Clinical trial NCT00867854: Treatment De-Intensification and Residual HIV-1 in Youth
Official title: Treatment De-Intensification and Residual HIV-1 in Adolescents and Young Adults: A Sub-Study of ATN 061 and ATN 071.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV-1
HIV Infections
Keywords: de-intensification
HAART
monotherapy
persistent low-level viremia (LLV)
treatment experienced
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: National Institute of Mental Health (NIMH)
First posted: 2009-03-24
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 24
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: 80 weeks
measure: 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.
timeFrame: 80 weeks
measure: 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.
timeFrame: 80 weeks
measure: 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.
timeFrame: 80 weeks
Secondary outcomes:
measure: 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.
timeFrame: 80 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Howard University - IMPAACT Site
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Children's Diagnostic and Teatment Center
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Tampa
country: United States
facility: University of South Florida College of Medicine
state: Florida
city: Chicago
country: United States
facility: John Stroger Jr. Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University - IMPAACT Site
state: Maryland
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
Study officials:
affiliation: Adolescent Trials Network
name: Deborah Persaud, M.D.
role: STUDY_CHAIR
References: