INTERVAL: Varying Intervals of ART to Improve Outcomes in HIV (INTERVAL)

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.

Study Overview

• Status: Terminated
• Conditions: HIV-1-infection
• Intervention / Treatment: Other: Three-month ART dispensing; Other: Six-month ART dispensing

Detailed Description

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:

1. Retention in care on strategy
2. 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.

• Study Type: Interventional
• Enrollment (Actual): 9118
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Malawi
  • Lilongwe, Malawi
    • Partners in Hope
• Zambia
  • Lusaka, Zambia
    • EQUIP Zambia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of care ART dispensing; 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; 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; 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.
Experimental: Six-month ART dispensing; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Boston University; United States Agency for International Development (USAID); Ministry of Health, Zambia; Ministry of Health, Malawi; Right to Care; Partners in Hope; Equip, Lesotho
• Investigators: Principal Investigator: Risa M Hoffman, MD, MPH, University of California, Los Angeles

Publications and helpful links

General Publications

• Hoffman RM, Moyo C, Balakasi KT, Siwale Z, Hubbard J, Bardon A, Fox MP, Kakwesa G, Kalua T, Nyasa-Haambokoma M, Dovel K, Campbell PM, Tseng CH, Pisa PT, Cele R, Gupta S, Benade M, Long L, Xulu T, Sanne I, Rosen S. Multimonth dispensing of up to 6 months of antiretroviral therapy in Malawi and Zambia (INTERVAL): a cluster-randomised, non-blinded, non-inferiority trial. Lancet Glob Health. 2021 May;9(5):e628-e638. doi: 10.1016/S2214-109X(21)00039-5.
• Phiri K, McBride K, Siwale Z, Hubbard J, Bardon A, Moucheraud C, Haambokoma M, Pisa PT, Moyo C, Hoffman RM. Provider experiences with three- and six-month antiretroviral therapy dispensing for stable clients in Zambia. AIDS Care. 2021 Apr;33(4):541-547. doi: 10.1080/09540121.2020.1755010. Epub 2020 May 4.
• Hoffman R, Bardon A, Rosen S, Fox M, Kalua T, Xulu T, Taylor A, Sanne I. Varying intervals of antiretroviral medication dispensing to improve outcomes for HIV patients (The INTERVAL Study): study protocol for a randomized controlled trial. Trials. 2017 Oct 13;18(1):476. doi: 10.1186/s13063-017-2177-z.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2017
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): August 10, 2020

Study Registration Dates

• First Submitted: March 18, 2017
• First Submitted That Met QC Criteria: March 29, 2017
• First Posted (Actual): April 5, 2017

Study Record Updates

• Last Update Posted (Actual): October 27, 2020
• Last Update Submitted That Met QC Criteria: October 4, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: cost-effectiveness; retention; ART; antiretroviral therapy; virologic suppression
• Other Study ID Numbers: 16-001652

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No