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HIV Viral Load Monitoring in Resource-Poor Settings

Primary Purpose

HIV, AIDS, HIV Infections

Status
Completed
Phase
Not Applicable
Locations
Zambia
Study Type
Interventional
Intervention
HIV-1 viral load testing
Sponsored by
University of Alabama at Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for HIV focused on measuring HIV, AIDS, Zambia, viral load, antiretroviral therapy, cluster randomization, ART monitoring, treatment failure, randomized clinical trial, treatment naive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Documented HIV-1 infection (according to local standard rapid testing algorithms)
  • Age 18 years or greater
  • Able and willing to provide informed consent to participate

  • Eligible for antiretroviral therapy per Zambian national guidelines, which are any of the following:

    • CD4+ cell count less than 200 cells/mm3;
    • WHO Stage IV disease; or
    • WHO Stage III disease and CD4+ cell count less than 350 cells/mm3
  • Residence in the geographical catchment area of the VLS clinic and intent to remain there for the duration of the study
  • Willingness to adhere to the study visit schedule and to be followed-up at home in the event of a missed study visit
  • Initiating ART on the day of VLS enrollment, informed consent, and baseline blood collection

Exclusion Criteria:

  • Receipt of more than 7 days (cumulative) of prior antiretroviral therapy at any time prior to study entry, with the exception of zidovudine and/or single dose nevirapine for prevention of mother-to-child transmission;
  • Any exposure to antiretroviral therapy in the past one month
  • A condition that, in the opinion of the investigators, would interfere with adherence to study requirements (e.g., mental illness or active drug or alcohol use or dependence)
  • Serious illness requiring referral to hospital at the time of ART initiation
  • For patients seeking care at sites randomized to the standard of care arm: participation in another research protocol that offers routine viral load testing
  • Unwillingness to consent to all aspects of study protocol including blood specimen storage

Sites / Locations

  • Centre for Infectious Disease Research in Zambia

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Standard of care

Routine HIV-1 viral load testing

Arm Description

Standard of care arm: utilizes the current standard of care per Zambian national guidelines to determine treatment failure and eligibility for second-line ART. HIV-1 viral load measurement is performed if the criteria for either immunologic (i.e., CD4+ lymphocyte count-based) or clinical treatment failure are fulfilled. If both immunologic and clinical treatment failure criteria are fulfilled, the ART regimen is changed to second-line without VL testing.

Routine viral load testing arm: Routine HIV viral load testing at ART initiation (baseline) and at 3, 6, 12, 18, 24, 30 and 36 months thereafter.

Outcomes

Primary Outcome Measures

Patient survival

Secondary Outcome Measures

To assess HIV clinical disease progression (weight, CD4 cell response, incident opportunistic infections)
To assess the impact of more rapid ART regimen switching on available second and third-line treatment options
To monitor the effectiveness of newer antiretroviral medications introduced in Zambia (principally tenofovir)
To characterize the timing and sequence of HIV drug resistance development among patients in each study arm
To assess the feasibility, acceptability, and cost effectiveness of the two management strategies in a resource-constrained sub-Saharan African setting

Full Information

First Posted
June 25, 2009
Last Updated
October 8, 2014
Sponsor
University of Alabama at Birmingham
Collaborators
Adult AIDS Clinical Trials Group
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1. Study Identification

Unique Protocol Identification Number
NCT00929604
Brief Title
HIV Viral Load Monitoring in Resource-Poor Settings
Official Title
Effectiveness of HIV Viral Load Monitoring of Patient Outcome in Resource-Poor Settings
Study Type
Interventional

2. Study Status

Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Alabama at Birmingham
Collaborators
Adult AIDS Clinical Trials Group

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
No randomized clinical trial to date has demonstrated a survival benefit of using regular HIV-1 ribonucleic acid (RNA) viral load (VL) testing to monitor patients' responses to antiretroviral therapy (ART) for HIV infection. The measurement of VL is recommended to monitor the response to ART in developed countries. In resource-constrained settings, the World Health Organization (WHO) does not recommend routine VL testing, in part due to the cost and complex infrastructure needed for reliable results. In these settings, WHO has proposed the use of clinical and CD4+ lymphocyte-based criteria to guide treatment decisions. However, multiple studies have demonstrated the poor performance of these criteria in sub-Saharan Africa and the frequent discordance between immunologic and virologic responses to ART. The use of routine viral load monitoring should be evaluated in resource-constrained settings. The investigators hypothesize that routine viral load testing of patients on ART will improve patient survival, decrease disease progression and development of drug resistance, and will be feasible and cost-effective for resource-constrained settings.
Detailed Description
The study 'Effectiveness of HIV Viral Load Monitoring on Patient Outcome in Resource-Poor Settings,' is a dual-arm, cluster randomized trial to evaluate the use of routine plasma HIV-1 VL monitoring to improve survival and decrease HIV disease progression in patients receiving ART. The primary objective is to assess mortality at 36 months among ART naïve patients initiating therapy and receiving care at facilities with access to routine HIV VL testing (at ART initiation, at 3 months and at every 6 months thereafter) compared to those initiating first regimens and receiving care at facilities according to our local standard of care (which uses immunological [i.e. CD4+ lymphocyte count-based]and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV, AIDS, HIV Infections
Keywords
HIV, AIDS, Zambia, viral load, antiretroviral therapy, cluster randomization, ART monitoring, treatment failure, randomized clinical trial, treatment naive

