HIVEARLINCT01479634
Early HIV Therapy in Patients With High CD4 Cell Counts
A study testing Standard ART and Study-Provided ART in people with HIV, run by University of California, San Francisco at 1 site in Uganda.
Trial summary
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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV
- What is being tested?
- Standard ART and Study-Provided ART
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 279 participants
- Where
- 1 siteUganda
- Study dates
- Oct 2011to Jun 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Early Antiretroviral Therapy in Resource Limited Settings in Patients With High CD4+ Cell Counts (EARLI)
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
Read the 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:
- 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.
- To evaluate the programmatic costs of streamlined ART delivery to asymptomatic high CD4+ count individuals.
Secondary Objectives:
- To evaluate the 96 week efficacy of ART initiated in high CD4+ cell count individuals.
- To identify predictors of retention in care among high CD4+ cell count ART initiators.
- To assess adverse events among high CD4+ cell count ART initiators.
- To assess medication adherence among high CD4+ cell count ART initiators.
- Conditions
- HIV
- Being tested
- Standard ART, Study-Provided ART
- Keywords
- HIV, ART
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard ARTDrug
Standard Ugandan 3-drug antiretroviral therapy regimen consistent with current practices
Study-Provided ARTDrug
Also called 1) FTC/TDF, 2) Sustiva®
Study provided drugs:
- Truvada® (one tablet PO daily of fixed dose combination consisting of tenofovir disoproxyl fumarate [TDF] and emtricitabine [FTC]) PLUS
- Efavirenz [EFV]
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Active comparator | Treatment for HIV in participants with CD4+ cell counts 250-350 cells/uL Receives: Drug: Standard ART |
| Arm B | Active comparator | Treatment for HIV in participants with CD4+ cell counts >350 cells/uL Receives: Drug: Study-Provided ART |
What is being measured
The primary outcome is the main question the study is designed to answer.
48-Week Efficacy
Proportion of patients with virologic suppression (HIV-1 plasma RNA ≤400 copies/cc) at 48 weeks, stratified by study arm.
Measured: When all participants reach 48 weeks on study
Programmatic Costs
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
Measured: When all participants reach 48 weeks on study
Secondary outcomes (4)
96-Week and 144-Week Efficacy
Proportion of patients with virologic suppression (HIV-1 plasma RNA ≤400 copies/cc) at 96 and 144 weeks, stratified by study arm.
Measured: When all particiants reach 96 and 144 weeks on study, respectively
Predictors of Retention in Care
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.
Measured: When all participants reach 48 weeks on study, then again 144 weeks on study
Adverse Event Rates
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.
Measured: When all participants reach 48 weeks on study, then again at 144 weeks
Medication Adherence
Proportion of total medication doses taken by patients at 48 weeks, assessed by pharmacy refill records, stratified by study arm.
Measured: When all participants reach 48 weeks on study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2011 (estimated)
- Study startOct 2011
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 279 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Makerere University Joint AIDS Program, Infectious Diseases Research Collaboration, Uganda, Makerere University
- Responsible party
- Sponsor
- Investigators
- Diane Havlir, MD, Study chair, University of California, San Francisco, San Francisco, CA, USAVivek Jain, MD, Principal investigator, University of California, San Francisco, San Francisco, CA, USAMoses Kamya, MBChB, MMed, PhD, Principal investigator, Makerere University School of Medicine, Kampala, Uganda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01479634
- Sponsor's protocol ID
- EARLI
- Acronym
- EARLI
- Status last verified
- Mar 2016
- First submitted
- 22 Nov 2011
- Last updated
- 4 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Jain V, Byonanebye DM, Amanyire G, Kwarisiima D, Black D, Kabami J, Chamie G, Clark TD, Rooney JF, Charlebois ED, Kamya MR, Havlir DV; SEARCH Collaboration. Successful antiretroviral therapy delivery and retention in care among asymptomatic individuals with high CD4+ T-cell counts above 350 cells/mul in rural Uganda. AIDS. 2014 Sep 24;28(15):2241-9. doi: 10.1097/QAD.0000000000000401.
