CClinicalTrials.gg
Status unknownNCT03438370[MMD]Updated Feb 19, 2018

Outcomes of Differentiated Models of Antiretroviral Treatment (ART) Provision

An interventional study of Three monthly ART supply at CAGs and Six monthly ART supply at outreaches in HIV/AIDS, sponsored by Equip, Lesotho. Status unknown at 1 site in Lesotho. Open to participants aged 18 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-02-19.

Sponsored by Equip, Lesotho · Not applicable, Interventional, and Health services research

The sponsor has not verified this record recently (last verified Aug 2017), so the status shown — last known as Recruiting — may be out of date.
Phase
Not applicable
Study type
Interventional
Enrollment
5,760
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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.
Read the 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.

02

Conditions studied

03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
04

Study design

Phase
Not applicable
Primary purpose
Health services research
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
5,760 participants (estimated)

Study arms

  • No intervention
    Three monthly ART supply at facilities

    Sites at which patients will be provided three monthly ART supply at health facilities.

  • Experimental
    Three monthly ART supply at CAGs

    Sites at which patients will be provided three monthly ART supply at Community ART Groups (CAGs).

    Other: Three monthly ART supply at CAGs

  • Experimental
    Six monthly ART supply at outreaches

    Sites at which patients will be provided six monthly ART supply at Community distribution points or outreaches.

    Other: Six monthly ART supply at outreaches

Interventions

  • OtherThree monthly ART supply at CAGs

    Sites where three monthly ART supply will be provided at outreaches

  • OtherSix monthly ART supply at outreaches

    Sites where six monthly ART will supply will be provided at outreaches

05

What researchers measure

Primary outcomes

  1. retention in care

    The proportion of patients remaining in care 12 months after study enrolment

    Time frame: 12 months

Secondary outcomes

  1. Viral suppression

    The proportion of patients with virological suppression (\<1000 copies/ml) 12 months after study enrolment

    Time frame: 12 months

  2. Cost of providing ART

    The cost per patient of providing ART in each of the three arms (from a provider perspective)

    Time frame: 12 months

  3. Cost of retaining a patient

    The provider cost per patient retained and provider cost per patient retained with virological suppression in each of the three arms

    Time frame: 12 months

06

Study locations

1 of 1 sites recruiting
07

References and documents

Publications

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  • Government of Lesotho. National guidelines on the use of antiretroviral therapy for HIV prevention and treatment. In: MOH, editor.2014
  • MOH Lesotho. GLOBAL AIDS RESPONSE PROGRESS REPORT 2015. 2015 Reporting Period: January - December 2014.
  • Guideline on When to Start Antiretroviral Therapy and on Pre-Exposure Prophylaxis for HIV. Geneva: World Health Organization; 2015 Sep. Available from http://www.ncbi.nlm.nih.gov/books/NBK327115/ PubMed 26598776 ↗
  • Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. 2nd edition. Geneva: World Health Organization; 2016. Available from http://www.ncbi.nlm.nih.gov/books/NBK374294/ PubMed 27466667 ↗
  • Teck R. Reducing frequency of ARV pick-ups for HIV patients stabilised on ARV treatment 2015.
  • Lesotho Go. Lesotho CAG toolkit In: MOH, editor.2015.
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  • World Health Organization. Retention in HIV programmes: defining the challenges and identifying solutions: meeting report, 13-15 September 2011. 2012.
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  • Fatti G, Ngorima-Mabhena N, Tiam A, Tukei BB, Kasu T, Muzenda T, Maile K, Lombard C, Chasela C, Grimwood A. Community-based differentiated service delivery models incorporating multi-month dispensing of antiretroviral treatment for newly stable people living with HIV receiving single annual clinical visits: a pooled analysis of two cluster-randomized trials in southern Africa. J Int AIDS Soc. 2021 Oct;24 Suppl 6(Suppl 6):e25819. doi: 10.1002/jia2.25819. PubMed 34713614 ↗
  • Lopes J, Grimwood A, Ngorima-Mabhena N, Tiam A, Tukei BB, Kasu T, Mahachi N, Mothibi E, Tukei V, Chasela C, Lombard C, Fatti G. Out-of-Facility Multimonth Dispensing of Antiretroviral Treatment: A Pooled Analysis Using Individual Patient Data From Cluster-Randomized Trials in Southern Africa. J Acquir Immune Defic Syndr. 2021 Dec 15;88(5):477-486. doi: 10.1097/QAI.0000000000002797. PubMed 34506343 ↗
  • Tukei BB, Fatti G, Tiam A, Ngorima-Mabhena N, Tukei VJ, Tshabalala I, Sejana VM, Muzenda T, Mokoroane LM, Sehlabo L, Maotoe T, Mirembe JK, Membe I, Akpan F, Maile K, Faturiyele I, Xulu T, Minior T, Sanne I, Chasela C; for EQUIP Health. Twelve-Month Outcomes of Community-Based Differentiated Models of Multimonth Dispensing of ART Among Stable HIV-Infected Adults in Lesotho: A Cluster-Randomized Noninferiority Trial. J Acquir Immune Defic Syndr. 2020 Nov 1;85(3):280-291. doi: 10.1097/QAI.0000000000002439. PubMed 32665460 ↗
  • Faturiyele IO, Appolinare T, Ngorima-Mabhena N, Fatti G, Tshabalala I, Tukei VJ, Pisa PT. Outcomes of community-based differentiated models of multi-month dispensing of antiretroviral medication among stable HIV-infected patients in Lesotho: a cluster randomised non-inferiority trial protocol. BMC Public Health. 2018 Aug 29;18(1):1069. doi: 10.1186/s12889-018-5961-0. PubMed 30157896 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03438370
Lead sponsor
Equip, Lesotho
Collaborators
Ministry of Health, Lesotho, United States Agency for International Development (USAID), Elizabeth Glaser Pediatric AIDS Foundation, Lesotho Network of AIDS Services Organizations, National Drugs Service Organisation of Lesotho, Chemonics
Responsible party
Sponsor
First posted
Feb 19, 2018
Start date
Aug 7, 2017
Primary completion
Aug 2019 (estimated)
Completion
Sep 2019 (estimated)
Last update
Feb 19, 2018

Study contacts

Iyiola Faturiyele, MBChB, MPH
Contact
Iyiola.Faturiyele@equiphealth.org
00266 5939 9691
Khotso Maile, MSc
Contact
Kgotso.Maile@equiphealth.org
00266 5709 9967
Iyiola Faturiyele, MBChB, MPH
principal investigator · Member, Southern Africa HIV Clinician Society, Johannesburg, South Africa, 2010-present

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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