 months and willing to use 2 investigator approved highly reliable methods of birth control consistently while on the study or in 3 month follow up.

5. Willingness to have samples stored for future research.

6. Not on a statin or ASA for the past 6 months.

ART <50 Arm

1. Age greater than or equal to 18 years.

2. Documented HIV-1 infection confirmed by enzyme-linked immunosorbent assay (ELISA) and Western blot tests.

3. In women of childbearing potential, with no plans for pregnancy for the next 15 months and willing to use 2 investigator approved highly reliable methods of birth control consistently while on the study or in 3 month follow up.

4. On continuous combination ART >4 years.

5. HIV RNA <50 copies/mL (or less than 40 or less than 48 copies/mL, depending on the lower limit of detection of the assay used; transient periods of low level (<300) detectable virus, blips, acceptable if isolated and followed by viral loads less than the lower limit of detection) >3 years and current HIV-RNA less than the LLD of the commercially available assay used. Subject will be rescreened if HIV is detectable at screening visit.

6. Willingness to have samples stored for future research.

7. Not on a statin or ASA for the past 6 months.

EXCLUSION CRITERIA

1. Diagnosis of cardiovascular disease or hypercholesterolemia (LDL cholesterol 190 mg/dL).

2. Known hypersensitivity or allergy to ATV or ASA, including a history of myositis or rhabdomyolysis with statin or ASA use.

3. Other contraindication for ASA or statin therapy (active liver disease, peptic ulcer disease, etc.).

4. Women who are lactating, pregnant, or actively trying to become pregnant or considering pregnancy over the likely span of the study (including women of childbearing potential who are unwilling to use adequate contraception throughout the study).

5. Any chronic inflammatory condition either requiring anti-inflammatory medication (systemic corticosteroids, daily NSAID use,immunomodulating medications) which may, in the opinion of the investigator, confound the interpretation of soluble inflammatory biomarkers. While on study, short term (less than 5 days) NSAID use will be allowed at the discretion of the investigator.

6. Active drug use or alcohol abuse that, in the opinion of the investigator, may interfere with the ability of the subject to participate in the study or that may unacceptably increase the risk of the study intervention..

7. Safety laboratory cut offs: coagulation (INR >2 upper limit of normal [ULN], PLT<75K), renal function (GFR<60), liver function (ALT or Alkaline phosphatase or direct bilirubin >2x ULN), aldolase <1.5 ULN and anemia (Hg <9 mg/dL).

8. Antiretroviral therapy with tipranivir, or any therapy which combines non-nucleoside reverse transcriptase inhibitors with protease inhibitors.

9. Chronic hepatitis C co-infection. However, if a subject has more than 24 weeks of sustained virologic response (SVR), the subject can be considered for eligibility.

10. If either MR or apheresis is contraindicated, subject may still participate without this procedure. In the case of missed apheresis, a 30 mL research blood draw will be substituted (see Appendices B and C).

- If statin initiation is indicated per current guidelines, subject will be counseled to consult with their PMD. If the subject then chooses to take part in the study, we will provide their PMD with all pertinent lab results during the course of the study, if requested.

Co-enrollment Guidelines: Co-enrollment in other trials will be restricted, other than enrollment on observational studies. Study staff should be notified of co-enrollment as it may require the approval of the Investigator.


--Back to Top--

Citations:

Deeks SG, Phillips AN. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ. 2009 Jan 26;338:a3172. doi: 10.1136/bmj.a3172.

Krishnan S, Wilson EM, Sheikh V, Rupert A, Mendoza D, Yang J, Lempicki R, Migueles SA, Sereti I. Evidence for innate immune system activation in HIV type 1-infected elite controllers. J Infect Dis. 2014 Mar;209(6):931-9. doi: 10.1093/infdis/jit581. Epub 2013 Nov 1.

Funderburg NT, Mayne E, Sieg SF, Asaad R, Jiang W, Kalinowska M, Luciano AA, Stevens W, Rodriguez B, Brenchley JM, Douek DC, Lederman MM. Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation. Blood. 2010 Jan 14;115(2):161-7. doi: 10.1182/blood-2009-03-210179. Epub 2009 Oct 14.

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Irini Sereti, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
NIHBC 10 - CLINICAL CENTER BG RM 11B17
10 CENTER DR
BETHESDA MD 20892
(301) 496-5533
isereti@niaid.nih.gov

Irini Sereti, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
NIHBC 10 - CLINICAL CENTER BG RM 11B17
10 CENTER DR
BETHESDA MD 20892
(301) 496-5533
isereti@niaid.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT02081638

--Back to Top--