Clinical trial NCT03438370: Outcomes of Differentiated Models of Antiretroviral Treatment (ART) Provision
Official title: Outcomes of Differentiated Models of Antiretroviral Treatment (ART) Provision: Multi-Month Dispensing (MMD) of ART in Community ART Distribution for Stable HIV Infected Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: HIV/AIDS
Lead sponsor: Equip, Lesotho
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Lesotho
name: United States Agency for International Development (USAID)
name: Elizabeth Glaser Pediatric AIDS Foundation
name: Lesotho Network of AIDS Services Organizations
name: National Drugs Service Organisation of Lesotho
name: Chemonics
First posted: 2018-02-19
Enrollment: 5760
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cluster Randomized Trial comparing three different antiretroviral therapy (ART) dispensing strategies.
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The aim of this study is to evalulate the effectiveness and cost-effectiveness of three models of ART provision for stable ART patients. The objectives are to measure patient retention, virological suppression, provider and patient costs, cost-effectiveness, and patient acceptability amongst stable patients who receive ART at intervals of three and six months within community distribution models, and to compare these to patients who receive ART directly from the clinic at three month intervals.

Methods

A prospective, parallel, cluster-randomized non-inferiority trial with three study arms will be conducted. 30 Clusters (sites) will be randomized in strata according to geographic location (urban and rural) to the 3 study arms as follows:

* Control arm: sites at which patients will receive three monthly ART supply at the facility (arm 3MF).
* Intervention arm 1: sites at which patients will receive three monthly ART supply in CAGs (arm 3MC)
* Intervention arm 2: sites at which patients will receive six monthly ART supply in the community by a healthcare worker (arm 6MCD).

The study population will consist of stable, HIV-infected adults who have received first-line ART for at least six months, who have a viral load \<1000 copies/ml at baseline, and who provide informed consent for inclusion in the study. An average of 192 participants from each study site will be included, with a total sample size of approximately 5760 participants.

The primary outcome is retention in care defined as the proportion of patients remaining in care 12 months after study enrolment, with the hypothesis that patient retention within the intervention arms will be non-inferior compared to the control arm. Retention in care will also be compared between the three arms after 24 months.

The secondary outcomes are:

* Viral suppression: defined as the proportion of patients with virological suppression (\<1000 copies/ml) 12 and 24 months after study enrolment;
* Cost of providing ART: defined as the cost per patient of providing ART in each of the three arms (from a provider perspective);
* Cost of retaining a patient: defined as the provider cost per patient retained and provider cost per patient retained with virological suppression in each of the three arms, and the incremental cost-effectiveness ratio for the comparative arms.

Detailed description: Background In 2015, sub-Saharan Africa was still the region most affected by the HIV epidemic, with 25.6 (23.1-28.5) million people living with HIV in 2015. It is estimated that 42% of all people living with HIV (PLHIV) in Lesotho were receiving ART by 2015.The United States Government's President's Emergency Plan for AIDS Relief (PEPFAR) has adopted the goals of 90-90-90 from UNAIDS, and is supporting a swift implementation of the new World Health Organization'sTest and Start guidelines.With these goals, PEPFAR also sets out to reduce new infections by 75% and to attain zero discrimination and stigma for all PLHIV.

To assist countries to reach the goal of universal coverage, EQUIP Innovation for health (a new field support award from the USAID Office of HIV and AIDS that supports innovations in HIV clinical and community-based HIV treatment related services) is evaluating communitybased care, treatment and support models to create an enabling environment for massive scale-up of ART delivery and adherence support. Based on this background, EQUIP and and Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) propose to conduct operational research that seeks to understand and measure the effectiveness of implementing a package of services that include multi-month dispensing (MMD) of ART drugs, Community ART distribution models through Community ART Groups (CAGs) and Community Distribution points and routine viral load monitoring of stable patients in communities of PEPFAR/USAID Lesotho scale-up districts.

The aim of this study is to evalulate the effectiveness and cost-effectiveness of three models of ART provision for stable ART patients. The objectives are to measure patient retention, virological suppression, provider and patient costs, cost-effectiveness, and patient acceptability amongst stable patients who receive ART at intervals of three and six months within community distribution models, and to compare these to patients who receive ART directly from the clinic at three month intervals.