PubMed 25022596Jain V, Chang W, Byonanebye DM, Owaraganise A, Twinomuhwezi E, Amanyire G, Black D, Marseille E, Kamya MR, Havlir DV, Kahn JG. Estimated Costs for Delivery of HIV Antiretroviral Therapy to Individuals with CD4+ T-Cell Counts >350 cells/uL in Rural Uganda. PLoS One. 2015 Dec 3;10(12):e0143433. doi: 10.1371/journal.pone.0143433. eCollection 2015.
PubMed 26632823
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Antiretroviral Therapy in Resource Limited Settings in Patients With High CD4+ Cell Counts (EARLI)
- ClinicalTrials.gov ID
- NCT01479634
- Acronym / sponsor ID
- EARLI / EARLI
- Conditions
- HIV
- Keywords
- HIV, ART
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 279 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Makerere University Joint AIDS Program, Infectious Diseases Research Collaboration, Uganda, Makerere University
- Study start
- Oct 2011
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 24 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- 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.
- To evaluate the programmatic costs of streamlined ART delivery to asymptomatic high CD4+ count individuals.
Secondary Objectives:
- To evaluate the 96 week efficacy of ART initiated in high CD4+ cell count individuals.
- To identify predictors of retention in care among high CD4+ cell count ART initiators.
- To assess adverse events among high CD4+ cell count ART initiators.
- To assess medication adherence among high CD4+ cell count ART initiators.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Active comparator | Drug: Standard ARTTreatment for HIV in participants with CD4+ cell counts 250-350 cells/uL |
| Arm B | Active comparator | Drug: Study-Provided ARTTreatment for HIV in participants with CD4+ cell counts >350 cells/uL |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard ARTStandard Ugandan 3-drug antiretroviral therapy regimen consistent with current practices | Drug | Arm A |
| Study-Provided ARTAlso: 1) FTC/TDF, 2) Sustiva®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] | Drug | Arm B |
Primary outcome
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
4 secondary outcomes
96-Week and 144-Week Efficacy
Time frame: When all particiants reach 96 and 144 weeks on study, respectively
Predictors of Retention in Care
Time frame: When all participants reach 48 weeks on study, then again 144 weeks on study
Adverse Event Rates
Time frame: When all participants reach 48 weeks on study, then again at 144 weeks
Medication Adherence
Time frame: When all participants reach 48 weeks on study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2016.
- Results publication: PubMed 25022596Jain V, Byonanebye DM, Amanyire G, Kwarisiima D, Black D, Kabami J, Chamie G, Clark TD, Rooney JF, Charlebois ED, Kamya MR, Havlir DV; SEARCH Collaboration. Successful antiretroviral therapy delivery and retention in care among asymptomatic individuals with high CD4+ T-cell counts above 350 cells/mul in rural Uganda. AIDS. 2014 Sep 24;28(15):2241-9. doi: 10.1097/QAD.0000000000000401.
- Derived from this study: PubMed 26632823Jain V, Chang W, Byonanebye DM, Owaraganise A, Twinomuhwezi E, Amanyire G, Black D, Marseille E, Kamya MR, Havlir DV, Kahn JG. Estimated Costs for Delivery of HIV Antiretroviral Therapy to Individuals with CD4+ T-Cell Counts >350 cells/uL in Rural Uganda. PLoS One. 2015 Dec 3;10(12):e0143433. doi: 10.1371/journal.pone.0143433. eCollection 2015.
- MU-UCSF Research Collaboration websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Diane Havlir, MD study chair
University of California, San Francisco, San Francisco, CA, USA
Vivek Jain, MD principal investigator
University of California, San Francisco, San Francisco, CA, USA
Moses Kamya, MBChB, MMed, PhD principal investigator
Makerere University School of Medicine, Kampala, Uganda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standard ART and Study-Provided ART in people with HIV, run by University of California, San Francisco at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
48-Week Efficacy (time frame: When all participants reach 48 weeks on study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01479634, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2016.