HIV Resistance and Treatment Strategies

NCT00581802 | Completed

• 2 other identifiers: 1R43AI062473-01CURE
• Study Type: observational
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this observational study is to characterize which immune system cells hide the latent reservoir of HIV by counting the number of latent HIV in different subsets of CD4 cells. Observations will also be made on other possible mechanisms of HIV persistence by looking at cellular factors such as APOBEC3 and drug transporters. The purpose of this study is to develop new strategies to reduce and possibly eliminate the latent reservoir in HIV infected adults.

Conditions

HIV Infections

Keywords

CD4-Positive T-Lymphocytes; Treatment Naive; Latent HIV Infections

Outcome Measures

Primary Outcomes (1)

• Establishment of a longitudinal, observational cohort of chemotherapeutically suppressed HIV participants to study cellular and virologic characteristics that enable HIV latency

  At the end of the study

Secondary Outcomes (7)

• Characterization of memory CD4 cell subsets isolated from chemotherapeutically suppressed participants

  At the end of the study

• Quantification of the amount of latent HIV in each memory cell type in chemotherapeutically suppressed participants

  At the end of the study

• Evidence of HIV evolution

  At the end of the study

• Characterization of certain proteins in memory CD4-cell subsets in chemotherapeutically suppressed participants

  At the end of the study

• Determination of the association of protein regulation with cellular toxicity and the latent HIV reservoir in chemotherapeutically suppressed participants

  At the end of the study

Study Arms (5)

1

Intensively studied participants initiating potentially suppressive drug therapy. Group 1 participants may undergo optional leukapheresis. Group 1 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 1 participants will default to either Group 3 or Group 4.

2

Intensively studied, well-suppressed participants on HAART. Participants in Group 2 may undergo optional leukapheresis. Group 2 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 2 participants will default to either Group 3 or Group 4.

3

Nonintensively studied participants initiating potentially suppressive drug therapy

4

Nonintensively studied well-suppressed participants on HAART

5

Intensively studied participants who are currently participating in the Merck Expanded Access Program and receiving raltegravir. Participants in Group 5 may undergo optional leukapheresis. Group 5 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 5 participants will default to either Group 3 or Group 4.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the Comprehensive Care Clinic, a clinic that provides care exclusively to HIV patients from middle Tennessee and surrounding states. Participants are screened and identified with the inclusion and exclusion criteria from the computerized medical records system. If the medical charts are tagged, the study nurse will speak to the selected participant at the participant's following appointment.

You may qualify if:

• HIV infected
• Antiretroviral therapy (ART) naive OR a history of treatment with highly active antiretroviral therapy (HAART), a currently detectable viral load greater than 500 copies/ml, about to begin second or later potentially suppressive antiretroviral regimen, and must meet the following two requirements:
• Viral load less than 50 copies/ml on the immediately prior regimen with less than 50 copies/ml measured on at least two visits during prior ART
• Viral load greater than 500 copies/ml on two consecutive visits and a history of failure during prior lamivudine- or emtricitabine-containing ART

You may not qualify if:

• History of treatment with any two of the following: darunavir, tipranavir, or enfuvirtide
• Self-reported or clinician-reported nonadherence to earlier ART
• Current substance abuse that, in the opinion of the investigator, will increase the risk of nonadherence
• Weight less than 110 lbs
• Blood transfusion within the 6 months prior to study entry
• Platelets less than 50 cells/mm3
• International normalized ratio (INR) greater than 2.0 if participants are on warfarin
• Heart disease with recent angina or myocardial infarction (MI) within 1 year prior to study entry
• Hematocrit 28% or less OR hemoglobin 8.0 g/dl or less
• Prior ART that included only one or two drugs
• Pregnancy
• HIV infected
• Currently on HAART with an undetectable viral load of less than 50 copies/ml for 12 months prior to study entry (at least two measures). If the participant is on the second or later regimen of HAART, the previous regimen must have contained lamivudine or emtricitabine.
• Viral load "blip" greater than 2,000 copies/ml during current suppressive regimen
• Consistent low level viral load (between 50 and 2,000 copies/ml) during current regimen

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Vanderbilt University School of Medicine: collaborator

Study Sites (1)

Comprehensive Care Clinic/Center for AIDS Research

Nashville, Tennessee, 37203, United States

Location

Related Publications (4)

• Noe A, Plum J, Verhofstede C. The latent HIV-1 reservoir in patients undergoing HAART: an archive of pre-HAART drug resistance. J Antimicrob Chemother. 2005 Apr;55(4):410-2. doi: 10.1093/jac/dki038. Epub 2005 Feb 22.

  PMID: 15728140 BACKGROUND

• Pomerantz RJ. Reservoirs, sanctuaries, and residual disease: the hiding spots of HIV-1. HIV Clin Trials. 2003 Mar-Apr;4(2):137-43. doi: 10.1310/80jh-148k-nadq-u927.

  PMID: 12671782 BACKGROUND

• Sedaghat AR, Siliciano JD, Brennan TP, Wilke CO, Siliciano RF. Limits on replenishment of the resting CD4+ T cell reservoir for HIV in patients on HAART. PLoS Pathog. 2007 Aug 31;3(8):e122. doi: 10.1371/journal.ppat.0030122.

  PMID: 17784786 BACKGROUND

• Siliciano JD, Siliciano RF. A long-term latent reservoir for HIV-1: discovery and clinical implications. J Antimicrob Chemother. 2004 Jul;54(1):6-9. doi: 10.1093/jac/dkh292. Epub 2004 May 26.

  PMID: 15163657 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, white cells, and whole blood

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Richard T. D'Aquila, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

• Carey K. Hwang, MD, PhD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Vanderbilt University

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 28, 2007
• Study Start: January 1, 2007
• Study Completion: January 1, 2011
• Last Updated: May 4, 2012

Record last verified: 2012-05

Locations

US (1)