Methods

A prospective, parallel, cluster-randomized non-inferiority trial with three study arms will be conducted. 30 Clusters (sites) will be randomized in strata according to geographic location (urban and rural) to the 3 study arms as follows:

* Control arm: sites at which patients will receive three monthly ART supply at the facility (arm 3MF).
* Intervention arm 1: sites at which patients will receive three monthly ART supply in CAGs (arm 3MC)
* Intervention arm 2: sites at which patients will receive six monthly ART supply in the community by a healthcare worker (arm 6MCD).

Sites for inclusion in the study will be selected at which it is deemed to be feasible to implement multi-month dispensing of ART in the community.

The study population will consist of stable, HIV-infected adults who have received first-line ART for at least six months, who have a viral load \<1000 copies/ml at baseline, and who provide informed consent for inclusion in the study. An average of 192 participants from each study site will be included, with a total sample size of approximately 5760 participants. For those sites randomized to the 3MC arm, enrolled participants will be part of a CAG for the duration of the study. For those sites randomized to the 6MCD arm, enrolled participants will be dispensed a 6-month supply of ART in the community by a healthcare worker in between their annual clinical assessments. All participants will have a clinical assessment and viral load testing at the clinic at least annually, and participants will be followed-up for 24 months after enrolment.

The primary outcome is retention in care defined as the proportion of patients remaining in care 12 months after study enrolment, with the hypothesis that patient retention within the intervention arms will be non-inferior compared to the control arm. Retention in care will also be compared between the three arms after 24 months.

The secondary outcomes are:

* Viral suppression: defined as the proportion of patients with virological suppression (\<1000 copies/ml) 12 and 24 months after study enrolment;
* Cost of providing ART: defined as the cost per patient of providing ART in each of the three arms (from a provider perspective);
* Cost of retaining a patient: defined as the provider cost per patient retained and provider cost per patient retained with virological suppression in each of the three arms, and the incremental cost-effectiveness ratio for the comparative arms.

Qualitative research will include assessing the acceptability of multi-month dispensing of ART within CAGs and the community from both a patient and healthcare provider perspective. Costs to patients will be compared between the three arms from data derived from patient surveys. In addition, indicators of potential facility level decongestion will be compared between arms, which will include the median facility patient waiting time and average monthly number of patients newly initiated on ART, with data derived from site surveys and routine facility-level data.

This study will follow the ethical considerations specified by the Lesotho National Health Research and Ethics Committee.

The results of the study are expected to inform health policy both nationally and regionally regarding the effectiveness of implementing a package of services consisting of MMD within CAGs and community distribution together with viral load monitoring for stable ART patients.

Eligibility criteria: Inclusion Criteria:

* At least 18 years of age and willing and able to provide written informed consent for participation in this study.
* Willing to participate in the multi-month dispensing model that the patient's study site has been randomized to.
* On ART ≥ 6 months with no periods of defaulting from ART since the last viral load result (ART default defined as missing 7 or more consecutive days of ART)
* On first-line ART regimen (substitutions within the first-line regimen prior to the last viral load test are permissible).
* No ARV drug substitutions since the last viral load result \< 1,000 copies per ml
* Plasma or dried-blood spot viral load \< 1,000 copies/ml in a patient who has been on first-line ART for at least 6 months, with viral load drawn within last 12 months of enrollment while patient is receiving ART

Exclusion Criteria:

* On second-line ART regimen.
* Patients with co-morbidities requiring facility visits more often than 6 monthly.
* ART substitutions since last VL test.
* Diagnosed with a WHO clinical stage 3 or 4 condition within the past 3 months.
* Pregnant or less than 12 months postpartum and breastfeeding mothers.
* Participating in another study that involves dispensing interval, adherence, or retention or involves receiving medications.

Primary outcomes:
measure: retention in care
timeFrame: 12 months
Secondary outcomes:
measure: Viral suppression
timeFrame: 12 months
measure: Cost of providing ART
timeFrame: 12 months
measure: Cost of retaining a patient
timeFrame: 12 months
Other outcomes:
Locations:
city: Maseru
country: Lesotho
facility: Ha Tlali
Study officials:
affiliation: Member, Southern Africa HIV Clinician Society, Johannesburg, South Africa, 2010-present
name: Iyiola Faturiyele, MBChB, MPH
role: PRINCIPAL_INVESTIGATOR
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