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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Mbarara University Joint Programme, Makerere University
Infectious Disease Research Collaboration
Makerere University
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01479634
First received: November 22, 2011
Last updated: October 9, 2013
Last verified: October 2013
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Early Antiretroviral Therapy in Resource Limited Settings in Patients With High CD4+ Cell Counts

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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    Proportion of total medication doses taken by patients at 48 weeks, assessed by pharmacy refill records, stratified by study arm.


Estimated Enrollment: 400
Study Start Date: October 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 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] OR
  3. Ritonavir/Lopinavir [RTV/LPV] fixed dose combination
Other Names:
  • 1) FTC/TDF
  • 2) Sustiva®
  • 3) Kaletra®, Aluvia®

Detailed Description:

After dramatic progress in recent years, HIV care for patients in resource limited settings stands at a crossroads. 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. 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.

We propose here 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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]

  • Female participants of reproductive potential must have a negative urine or serum pregnancy test performed within 7 days prior to screen date. The term "female participants of reproductive potential" is defined as women who meet all three of the following criteria:

    • have reached menarche
    • have had menses within the preceding 24 months
    • have not undergone a surgical procedure that would preclude pregnancy (defined as hysterectomy, bilateral oophorectomy and/or salpingotomy).
  • Female participants in Arm B who are participating in sexual activity that could lead to pregnancy must agree to use at least one reliable method of contraception while receiving EFV, and for 6 weeks after stopping this drug. Reliable method is defined here as either an intrauterine device (IUD) or hormonal-based contraception (either pill-based or injectable). All participants will be encouraged to use a second form of contraception including but not limited to condoms.

Female participants in Arm B who choose not to or are unable to use contraception during the study will not be eligible to receive EFV, and will instead receive RTV/LPV (Kaletra®).

  • 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® or Kaletra®.
  • Active World Health Organization (WHO) HIV stage 3 or 4 illness
  • Pregnancy.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01479634

Locations
Uganda
Bwizibwera Level IV Health Center
Bwizibwera, Mbarara district, Uganda
Sponsors and Collaborators
University of California, San Francisco
Mbarara University Joint Programme, Makerere University
Infectious Disease Research Collaboration
Makerere University
Investigators
Study Chair: Diane Havlir, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01479634     History of Changes
Other Study ID Numbers: EARLI
Study First Received: November 22, 2011
Last Updated: October 9, 2013
Health Authority: Uganda: National Council for Science and Technology
Uganda: National Drug Authority
Uganda: Research Ethics Committee
United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
HIV
ART

ClinicalTrials.gov processed this record on July 10, 2014