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Protocol Details

Effect of Interferon Alpha 2b Intensification on HIV-1 Residual Viremia in Individuals Suppressed on Antiretroviral Therapy

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

11-I-0057

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18
Max Age: 65

Referral Letter Required

No

Population Exclusion(s)

Children

Keywords

HIV;
Peg-Inferon

Recruitment Keyword(s)

HIV

Condition(s)

HIV

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Drug: Pegylated Interferon Alpha 2b (PEGINTRON)

Supporting Site

National Institute of Allergy and Infectious Diseases

Background:

- Antiretroviral therapy (ART) has been able to improve the lifespan of individuals infected with human immunodeficiency virus type 1 (HIV-1), but ART requires continuous treatment that has substantial consequences on quality of life. ART suppresses HIV-1 virus levels below the limits of detection in current tests, but does not completely eradicate the virus from the blood. Recent research is attempting to determine whether this persistent infection stems from a low-level infection where new cells are continually infected with HIV, or from cells that live for a long time after infection. ART is very active against the virus in new cells, but has no effect on long-lived cells that are already infected with HIV-1 at the start of ART. As a result, new strategies may be necessary to reduce or eradicate these 'reservoir' cells.

- Interferon is a natural substance made by the body to combat virus infections, but can also be made as an injectable drug known as PEGINTRON. PEGINTRON injections have been approved to treat hepatitis C infection, including in patients with HIV infection. Earlier studies of HIV-infected individuals who were not on any ART showed that interferon reduced the level of HIV in the blood. Researchers are interested in determining whether PEGINTRON therapy will also reduce the residual low levels of HIV in patients who are already taking ART.

Objectives:

- To evaluate the effectiveness of PEGINTRON injections on HIV levels in participants currently undergoing antiretroviral therapy.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with HIV, are currently undergoing antiretroviral therapy, and have maintained HIV virus blood counts that are not detectable by current commercial tests for at least 12 months before the start of the study.

Design:

- This study will involve separate screening and treatment processes.

- Participants will be screened with a physical examination and medical history, including blood and urine samples. The screening analysis to determine study eligibility will take several weeks. Participants will have apheresis to provide sufficient numbers of blood cells for evaluation by the study researchers.

- Eligible participants will begin a 4-week course of PEGINTRON injections using the standard dose of PEGINTRON that is approved for treatment of chronic hepatitis C. Participants will have weekly injections and have frequent blood tests to measure HIV virus levels.

- Participants who experience problems in maintaining safe numbers of white blood cells during the study may receive injections of filgrastim to increase their white blood cell count.

- After the 4 weeks of treatment, participants will return for additional blood tests on study days 28, 35, 42, 49, 56, and 84, and Weeks 16, 24, 36, and 48 (i.e., through the end of 1 year after the start of the study).

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Eligibility

INCLUSION CRITERIA:

To be eligible for study participation, a volunteer must satisfy all of the following inclusion criteria:

1. Age greater than or equal to 18 years.

2. Documentation of HIV-1 infection by any licensed ELISA test and confirmed by a Western Blot.

3. Receiving a DHHS-approved ARV regimen.

4. Level of cell-associated HIV RNA greater than or equal to 5 copies/million peripheral blood mononuclear cells (PBMC) done at screening visit 1.

5. HIV-1 RNA levels less than detectable by current commercial means (e.g., Roche Amplicor, b-DNA test) for a minimum of 12 months prior to screening at all time points, and with at least 2 measurements in this 12 month window.

6. CD4 greater than or equal to 300 cells/mm(3) at pre-entry visit within 14 days prior to enrollment.

7. Ability to sign informed consent and willingness to comply with the study requirements and clinic policies.

8. No evidence of viral hepatitis co-infection as assessed by Hepatitis C antibody, HCV RNA, and hepatitis B surface antigen; determinations at pre-entry visit within 28 days prior to enrollment.

9. No history of or evidence of autoimmune hepatitis or other autoimmune disorders at screening, or Antinuclear antibody (ANA > 3 times upper limit of normal.

