INTERVAL: Varying Intervals of ART to Improve Outcomes in HIV

Study Overview
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Brief Summary
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This is an unblinded cluster-randomized study to evaluate the effectiveness of two strategies for scripting/dispensing of antiretroviral therapy (ART) on retention, virologic suppression, and cost compared to the standard of care. The study will be conducted in Malawi and Zambia among approximately 8,200 HIV-1-infected adults (18 years or older) who are stable on ART. Clusters will be randomized to one of three study arms: (1) standard of care (SOC) ART scripting (varies by country, region, clinic, and/or provider), (2) three-month ART scripting, and (3) six-month ART scripting. 30 clusters will be selected for the study, 15 in Malawi and 15 in Zambia, and will be randomized to a study arm.

Detailed Description
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This study will be conducted among approximately 8,200 HIV-infected individuals age 18 years or older who are stable on antiretroviral therapy (ART) in 30 clusters in Malawi and Zambia. Individuals will be screened at routine clinic visits and enrolled if they meet inclusion criteria. Enrolled individuals will receive standard of care at their site with the exception of their ART dispensing interval based on the assigned randomization. Outcomes will be assessed after 12 months, but all participants will be under observational follow-up for 36 months, with annual re-assessment of retention, virologic suppression, and cost-effectiveness. There will be no contact with study participants during the period of follow-up. Endpoints will be determined by chart review after the primary endpoint is reached (12 months). Endpoint data collection will include: Retention in care on strategy Suppressed viral load of <1,000 copies done as part of standard of care viral load monitoring In a subset of participants in Malawi (n=1,500), we will perform a review of participants' health passports, a record of patient clinic visits, general health information, and medications that is possessed by patients in Malawi, after the 12-month endpoint has been completed. Data will be collected on interim clinic visits, such as reason for visit/services received (sick, family planning, non-communicable disease treatment), frequency of visits, and location of clinic services. In a subset of participants ( 240), we will perform a post intervention study visit after the 12-month endpoint is completed. Qualitative interviews will be performed with a subset of participants and will focus on patient experience with assigned dispensing interval, including challenges/barriers and facilitators towards adherence and retention. Focused questions around endpoints (if default, reasons; if virologic failure, reasons including adherence) will also be addressed in the post-intervention visit.

Official Title
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INTERVAL: Varying Intervals of ART to Improve Outcomes in HIV

Conditions
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HIV-1-infection

Intervention / Treatment
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* Other: Three-month ART dispensing
* Other: Six-month ART dispensing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age. Willing and able to provide written informed consent for participation in this study. Confirmed HIV-1 infection based on country standard of care for testing. On antiretroviral treatment (ART) for at least six months. On a first-line ART regimen as defined by country-specific guidelines. No drug toxicity/tolerability issues with ART regimen within the prior six months. No period of more than one month without ART medication possession within the last six months. No active opportunistic infection suspected (including tuberculosis) and not treated for an opportunistic infection in the last 30 days. No active comorbidity (including hypertension) and not treated for a comorbidity in the last 30 days. No viral load of more than 1000 copies/ml (using standard assay) within the last six months. Not currently pregnant. At least six months postpartum if recently delivered a baby. Not currently breastfeeding or planning to breastfeed. Exclusion Criteria: Under 18 years of age. Viral load of 1000 copies/ml or greater (using standard assay) within the last six months. On alternative first-line or second-line ART regimen. One month or more without medication possession within the last six months. Experienced an ART toxicity/tolerability issue within the last six months. Currently receiving treatment for tuberculosis or receiving treatment for any other opportunistic infection or comorbidity (including hypertension). Pregnant or less than six months postpartum. Women who are breastfeeding. Unwilling or unable to provide informed consent. Previously enrolled in the study. Currently enrolled in any other research study at the site that involves adherence/retention or alters delivery of HIV care.

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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study will be a cluster randomized trial comparing three different antiretroviral therapy (ART) dispensing strategies. Clusters will be comprised of individual clinics in Malawi and Zambia. Enrolled individuals will receive standard of care at their site with the exception of the ART dispensing interval based on the assigned randomization. Outcomes will be assessed after 12 months.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of care ART dispensing<br>The standard of care arm will allow ART dispensing based on usual practice at the clinic. Standard of care is anticipated to have variability in how ART is dispensed, although the approach should be consistent with applicable country guidelines at the time of study. | |
| Experimental: Three-month ART dispensing<br>Providers at facilities randomized to three-month ART dispensing will be expected to provide all enrolled patients with a 90-day supply of ART and associated HIV medications (cotrimoxazole and isoniazid if part of country guidelines). All other aspects of care will be as per standard of care for the enrolling clinic. | Other: Three-month ART dispensing<br>* Patients enrolled in the three-month ART dispensing arm will receive a 90-day supply of ART from their provider for the duration of the study.<br>|
| Experimental: Six-month ART dispensing<br>Providers at facilities randomized to six-month ART dispensing will be expected to provide all enrolled patients with a 180-day supply of ART and associated HIV medications (cotrimoxazole and isoniazid if part of country guidelines). All other aspects of care will be as per standard of care for the enrolling clinic. | Other: Six-month ART dispensing<br>* Patients enrolled in the six-month ART dispensing arm will receive a 180-day supply of ART from their provider for the duration of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retention in Care at 12 Months | The primary outcome to be studied is whether scripting/dispensing of ART for intervals of six months is non-inferior to three months with respect to retention in care. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic Suppression at 12 Months | The secondary outcome to be studied is whether scripting/dispensing of ART for intervals of six months is non-inferior to three months with respect to a viral load outcome of <1,000 copies/ml (undetectable) at 12 months. | 12 months | 
| Provider Cost Per Patient by Outcome (USD) (Mean, 95% CI) | The secondary outcome to be studied is the cost-effectiveness of scripting/dispensing of ART for intervals of six months compared to three months and SOC. Cost-effectiveness will be estimated as the average cost per successful outcome (patient retained at 12 months). | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antiretroviral therapy, retention, ART, cost-effectiveness, virologic suppression