NCT00929604

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,112

participants targeted

Target at P75+ for not_applicable hiv

Timeline
Completed

Started Dec 2006

Longer than P75 for not_applicable hiv

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2006

Completed
2.6 years until next milestone

First Submitted

Initial submission to the registry

June 25, 2009

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 29, 2009

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2012

Completed
2.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2014

Completed
Last Updated

October 9, 2014

Status Verified

October 1, 2014

Enrollment Period

5.4 years

First QC Date

June 25, 2009

Last Update Submit

October 8, 2014

Conditions

Keywords

HIVAIDSZambiaviral loadantiretroviral therapycluster randomizationART monitoringtreatment failurerandomized clinical trialtreatment naive

Outcome Measures

Primary Outcomes (1)

  • Patient survival

    36 months

Secondary Outcomes (5)

  • To assess HIV clinical disease progression (weight, CD4 cell response, incident opportunistic infections)

    36 months

  • To assess the impact of more rapid ART regimen switching on available second and third-line treatment options

    36 months

  • To monitor the effectiveness of newer antiretroviral medications introduced in Zambia (principally tenofovir)

    36 months

  • To characterize the timing and sequence of HIV drug resistance development among patients in each study arm

    36 months

  • To assess the feasibility, acceptability, and cost effectiveness of the two management strategies in a resource-constrained sub-Saharan African setting

    36 months

Study Arms (2)

Standard of care

NO INTERVENTION

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 HIV-1 viral load testing

EXPERIMENTAL

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.

Other: HIV-1 viral load testing

Interventions

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.

Also known as: Viral load measured by the Roche Amplicor HIV-1 RNA Monitor kit (version 1.5; Roche Molecular Diagnostics, Pleasanton, CA, USA).
Routine HIV-1 viral load testing

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Centre for Infectious Disease Research in Zambia

Lusaka, Zambia

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Acquired Immunodeficiency SyndromeHIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Study Officials

  • Michael S. Saag, M.D.

    University of Alabama at Birmingham

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
HEALTH SERVICES RESEARCH
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 25, 2009

First Posted

June 29, 2009

Study Start

December 1, 2006

Primary Completion

May 1, 2012

Study Completion

June 1, 2014

Last Updated

October 9, 2014

Record last verified: 2014-10

Locations