Treatment De-Intensification and Residual HIV-1 in Youth - Full Text View

Sponsor:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators:	National Institute on Drug Abuse (NIDA) National Institute of Mental Health (NIMH)
Information provided by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00867854

Purpose

This laboratory-based sub-study of ATN 061 and ATN 071 will examine the effect of early treatment followed by treatment de-intensification to atazanavir/ritonavir (ATV/r) monotherapy on steady-state frequencies of replication-competent CD4+ T cell Human Immunodeficiency Virus (HIV)-1 reservoirs or cell-associated infectivity (CAI) and persistent low-level viremia (LLV), and their contribution to successful long-term control of HIV-1 replication among HIV-1 infected adolescents and young adults.

Condition	Intervention
HIV-1 HIV Infections	Other: Blood draw

Study Type:	Observational
Study Design:	Case Control, Prospective
Official Title:	Treatment De-Intensification and Residual HIV-1 in Adolescents and Young Adults: A Sub-Study of ATN 061 and ATN 071.

Resource links provided by NLM:

MedlinePlus related topics: AIDS

U.S. FDA Resources

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:

Steady-state frequencies of replication-competent CD4+ T cell HIV-1 reservoirs in participants starting HAART before DHHS guidelines (CD4+ T cell levels < 350 cells/mm3) vs. those initiating HAART by current DHHS guidelines. [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]
Quantitative changes in LLV between 6.5 and 50 copies/ml in participants starting early therapy & de-intensifying to ATV/r monotherapy vs. those initiating HAART at CD4+ T cell levels < 350 cells/mm3 & maintaining standard HAART. [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]
Quantitative changes in viral diversity during HAART in participants initiating early therapy & de-intensifying to ATV/r monotherapy vs those initiating HAART at CD4+ T cell levels < 350 cells/mm3 & maintaining standard HAART. [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]
Effect of viral diversity in replication-competent CD4+ T cell reservoirs & low viremia variants before de-intensification on successful control of HIV-1 replication during ATV/r maintenance in participants starting HAART before DHHS guidelines. [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To examine the contribution of LLV genotypes, through analysis of the Gag/protease and RT, among subjects who developed rebound viremia above 50 copies/ml during treatment de-intensification to ATV/r. [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]

Biospecimen Retention: Samples With DNA

Biospecimen Description:

Whole blood

Estimated Enrollment:	50
Study Start Date:	February 2009
Estimated Study Completion Date:	May 2011
Estimated Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Experimental 25 evaluable subjects from the experimental arm of ATN 061 who undergo de-intensification to boosted atazanavir (ATV) with VL suppression of < 100 copies/ml and CD4+ T cells > 350 cells/mm3 at week 48 and maintain VL suppression to < 400 copies/ml with stable CD4+ T cell counts after week 48.	Other: Blood draw This sub-study does not involve additional treatment of any ATN 061 or ATN 071 study subjects. The only intervention involved is the requirement for whole blood collection (40 ml and 60 ml) to be drawn at the same time as four ATN 061 study visits (36, 48, 56, and 80 weeks) for subjects co-enrolled into ATN 061. When these time points coincide with ATN 061 Central Laboratory samples, the 60 ml blood sample will not be collected. For subjects co-enrolled into ATN 071, there are also two samples of whole blood collection (40 ml and 60 ml) required to be drawn at four time points but at weeks 36, 48, 56, and 80 after the initiation of HAART.
Control 25 evaluable subjects from ATN 071 will also be enrolled. These subjects will have initiated HAART according to current DHHS guidelines (CD4+ T cells < 350 cells/mm3), had viral load suppression to < 100 copies/ml at 24 through 48 weeks on HAART and maintained suppression to < 400 copies/ml through week 80.	Other: Blood draw This sub-study does not involve additional treatment of any ATN 061 or ATN 071 study subjects. The only intervention involved is the requirement for whole blood collection (40 ml and 60 ml) to be drawn at the same time as four ATN 061 study visits (36, 48, 56, and 80 weeks) for subjects co-enrolled into ATN 061. When these time points coincide with ATN 061 Central Laboratory samples, the 60 ml blood sample will not be collected. For subjects co-enrolled into ATN 071, there are also two samples of whole blood collection (40 ml and 60 ml) required to be drawn at four time points but at weeks 36, 48, 56, and 80 after the initiation of HAART.

Groups/Cohorts

Assigned Interventions

Experimental

25 evaluable subjects from the experimental arm of ATN 061 who undergo de-intensification to boosted atazanavir (ATV) with VL suppression of < 100 copies/ml and CD4+ T cells > 350 cells/mm3 at week 48 and maintain VL suppression to < 400 copies/ml with stable CD4+ T cell counts after week 48.

