Varying intervals of antiretroviral medication dispensing to improve outcomes for HIV patients (The INTERVAL Study): study protocol for a randomized controlled trial

Risa Hoffman, Ashley Bardon, Sydney Rosen, Matthew Fox, Thoko Kalua, Thembi Xulu, Angela Taylor, Ian Sanne, Risa Hoffman, Ashley Bardon, Sydney Rosen, Matthew Fox, Thoko Kalua, Thembi Xulu, Angela Taylor, Ian Sanne

Abstract

Background: Requirements for frequent dispensing of antiretroviral therapy (ART) place demands on health systems and can lead to suboptimal adherence and disengagement in care for patients due to the time and cost of frequent clinic visits. Rigorous data are needed to define optimal ART dispensing strategies and to evaluate the impact of a longer medication supply on retention and virologic suppression and determine whether this strategy lowers costs for both the patient and the health system. To date, no randomized studies have tested the benefits of 6-month dispensing of ART compared to 3-month and standard of care approaches.

Methods: This study will be an unblinded cluster-randomized, matched controlled trial conducted among 8200 stable, HIV-infected individuals age 18 years and older on ART in Malawi and Zambia, to compare three ART dispensing intervals on the outcomes of retention in care (primary outcome), virologic suppression, and cost-effectiveness. Thirty clusters will be matched according to country, facility type, and ART cohort size and randomized to one of three study arms: standard of care, 3-month dispensing, and 6-month dispensing. Study participants will be followed, and outcomes will be measured at 12, 24, and 36 months. A subset of participants (n = 240) and providers (n = 180) will also participate in qualitative interviews to evaluate feasibility and acceptability of different ART dispensing intervals.

Discussion: This study will be the first to compare 6-month and 3-month ART dispensing intervals for stable, HIV-infected individuals in Malawi and Zambia. We focus on outcomes relevant to country programs, including retention, virologic suppression, and cost-effectiveness. Results from the study will help resource-limited health systems better understand the full scope of outcomes resulting from various ART dispensing intervals and help to inform health policy decisions.

Trial registration: ClinicalTrials.gov, NCT03101592 . Registered on 18 March 2017. Pan African Clinical Trials, PACTR201706002336105 . Registered on 2 June 2017.

Keywords: ART dispensing; Africa; Antiretroviral therapy; Cost-effectiveness; HIV; Retention; Virologic suppression.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol has been reviewed and approved by the institutional review board (IRB) at the University of California, Los Angeles (UCLA), the National Health Sciences Research Council (NHSRC) in Malawi, and the Excellence in Research Ethics and Science (ERES) Converge IRB in Zambia. Any protocol modifications will be submitted to the IRB committees for review, and participants will be informed, if warranted. Informed consent will be obtained from all study participants prior to enrollment.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of study protocol. *See Table 1. ART antiretroviral therapy
Fig. 2
Fig. 2
SPIRIT Figure. *Default defined as out of antiretroviral therapy (ART) for more than 60 days; &Zambia only; ^Malawi only; CPT: co-trimoxazole prophylaxis therapy; IPT: isoniazid preventive therapy

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