The VMVN Study: Virological Monitoring in Viet Nam

Study Overview
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Brief Summary
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The purpose of the study is to test the hypothesis that the addition of routine viral load testing to the standard laboratory monitoring of HIV patients on first-line antiretroviral treatment (ART) in Vietnam will result in better clinical outcomes for patients.

Detailed Description
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The optimal strategy for monitoring antiretroviral therapy (ART) in resource-limited settings (RLS) is unknown. In developed countries, routine monitoring with CD4 count and viral load (VL) testing is standard practice. In RLS, however, limitations in the availability of the technology for VL testing, and in financial resources to pay for VL testing, mean that few developing countries provide VL testing as part of the routine monitoring of patients on ART. Instead, ART is monitored primary by clinical examination with CD4 testing where available. This strategy has been endorsed by the most recent WHO guidelines for ART (WHO, 2010). Standard laboratory monitoring of patients on ART in Vietnam includes CD4 testing every 6 months, where available. In many rural areas of the country, CD4 testing is not available and only clinical monitoring is used. In this study we will test the hypothesis that routine viral monitoring every 6 months for patients on first-line ART will result in significantly higher rates of virological suppression and decrease the incidence of death or new or recurrent AIDS-defining illnesses by 50% within three years.

Official Title
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Effect of Routine Viral Load Monitoring on Clinical and Immunological Outcomes and Antiretroviral Drug Resistance on Patients Taking First-line Antiretroviral Drugs in Vietnam

Conditions
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HIV Infection, AIDS

Intervention / Treatment
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* Other: Standard Care
* Other: Virological Monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 Confirmed HIV infection Not currently taking ART Meets Vietnam MOH criteria for ART (THROUGH OCTOBER 2011:CD4<250 cells/mm3, WHO Clinical Stage IV, or WHO clinical stage III with CD4<350 cells/mm3; FROM NOVEMBER 2011: CD4<350 cells/mm3, OR WHO Clinical Stage III or IV) Completes required Vietnam MOH ART adherence training Signs written informed consent form Exclusion Criteria: Any ART use within the previous 3 months History of treatment failure on first-line ART or known resistance to first-line ART. Unable or unwilling to give written informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Standard Monitoring<br>The patients in the standard monitoring arm will receive routine laboratory monitoring as provided to all patients in public HIV clinics in Vietnam, including CD4 count, complete blood count, and liver functions tests every 6 months. | Other: Standard Care<br>* CD4, liver function and CBC every 6 months<br>|
| Active Comparator: Virological Monitoring<br>The patients in the virological monitoring arm will have routine laboratory monitoring as in the standard monitoring arm and in addition will have a viral load test performed every 6 months while in treatment. The first test will be done 6 months after initiating ART. | Other: Virological Monitoring<br>* Viral Load test every 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death or new/recurrent AIDS-Defining (WHO Clinical Stage IV) Illnesses | The number of deaths and/or new/recurrent WHO Clinical Stage IV clinical illnesses that occur over 3 years of follow-up in each group. | 3 years | 
| Virological Suppression | The percentage of patients in each group who are still on treatment at 3 years who have virological suppression, defined as an HIV viral load below the level of laboratory detection. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to identification and diagnosis of treatment failure. | To calculate the difference in times in the 2 groups from the first emergence of active viral replication (defined as a detectable viral load) to identification and diagnosis of treatment failure. | 3 years | 
| Time from virological treatment failure to switch to second line ART. | We will calculate the mean time from virological treatment failure to switch to second line ART in both groups. | 3 years | 
| Resistance mutations | The difference in resistance mutation patterns at the diagnosis of virological treatment failure in each group. | 3 years | 
| Sensitivity and specificity of WHO criteria for treatment failure | To determine the sensitivity and specificity of WHO criteria for treatment failure among patients on first-line ARV in Vietnam. | 3 years | 
| Cost-benefit analysis | To evaluate and compare the costs and benefits of adding routine VL testing to standard laboratory monitoring for patients on first-line ART in Vietnam. In the event that the trial shows a benefit in the primary outcome of decreased number of deaths plus WHO Stage 4 clinical events, the analysis will evaluate the cost per life saved and the cost per outcome event avoided. The analysis will also include a cost per quality-adjusted life year saved. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ART, antiretroviral, treatment, Vietnam, Asia, viral load