Other: Blood draw

This sub-study does not involve additional treatment of any ATN 061 or ATN 071 study subjects. The only intervention involved is the requirement for whole blood collection (40 ml and 60 ml) to be drawn at the same time as four ATN 061 study visits (36, 48, 56, and 80 weeks) for subjects co-enrolled into ATN 061. When these time points coincide with ATN 061 Central Laboratory samples, the 60 ml blood sample will not be collected. For subjects co-enrolled into ATN 071, there are also two samples of whole blood collection (40 ml and 60 ml) required to be drawn at four time points but at weeks 36, 48, 56, and 80 after the initiation of HAART.

Control

25 evaluable subjects from ATN 071 will also be enrolled. These subjects will have initiated HAART according to current DHHS guidelines (CD4+ T cells < 350 cells/mm3), had viral load suppression to < 100 copies/ml at 24 through 48 weeks on HAART and maintained suppression to < 400 copies/ml through week 80.

Other: Blood draw

This sub-study does not involve additional treatment of any ATN 061 or ATN 071 study subjects. The only intervention involved is the requirement for whole blood collection (40 ml and 60 ml) to be drawn at the same time as four ATN 061 study visits (36, 48, 56, and 80 weeks) for subjects co-enrolled into ATN 061. When these time points coincide with ATN 061 Central Laboratory samples, the 60 ml blood sample will not be collected. For subjects co-enrolled into ATN 071, there are also two samples of whole blood collection (40 ml and 60 ml) required to be drawn at four time points but at weeks 36, 48, 56, and 80 after the initiation of HAART.

Eligibility

Ages Eligible for Study:	18 Years to 24 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Twenty-five subjects enrolled in Arm A of ATN 061 who started highly-active antiretroviral therapy (HAART) at CD4+ T cells > 350 cells/cubic millimeter (mm3) and are undergoing treatment de-intensification at week 48 of HAART.

Twenty-five "control" subjects initiating HAART based on current Department of Health and Human Services (DHHS) guidelines at CD4+ T cell levels < 350 cells/mm3 and maintained on standard HAART.

Criteria

081 participants must first be enrolled in either ATN 061 or ATN 071 and meet the eligibility criteria of those protocols in addition to those below.

Inclusion Criteria:

061 Participants

Currently on treatment with an ATV/r-based HAART regimen (ATV/r, FTC, TDF is the preferred regimen);
HIV-1 viral load < 100 copies at week 24;
CD4+ T cell count > 350 cells/mm3 at week 24; and
Able to provide informed consent for the sub-study and adhere to the protocol.

071 Participants
Initiated HAART according to current DHHS guidelines (CD4+ T cells < 350 cells/ mm3);
Currently on treatment with a PI-containing HAART regimen; subjects taking a protease inhibitor OTHER than ATV/r must receive approval by the team via the ATN QNS;
Plasma HIV-1 viral load < 100 copies at week 24 on HAART; measurement to be collected from clinical care results contained in the medical record at the clinical site within +/- 30 days of week 24 on therapy;
CD4+ T cell count > 350 cells/mm3 at week 24 on HAART; measurement to be collected from clinical care results contained in the medical record at the clinical site within +/- 30 days of week 24 on therapy; and
Able to provide informed consent for the sub-study and adhere to the protocol.

General Exclusion Criteria:

Currently enrolled in the Standard Care Arm of ATN 061;
Pregnancy or breast feeding;
Severe (Grade ≥ 3) anemia or other conditions that would not allow adequate blood volume to be drawn;
Active treatment for systemic infections;
Treatment with immune modulators, including immunosuppressive or immune modulating therapy (IL-2, intravenous gammaglobulin, and therapeutic or other experimental vaccines including HIV-1 vaccine given for primary prevention at any time (short courses (<14 days) of prednisone for reactive airway disease (RAD) are permitted);
Active hepatitis B infection as defined by Hepatitis B antigen (Ag) positive;
Disallowed Medications (see Section 5.3.2);
Active drug or alcohol use or dependence that, in the opinion of the site personnel, would interfere with adherence to the study; or
History of chronic renal insufficiency or Grade 3 or greater serum creatinine.

061-Specific Exclusion Criteria
History of an Acquired Immunodeficiency Syndrome (AIDS)-defining illness;
Meets any ATN 061 exclusion criteria for de-intensification; or
Meets any ATN 061 premature study discontinuation criteria.

