Reaching 90% HIV Suppression: The Role of POC Viral Load Monitoring in Nigeria

Study Overview
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Brief Summary
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The UNAIDS 90-90-90 goals represents an ambitious strategy to end the acquired immunodeficiency syndrome (AIDS) epidemic by 2020 [UNAIDS, 2015]. While viral load (VL) quantification is the gold standard of HIV treatment monitoring, it is only routinely available and employed in resource-rich countries. The use of an affordable, reliable, point-of-care (POC) VL assay has been considered a game-changer, where increased access, minimal lab worker training, and same day results could be addressed in a single solution. To date, POC VL assays have been evaluated by their manufacturers with reference panels of samples with some in-country laboratory evaluations. While these are appropriate and critical first steps, it is also important to evaluate the impact of this new technology against the standard of care (SOC) method of VL monitoring in an actual resource-limited setting. Nigeria has the second highest burden of HIV in the world, with an estimated 3.2 million infected and serves as a relevant setting for testing feasibility and efficacy of POC VL monitoring [UNAIDS, 2016]. In order to present the case for implementing the use of POC VL testing across Nigeria, data on the acceptability, feasibility and efficacy of using POC testing for VL monitoring are needed. To address this need, the investigators have designed a randomized controlled trial comparing POC VL to monitoring to the SOC, which follows the Nigerian National Guidelines, to provide operational evidence for implementation of POC VL testing in Nigeria. This trial is aimed at testing the hypothesis that using POC versus SOC VL monitoring in HIV-infected patients newly initiating ART will improve overall ART outcomes, increase ART adherence and program retention rates, and result in faster switches to second-line treatment of patients failing first-line ART.

Detailed Description
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The investigators will conduct an un-blinded randomized implementation trial comparing POC VL monitoring, using the Cepheid Gene Xpert HIV-1 VL®, to SOC VL monitoring, using the Roche AmpliPrep/COBAS Taqman system. The trial will be conducted at two sites in Plateau State, Nigeria. ART-naïve patients initiating ART will be randomized on a 1:1 basis to the SOC VL monitoring control arm or the POC VL monitoring arm. VL monitoring will occur according to the current Nigerian ART guidelines-recommended algorithm, with the addition of a baseline VL test. For the month 6 and 12 visits, patients that are enrolled in the POC VL monitoring arm will be provided their VL results. Participants in the SOC arm will receive their Roche VL test results after the results become available per SOC protocol. All other aspects of their HIV care and treatment will be identical to services that they would normally receive at these treatment centers. The investigators will follow all patients up through their Month 12 follow-up visit. At trial exit, the investigators will ask patients, caregivers of patients under the age of 18 years, and providers for their participation in surveys on the operational performance and acceptability of the POC versus SOC VL monitoring. Following that time point, the patients will continue receiving HIV care and treatment utilizing the SOC procedures for the clinic.

Official Title
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Reaching 90% Target of HIV Viral Suppression: The Role of Point-of-Care Viral Load Monitoring in Resource-Constrained Settings in Nigeria

Conditions
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HIV/AIDS

Intervention / Treatment
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* Diagnostic Test: Point-of-care viral load monitoring test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -All HIV-infected patients newly initiating ART Exclusion Criteria: Previous ARV experience Pregnant
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized to have their viral load monitored by either the standard of care or point-of-care method at their follow-up clinical visits up to 12 months.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of Care (SOC)<br>Patients in this arm will have their viral load monitored using the standard of care method, using the Roche Cobas TaqMan HIV-1® v2 (Roche) assay. | |
| Experimental: Point-of-care (POC)<br>Patients in this arm will have their follow-up viral loads (after baseline) monitored using a Point-of-care viral load monitoring test, the Cepheid Xpert HIV-1 Viral Load assay. | Diagnostic Test: Point-of-care viral load monitoring test<br>* For enumerating viral load for patients in the POC arm, we will use the Cepheid Xpert® HIV-1 Viral Load test, a quantitative assay with a quantification range of 40 to 10,000,000 copies/mL. Based on the GeneXpert® technology, Xpert HIV-1 VL automates the test process, including RNA extraction, purification, reverse transcription and cDNA real-time quantitation in one fully integrated cartridge. The pre-loaded disposable single-use cartridges provide a visual read-out within 90 minutes. The assay requires 1 mL of plasma using a precision pipette (1.2 mL using a transfer pipette).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with VL<1000 copies/mL at month 12 post-initiation of ART (range 11-15 months) in SOC VL versus POC VL | Proportion of patients that have undetectable viral load at the end of observation (month 12) will be compared by treatment arm | 12 months (range 11-15 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in ART adherence patterns in patients in the SOC versus POC VL arms | Average percent adherence will be computed using patient refill data that are stored electronically. The average will be calculated as number of days supplied over total days in the given time interval, adjusting for amount of medication that should remain since last refill, computed based on amount supplied during the previous visit minus the number of days since the last visit. | From ART initiation to month 12 | 
| Difference in loss to follow-up rates by 12 months post-initiation of ART between patients monitored with SOC versus POC VL arms | LTFU at month 12 is defined as not having made any refill pick-ups or clinical visits since 9-month post-initiation of ART. | Month 12 | 
| Impact of trial site on differences in virologic suppression rates within patients receiving SOC VL monitoring | Comparison of data from two different trial sites | Month 12 | 
| Difference in time from ART initiation to the confirmation of virologic failure in SOC versus POC VL monitoring arms | Subset analysis in those that experienced virologic failure (confirmed) | ART Initiation to Month 12 | 
| Difference in time from ART initiation to switch to 2L treatment in patients in VF in SOC versus POC VL monitoring arms | Subset analysis in those that experienced virologic failure (confirmed) | ART Initiation to Month 12 | 
| Difference in time from specimen collection to availability of VL results in patient charts in SOC versus POC VL monitoring arms | Comparison of time from specimen collection to the time the result is entered into the patient chart by treatment arm | All follow-up visits at which VL monitored up to Month 12 | 
| Difference in time from specimen collection to delivery of VL results to patient in SOC versus POC VL monitoring arms | Comparison of time from specimen collection to the time the result is verbally conveyed to the patient by their clinician by treatment arm | All follow-up visits at which VL monitored up to Month 12 | 
| Difference in time from lab confirmation of first unsuppressed VL to adherence counseling provided and switch to 2L in SOC versus POC VL monitoring arms | Subset analysis in those that experienced virologic failure (confirmed) | All follow-up visits at which VL monitored up to Month 12 | 
| Difference in HIV DRM patterns in patients failing 1L ART in the SOC versus POC VL monitoring arm | Subset analysis in those that experienced virologic failure (confirmed) | Month 12 | 
| Health care worker (HCW) satisfaction level with POC versus SOC VL monitoring | Health care workers will complete a standardized survey querying about their satisfaction with the POC assay. The survey uses a scale measuring agreement level. The scale ranges from 0 to 5 where 0=not applicable, 1=strongly disagree and 5=strongly agree | Month 12 | 
| POC VL arm patient satisfaction with POC vs SOC VL testing | POC VL arm patients will be queried using a standardized survey about their satisfaction with the POC VL assay. The survey uses a scale measuring agreement level. The scale ranges from 0 to 5 where 0=not applicable, 1=strongly disagree and 5=strongly agree. | Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Point-of-care, Viral load monitoring, Nigeria