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2112 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of care
Arm Type
No Intervention
Arm Description
Standard of care arm: utilizes the current standard of care per Zambian national guidelines to determine treatment failure and eligibility for second-line ART. HIV-1 viral load measurement is performed if the criteria for either immunologic (i.e., CD4+ lymphocyte count-based) or clinical treatment failure are fulfilled. If both immunologic and clinical treatment failure criteria are fulfilled, the ART regimen is changed to second-line without VL testing.
Arm Title
Routine HIV-1 viral load testing
Arm Type
Experimental
Arm Description
Routine viral load testing arm: Routine HIV viral load testing at ART initiation (baseline) and at 3, 6, 12, 18, 24, 30 and 36 months thereafter.
Intervention Type
Other
Intervention Name(s)
HIV-1 viral load testing
Other Intervention Name(s)
Viral load measured by the Roche Amplicor HIV-1 RNA Monitor kit (version 1.5; Roche Molecular Diagnostics, Pleasanton, CA, USA).
Intervention Description
Plasma HIV-1 RNA viral load testing performed at ART initiation (baseline) and at 3, 6, 12, 18, 24, 30, and 36 months thereafter. Routine viral load results are provided to clinicians for the management of the participant's HIV treatment.
Primary Outcome Measure Information:
Title
Patient survival
Time Frame
36 months
Secondary Outcome Measure Information:
Title
To assess HIV clinical disease progression (weight, CD4 cell response, incident opportunistic infections)
Time Frame
36 months
Title
To assess the impact of more rapid ART regimen switching on available second and third-line treatment options
Time Frame
36 months
Title
To monitor the effectiveness of newer antiretroviral medications introduced in Zambia (principally tenofovir)
Time Frame
36 months
Title
To characterize the timing and sequence of HIV drug resistance development among patients in each study arm
Time Frame
36 months
Title
To assess the feasibility, acceptability, and cost effectiveness of the two management strategies in a resource-constrained sub-Saharan African setting
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Documented HIV-1 infection (according to local standard rapid testing algorithms) Age 18 years or greater Able and willing to provide informed consent to participate Eligible for antiretroviral therapy per Zambian national guidelines, which are any of the following: CD4+ cell count less than 200 cells/mm3; WHO Stage IV disease; or WHO Stage III disease and CD4+ cell count less than 350 cells/mm3 Residence in the geographical catchment area of the VLS clinic and intent to remain there for the duration of the study Willingness to adhere to the study visit schedule and to be followed-up at home in the event of a missed study visit Initiating ART on the day of VLS enrollment, informed consent, and baseline blood collection Exclusion Criteria: Receipt of more than 7 days (cumulative) of prior antiretroviral therapy at any time prior to study entry, with the exception of zidovudine and/or single dose nevirapine for prevention of mother-to-child transmission; Any exposure to antiretroviral therapy in the past one month A condition that, in the opinion of the investigators, would interfere with adherence to study requirements (e.g., mental illness or active drug or alcohol use or dependence) Serious illness requiring referral to hospital at the time of ART initiation For patients seeking care at sites randomized to the standard of care arm: participation in another research protocol that offers routine viral load testing Unwillingness to consent to all aspects of study protocol including blood specimen storage
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael S. Saag, M.D.
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Infectious Disease Research in Zambia
City
Lusaka
Country
Zambia

12. IPD Sharing Statement

Citations:
PubMed Identifier
20300631
Citation
Koethe JR, Westfall AO, Luhanga DK, Clark GM, Goldman JD, Mulenga PL, Cantrell RA, Chi BH, Zulu I, Saag MS, Stringer JS. A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics. PLoS One. 2010 Mar 12;5(3):e9680. doi: 10.1371/journal.pone.0009680. Erratum In: PLoS One. 2010; 5(3) doi: 10.1371/annotation/dbc3ee9b-dab4-494b-87d1-7c32b8d684b5.
Results Reference
derived

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HIV Viral Load Monitoring in Resource-Poor Settings

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