10. Laboratory values at pre-entry visit within 14 days prior to enrollment:

-Alkaline phosphatase <2.0 times upper limit of normal

-Alanine transaminase (ALT) <2.0 times upper limit of normal

-Total bilirubin < 2.5 mg/dL (< 40 mg/dL if on Atazanavir)

-Creatinine clearance greater than or equal to 60 mL/min as estimated by the Cockcroft-Gault equation

-Neutrophil count greater than or equal 1500 cells/mm(3)

-Platelets greater than or equal to 150,000/ mm(3)

-Hemoglobin greater than or equal to 12.0 mg/dL for men and >11.0 g/dL for women

-Fasting glucose < 126 mg/dL

11. No history or evidence of significant clinical depression at screening that in the opinion of the investigator would affect the ability of the patient to participate in the study, or which would constitute a threat for his/her health in case of relapse upon INF treatment. The Beck Depression Inventory score must be less than or equal to 13 at pre-entry visit.

12. No history of INF/PEG-INF therapy.

13. If capable of pregnancy: use of effective contraception during study: effective contraception methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or use of hormonal contraception with an anti-HIV regimen that will not alter metabolism of hormonal contraception.

14. Participants must have primary medical care outside this protocol: participants will have to provide Primary Care Doctor s contact information.

EXCLUSION CRITERIA:

A volunteer will be ineligible to participate in this study if any of the following criteria are met:

1. History of neoplastic disease requiring cytotoxic therapy including hydroxyurea.

2. Use of long-term systemic corticosteroids, immunosuppressive agents, or cytotoxic agents within 60 days prior to enrollment.

3. Any vaccination within 30 days prior to enrollment. Individuals interested in participating who require vaccination will delay screening until 30 day period is completed.

4. Concurrent therapy with investigational cytokines including IL-2 or IL-12 during the course of the study. Prior administration of cytokines is not an exclusion criterion; at least 4 months from most recent cycle of IL-2 or IL-12 is required.

5. Any febrile illness (>38 degrees C) in the 3 weeks prior to enrollment or any acute therapy for a serious infection completed within 30 days prior to enrollment.

6. Current pregnancy or lactation, history of pregnancy in the last 4 months.

7. Preexisting autoimmune disorders including inflammatory bowel diseases, psoriasis, idiopathic thrombocytopenic purpura, lupus erythematous, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, and optic neuritis.

8. History of severe retinopathy or evidence of severe retinopathy judged by pre-entry ophthalmologic examination.

9. Known allergy/sensitivity to study drug or its formulation.

10. History of seizure disorders or current anticonvulsant use.

11. Any history of medical conditions associated with chronic liver disease (genetic hemochromatosis, alcoholic liver disease, toxin exposures, and autoimmune hepatitis) or documented cirrhosis due to any cause.

12. History of pulmonary disease associated with functional limitation.

13. Documented history of thyroid disease.

14. Active drug or alcohol use or dependence, which in the opinion of the investigator, would interfere with complying with the study requirements.

15. Known hypersensitivity to Escherichia coli-derived products such as filgrastim.

16. Any systemic illness that will make it unlikely that the subject will be able to return for the required study visits.

17. History of, or any condition that in the opinion of the investigator would interfere with the conduct of the study, or it would not be in the best interest of the subject to enroll in this study.


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Citations:

Palmer S, Maldarelli F, Wiegand A, Bernstein B, Hanna GJ, Brun SC, Kempf DJ, Mellors JW, Coffin JM, King MS. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3879-84. doi: 10.1073/pnas.0800050105. Epub 2008 Mar 10.

Maldarelli F, Palmer S, King MS, Wiegand A, Polis MA, Mican J, Kovacs JA, Davey RT, Rock-Kress D, Dewar R, Liu S, Metcalf JA, Rehm C, Brun SC, Hanna GJ, Kempf DJ, Coffin JM, Mellors JW. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 2007 Apr;3(4):e46.

Dinoso JB, Kim SY, Wiegand AM, Palmer SE, Gange SJ, Cranmer L, O'Shea A, Callender M, Spivak A, Brennan T, Kearney MF, Proschan MA, Mican JM, Rehm CA, Coffin JM, Mellors JW, Siliciano RF, Maldarelli F. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9403-8. doi: 10.1073/pnas.0903107106. Epub 2009 May 22.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Frank Maldarelli, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
NIHBC 10 - CLINICAL CENTER BG RM 2B38
10 CENTER DR
BETHESDA MD 20892
(301) 846-5611
fmalli@mail.nih.gov

Jessica M. Earhart
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 2B38A-2
10 Center Drive
Bethesda, Maryland 20892
(240) 858-7504
jessica.earhart@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:

NCT01295515

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