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Early HIV Therapy in Patients With High CD4 Cell Counts (EARLI)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01479634
First Posted: November 24, 2011
Last Update Posted: March 4, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Makerere University Joint AIDS Program
Infectious Diseases Research Collaboration, Uganda
Makerere University
Information provided by (Responsible Party):
University of California, San Francisco
  Purpose
A study of antiretroviral therapy (ART) initiation under a "streamlined model of care" in HIV-positive patients with CD4+ cell counts greater ≥ 250 cells/uL

Condition Intervention
HIV Drug: Standard ART Drug: Study-Provided ART

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Early Antiretroviral Therapy in Resource Limited Settings in Patients With High CD4+ Cell Counts (EARLI)

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • 48-Week Efficacy [ Time Frame: When all participants reach 48 weeks on study ]
    Proportion of patients with virologic suppression (HIV-1 plasma RNA ≤400 copies/cc) at 48 weeks, stratified by study arm.

  • Programmatic Costs [ Time Frame: When all participants reach 48 weeks on study ]
    Total estimated costs of provider time, medications, diagnostic testing, and healthcare facility infrastructure per patient treated with ART for one year, stratified by study arm


Secondary Outcome Measures:
  • 96-Week and 144-Week Efficacy [ Time Frame: When all particiants reach 96 and 144 weeks on study, respectively ]
    Proportion of patients with virologic suppression (HIV-1 plasma RNA ≤400 copies/cc) at 96 and 144 weeks, stratified by study arm.

  • Predictors of Retention in Care [ Time Frame: When all participants reach 48 weeks on study, then again 144 weeks on study ]
    Factors statistically significantly associated with attendance at all scheduled clinical visits throughout the first 48 weeks of ART, and throughout the full 144 week study period, stratified by study arm.

  • Adverse Event Rates [ Time Frame: When all participants reach 48 weeks on study, then again at 144 weeks ]
    Describe grade 3 or 4 toxicities (defined by NIH DAIDS scale) that occur throughout the first 48 weeks of ART, and throughout the full 144 week study period, stratified by study arm. These will be assessed by active and passive ascertainment and clinical verification, stratified by study arm.

  • Medication Adherence [ Time Frame: When all participants reach 48 weeks on study ]
    Proportion of total medication doses taken by patients at 48 weeks, assessed by pharmacy refill records, stratified by study arm.


Enrollment: 279
Study Start Date: October 2011
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
Treatment for HIV in participants with CD4+ cell counts 250-350 cells/uL
Drug: Standard ART
Standard Ugandan 3-drug antiretroviral therapy regimen consistent with current practices
Active Comparator: Arm B
Treatment for HIV in participants with CD4+ cell counts >350 cells/uL
Drug: Study-Provided ART

Study provided drugs:

  1. Truvada® (one tablet PO daily of fixed dose combination consisting of tenofovir disoproxyl fumarate [TDF] and emtricitabine [FTC]) PLUS
  2. Efavirenz [EFV]
Other Names:
  • 1) FTC/TDF
  • 2) Sustiva®

Detailed Description:

After dramatic progress in recent years, HIV care for patients in resource limited settings is rapidly evolving to newer models of care delivery. Governments, non-governmental organizations and charitable foundations are placing increasing scrutiny on the programmatic costs associated with delivering antiretroviral therapy (ART). Given these realities, if the global ART roll-out is to continue successfully, we must develop innovative new ways of providing HIV care and ART that are more efficient, more cost-effective, and tightly integrated within country-level health systems. We must treat more patients with fewer resources, and we need sustainable simple models for ART delivery.

