HIV Viral Load Monitoring in Resource-Poor Settings
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.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Health Services Research
|Official Title:||Effectiveness of HIV Viral Load Monitoring of Patient Outcome in Resource-Poor Settings|
- Patient survival [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- To assess HIV clinical disease progression (weight, CD4 cell response, incident opportunistic infections) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- To assess the impact of more rapid ART regimen switching on available second and third-line treatment options [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- To monitor the effectiveness of newer antiretroviral medications introduced in Zambia (principally tenofovir) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- To characterize the timing and sequence of HIV drug resistance development among patients in each study arm [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
|Study Start Date:||December 2006|
|Estimated Study Completion Date:||June 2014|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
No Intervention: Standard of care
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.
Experimental: Routine HIV-1 viral load 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.
Other: HIV-1 viral load testing
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.
Other Name: Viral load measured by the Roche Amplicor HIV-1 RNA Monitor kit (version 1.5; Roche Molecular Diagnostics, Pleasanton, CA, USA).
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).
|Centre for Infectious Disease Research in Zambia|
|Principal Investigator:||Michael S. Saag, M.D.||University of Alabama at Birmingham|