Leukapheresis Procedures to Obtain Plasma and Lymphocytes for Research Studies on Primary and Chronic HIV-Infected Patients

• ClinicalTrials.gov Identifier: NCT00039689
• Recruitment Status: Recruiting
• First Posted: June 7, 2002
• Last Update Posted: March 27, 2023
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Study Description

Brief Summary:

There is evidence that early and aggressive treatment with antiretroviral drugs can prevent the loss of immune cell function that accompanies HIV infection. This study will use leukapheresis (drawing blood, separating out the white cells and returning the blood to the patient) to obtain blood cells from HIV-infected patients in either the acute or chronic stage of infection who are being treated with early highly active antiretroviral therapy (HAART). Leukapheresis is necessary to obtain enough cells to delineate the response of B cells to CD4+ T cell help, the CD8 factors associated with suppression of viral replication and normalization of immune function, and natural killer function relative to HIV disease.

Study participants will be adult (older than 18 years) HIV primary or acutely affected patients (those with a history of exposure to HIV but not yet showing chronic symptoms of HIV disease) and HIV chronically infected patients (those infected with HIV for longer than 12 months or showing other symptoms of HIV disease) who are not receiving HAART at the beginning of the study. The study seeks to enroll 30 primary and 30 chronic patients. Pregnant women will not be enrolled in the study; women who become pregnant will be dropped from the study.

Leukapheresis will be performed on each patient before HAART therapy begins and then three times a year. Each session will take between 1 and 3 hours.

This longitudinal study will enable researchers to examine the function of certain B cells, natural killer cells, and CD8+ T cells in people who do not have chronic HIV disease and in those who do have the disease and are treated with HAART.

...

Condition or disease
HIV

Detailed Description:

HIV infection is known to cause profound and irreversible dysfunction of both innate and adaptive arms of the immune system. However, there is mounting evidence that early and aggressive treatment with antiretroviral drugs can prevent loss of immune cell function. In an attempt to further delineate the effect of early antiretroviral therapy (ART) on maintenance of immune cell function, we wish to recruit drug-naive HIV-infected patients who are either in early or chronic stage of infection. The study will require that patients undergo leukapheresis or research blood draw once before and several times after enrollment. Leukapheresis will be used in order to obtain sufficient cells to pursue the following objectives: delineating B cell response to CD4+T cell help, delineating the effect of ART on persistent HIV reservoirs in CD4+T cells of infected individuals, and delineating CD8+T cell-mediated suppression of viral replication and normalization of immune function, and characterizing natural killer (NK) function relative to HIV disease. The required number of mononuclear cells needed to perform these experiments can be easily and safely obtained using leukapheresis procedures in the Clinical Center Apheresis Unit. This protocol is specifically designed to conform to the requirements of the Apheresis Unit for donors to have leukapheresis procedures, but the protocol, by itself, is not an independent research study. Alternatively, whole blood draws may be used in cases where patients are unable to undergo leukapheresis. While this approach will limit extensive functional analyses, informative phenotypic and limited functional analyses can nonetheless be performed.

Study Design

• Study Type: Observational
• Estimated Enrollment: 750 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Leukapheresis Procedures to Obtain Plasma and Lymphocytes for Research Studies on Antiretroviral-Naive HIV-Infected Patients
• Actual Study Start Date: July 12, 2002

Groups and Cohorts

Group/Cohort
HIV chronic infection; For example, an individual infected with HIV-1 for an indeterminate amount of time.
HIV early infection; For example, a negative HIV antibody immunoassay within 6 months of a positive HIV antibody assay and confirmatory test (as defined by current CDC criteria).

Outcome Measures

Primary Outcome Measures :

1. To further investigate differences in the immunologic function of various lymphocyte subsets in HIV-infected patients [ Time Frame: Throughout the study ]
   To further investigate differences in the immunologic function of various lymphocyte subsets in HIV-infected patients who are treated early in their infection and during the chronic phase of the infection. Studies will also be done to further delineate the various antigen-specific and innate immune responses including characterization of soluble factors associated with early HIV infection.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Subjects will be recruited from existing cohorts of individuals participating in National Institute of Allergy and Infectious Diseases (NIAID) who meet the Inclusion/Exclusion Criteria. Additional local and regional recruitment may be done using direct mailing to infectious disease physicians, internet ad campaigns, social media outlets, print ads, and from local clinics via the NIAID patient recruitment contract with Matthews Media Group.@@@

Criteria

• INCLUSION CRITERIA:

Adult (18 years old or older) HIV-1-infected patient

Adequate venous access for apheresis or sufficient research blood collection

Positive HIV antibody immunoassay and a positive confirmatory HIV test (as defined by current CDC criteria). Tests may be done in our clinic or by an outside provider. For individuals with suspected early infection; the following additional criteria may be used: HIV RNA levels of >2,000 copies/ml with a negative result from an HIV antibody immunoassay.

Willingness to be able to make follow up visits at least once in the next 4 months and prior to the initiation of antiretroviral therapy.

Blood pressure less than 180/100; pulse rate between 50-100 unless a lower pulse reat is considered normal for the volunteer

Adequate blood counts (hemoglobin greater than or equal to 9.0 g/dL, hematocrit greater than or equal to 28 percent, platelets greaterhan or equal to 50,000).

Willingness to give informed consent including consent for the storage of blood samples and genetic testing.

Antiretroviral naive or no antiretroviral use in the last six months, or previously enrolled 02-I-0202 subjects on whom there are samples stored in the repository. Subjects who become HIV- infected

while taking antiretroviral therapy for pre-exposure prophylaxis (PrEP) will be eligible for enrollment as long as them meet diagnostic criteria for HIV positivity. Subjects who enroll under another LIR apheresis protocol within the past three months and complete

the apheresis prior to starting antiretroviral therapy will also be

eligible for enrollment.

EXCLUSION CRITERIA:

Pregnant and/or breastfeeding women.

Be currently acusing alcohol or other drugs that potentially could interfere with patient compliance or safety.

Have a condition in the opinion of the investigators would make the patient ineligible for the study

Contacts and Locations

Contacts

Contact: Kathleen R Gittens; (301) 435-8003; kathleen.gittens@nih.gov

Contact: Susan Moir, Ph.D.; (301) 402-4559; sm221a@nih.gov

Locations

United States, Maryland

National Institutes of Health Clinical Center; Recruiting

Bethesda, Maryland, United States, 20892

Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY dial 711 ccopr@nih.gov

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Susan Moir, Ph.D.; National Institute of Allergy and Infectious Diseases (NIAID)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

Dubruille J, Meng B, Lerondeau MT. [Fractures to bonded metal ceramics]. Actual Odontostomatol (Paris). 1971 Mar;25(93):59-79. No abstract available. French.

Kanter PM, Schwartz HS. A fluorescence enhancement assay for cellular DNA damage. Mol Pharmacol. 1982 Jul;22(1):145-51.

Holt JH Jr, Barnard AC, Lynn MS. A study of the human heart as a multiple dipole electrical source. II. Diagnosis and quantitation of left ventricular hypertrophy. Circulation. 1969 Nov;40(5):697-710. doi: 10.1161/01.cir.40.5.697. No abstract available.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00039689
• Other Study ID Numbers: 020202; 02-I-0202
• First Posted: June 7, 2002
• Last Update Posted: March 27, 2023
• Last Verified: February 22, 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):

Cellular Immunity; Chronic HIV Infection; Antiretroviral Therapy; Primary HIV Infection; Humoral Immunity; Natural History; HIV Infection; Acute Infection; Treatment Naive