071-Specific Exclusion Criteria: None

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00867854

Contacts

Contact: Julie Davidson, MSN

301-610-5521

juliedavidson@westat.com

Locations

United States, California
Children's Hospital of Los Angeles	Recruiting
Los Angeles, California, United States, 90027
Contact: Cathy Salata, RN 323-669-2390 csalata@chla.usc.edu
Contact: Diane Tucker , RN, MSN 323-660-2450 ext 3914 dtucker@chla.usc.edu
Principal Investigator: Marvin Belzer, MD
University of California at San Francisco	Not yet recruiting
San Francisco, California, United States, 94118
Contact: J.B. Molaghan, NP 415-514-2434 molaghanj@peds.ucsf.edu
Principal Investigator: Barbara Moscicki, MD
United States, District of Columbia
Children's National Medical Center	Not yet recruiting
Washington, District of Columbia, United States, 20010
Contact: Connie Trexler, RN 202-884-3714
Principal Investigator: Lawrence D'Angelo, MD, MPH
United States, Florida
Children's Diagnostic and Teatment Center	Recruiting
Fort Lauderdale, Florida, United States, 33316
Contact: Esmine Leonard, RN, BSN 954-728-1080 eleonard@nbhd.org
Contact: Amy Inman, BS 954-728-1050 ainman@nbhd.org
Principal Investigator: Ana Puga, MD
University of Miami School of Medicine	Recruiting
Miami, Florida, United States, 33101
Contact: Donna Maturo 305-243-3442 dmaturo@med.miami.edu
Principal Investigator: Lawrence Friedman, MD
University of South Florida College of Medicine	Recruiting
Tampa, Florida, United States, 33606
Contact: Silvia Callejas, BSN 813-259-8800 scalleja@hsc.usf.edu
Contact: Priscilla Julian, RN 813-259-8613 pjulian@hsc.usf.edu
Principal Investigator: Patricia Emmanuel, MD
United States, Illinois
Children's Memorial Hospital	Recruiting
Chicago, Illinois, United States, 60614
Contact: Robert Garafalo, MD 773-388-8661 rgarofalo@childrensmemorial.org
Principal Investigator: Robert Garofalo, MD
John Stroger Jr. Hospital of Cook County	Recruiting
Chicago, Illinois, United States, 60612
Contact: Kelly Bojan 312-572-4571 kbojan@sbcglobal.net
Principal Investigator: Jaime Martinez, MD
United States, Louisiana
Tulane Medical Center	Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Leslie Kozina, CCRC 504-988-5348 lkozina@tulane.edu
Principal Investigator: Sue Ellen Abdalian, MD
United States, Maryland
University of Maryland	Recruiting
Baltimore, Maryland, United States, 21201
Contact: Leonel Flores, MD 410-706-3230 jlflores@peds.umaryland.edu
Principal Investigator: Ligia Peralta, MD
United States, New York
Montefiore Medical Center	Recruiting
Bronx, New York, United States, 10467
Contact: Elizabeth Enriquez-Bruce, MD 718-882-0023 enriquezb@adolescentaids.org
Principal Investigator: Donna Futterman, MD
Mount Sinai Medical Center	Recruiting
New York, New York, United States, 10128
Contact: Mary Geiger, RN 212-423-2867 mary.geiger@msssm.edu
Principal Investigator: Linda Levin Carmine, MD
United States, Pennsylvania
Children's Hospital of Philadelphia	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Mary Tanney, RN, MSN 215-590-4954 tanney@email.chop.edu
Principal Investigator: Steven Douglas, MD
United States, Tennessee
St. Jude Children's Research Hospital	Recruiting
Memphis, Tennessee, United States, 38105
Contact: Mary Dillard, BSN 901-495-4083 mary.dillard@stjude.org
Principal Investigator: Pat Flynn, MD
Puerto Rico
University of Puerto Rico	Recruiting
San Juan, Puerto Rico, 00927
Contact: Anne Fuentes Gomez 787-759-9595 atfuentes@rcm.upr.edu
Principal Investigator: Irma Febo, MD

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

Investigators

Study Chair:

Deborah Persaud, M.D.

Adolescent Trials Network

More Information

Additional Information:

ATN website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Adolescent Trials Network ( James Korelitz, PhD )
Study ID Numbers:	ATN 081
Study First Received:	March 22, 2009
Last Updated:	January 13, 2010
ClinicalTrials.gov Identifier:	NCT00867854 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

de-intensification
HAART
monotherapy
persistent low-level viremia (LLV)
treatment experienced

Additional relevant MeSH terms:

Virus Diseases
Sexually Transmitted Diseases, Viral
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Infection
Retroviridae Infections
Immunologic Deficiency Syndromes

ClinicalTrials.gov processed this record on February 08, 2010