Clinical trial NCT03101592: INTERVAL: Varying Intervals of ART to Improve Outcomes in HIV
Official title: INTERVAL: Varying Intervals of ART to Improve Outcomes in HIV
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: HIV-1-infection
Keywords: antiretroviral therapy
retention
ART
cost-effectiveness
virologic suppression
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: Boston University
name: Equip, Lesotho
name: Ministry of Health, Malawi
name: Ministry of Health, Zambia
name: Partners in Hope, Inc.
name: Right to Care
name: United States Agency for International Development (USAID)
First posted: 2017-04-05
Enrollment: 9118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Retention in Care at 12 Months
timeFrame: 12 months
Secondary outcomes:
measure: Virologic Suppression at 12 Months
timeFrame: 12 months
measure: Provider Cost Per Patient by Outcome (USD) (Mean, 95% CI)
timeFrame: 12 months
Other outcomes:
Locations:
city: Lilongwe
country: Malawi
facility: Partners in Hope
city: Lusaka
country: Zambia
facility: EQUIP Zambia
Study officials:
affiliation: University of California, Los Angeles
name: Risa M Hoffman, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.