These goals can be accomplished building on several existing knowledge points. First, initiating ART at earlier disease stages and at higher CD4+ cell counts may prevent irreversible immunologic damage, prevent opportunistic infections and non-AIDS-associated morbidities, and may prevent death. International and national HIV policy bodies have increasingly recognized this and adjusted recommendations in this direction. Second, ART initiation at higher CD4+ cell counts is less complex, triggers fewer complications, and is less costly to healthcare systems. Third, patients responding to therapy and doing well require fewer physician-administered follow-up visits. This can allow for "task-shifting" to non-MD providers, and the establishment of tiered healthcare delivery down the spectrum of medical acuity. Fourth, the lack of viral load monitoring is responsible for major structural problems in how we deliver ART, causing delays in recognizing ART failure, preventing clinicians from diagnosing HIV drug resistance, and making the decision to switch a patient to a new ART regimen very error-prone.

The EARLI study is a pilot study that will address and investigate all of the above critical issues. This study will focus exclusively on asymptomatic patients with CD4 cell counts ≥250 cells/uL. These relatively healthier individuals are well suited to a more streamlined approach to ART delivery and healthcare provision.

Primary Objectives:

A. To evaluate the 48 week efficacy of ART initiated in asymptomatic individuals with high CD4+ cell counts (CD4+ > 250 cells/uL) and provided in a "streamlined" mode of care.

B. To evaluate the programmatic costs of streamlined ART delivery to asymptomatic high CD4+ count individuals.

Secondary Objectives:

A. To evaluate the 96 week efficacy of ART initiated in high CD4+ cell count individuals.

B. To identify predictors of retention in care among high CD4+ cell count ART initiators.

C. To assess adverse events among high CD4+ cell count ART initiators.

D. To assess medication adherence among high CD4+ cell count ART initiators.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection diagnosed by a rapid HIV test or any licensed ELISA test kit and documented in the participant's medical chart and re-verified at the time of study screening (hereafter: "screen date").
  • Most recent CD4+ cell count ≥ 250 cells/uL:

Arm A: CD4+ cell count 250-350 cells/uL Arm B: CD4+ cell count >350 cells/uL

  • Age ≥ 18 years.
  • Residence within a 30 kilometer radius of the Bwizibwera HC-IV.
  • Willing to initiate ART if the CD4+ cell count is ≥ 350 cells/uL.
  • The following laboratory values obtained at the screening visit:

    • Absolute neutrophil count (ANC) ≥ 500 cells/uL
    • Hemoglobin ≥ 7.0 g/dL
    • Platelet count ≥ 50,000/uL
    • ALT (SGPT) ≤ 5 times greater than the upper limit of normal
    • Estimated glomerular filtration rate (eGFR) of ≥ 60 mL/minute by the Modification of Diet in Renal Disease (MDRD) formula:

eGFR = 186 * Serum creatinine-1.154 * Age-0.203 * [1.21 if African] * [0.742 if female]

  • Ability to swallow oral medications.
  • Ability and willingness of participant to give informed written consent.

Exclusion Criteria:

  • Receipt at any time prior to study entry of > 7 days cumulative treatment with any ARV or combination of ARVs, except ARVs taken for any length of time during pregnancy for the prevention of mother to child transmission (pMTCT) or ARVs taken for occupational exposure.
  • For Arm B participants only: allergy/sensitivity to TDF, FTC, EFV, RTV, LPV or formulations of any of these three medications, or to co-formulated Truvada®.
  • Active World Health Organization (WHO) HIV stage 3 or 4 illness
  • Pregnancy.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01479634


Locations
Uganda
Bwizibwera Level IV Health Center
Bwizibwera, Mbarara district, Uganda
Sponsors and Collaborators
University of California, San Francisco
Makerere University Joint AIDS Program
Infectious Diseases Research Collaboration, Uganda
Makerere University
Investigators
Study Chair: Diane Havlir, MD University of California, San Francisco, San Francisco, CA, USA
Principal Investigator: Vivek Jain, MD University of California, San Francisco, San Francisco, CA, USA
Principal Investigator: Moses Kamya, MBChB, MMed, PhD Makerere University School of Medicine, Kampala, Uganda