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Genotype-Informed Versus Empiric Management of VirEmia (GIVE MOVE)

Primary Purpose

HIV-1-infection

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Clinical management informed by HIV-1 genotypic resistance testing
Sponsored by
Swiss Tropical & Public Health Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for HIV-1-infection focused on measuring HIV-1, acquired immunodeficiency syndrome, drug resistance, treatment failure, child, adolescent, Lesotho, Tanzania

Eligibility Criteria

6 Months - 19 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • In care in a study site
  • Age ≥6 months and <19 years
  • Latest HIV viral load result ≥400 c/mL
  • On an unchanged ART regimen for ≥6 months
  • Phlebotomy for latest viral load test <4 months before screening
  • Consent given

Exclusion Criteria:

  • Indication for treatment switch according to WHO guidelines at screening
  • 1st enhanced adherence counselling (EAC) session initiated >2 weeks prior to screening
  • Intention to transfer out of the study site (and not into a different study site) within 3 months after randomisation
  • Already enrolled in another study if judged as non-compatible by the (Local) Principal Investigator
  • Pregnant or breastfeeding at screening (no exclusion based on pregnancy or breastfeeding after enrolment)
  • Acute illness requiring hospitalisation at screening (no exclusion based on hospitalisation after enrolment)
  • Received a resistance test in the last 12 months

Sites / Locations

  • Seboche Mission Hospital
  • Baylor Clinic Leribe
  • Baylor Clinic Butha-Buthe
  • Baylor Clinic Maseru
  • Baylor Clinic Mohale's Hoek
  • Baylor Clinic Mokhotlong
  • One-Stop Clinic and Chronic Diseases Clinic (CDCI) at St Francis Referral Hospital
  • Mbagala Rangi Tatu Hospital
  • Temeke Regional Referral Hospital
  • Upendano Dispensary

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Intervention

Control

Arm Description

The viral load ≥400 c/mL before enrolment triggers genotypic resistance testing (GRT), followed by GRT-informed patient management and counselling. Onward treatment is informed by the resistance profile determined through GRT, with a GRT Expert Committee issuing a treatment recommendation.

Standard of care according to national guidelines and recommendations of the World Health Organization: The viral load ≥400 c/mL before enrolment is followed by 3 sessions of enhanced adherence counselling and a follow-up viral load test. Onward treatment is informed by viral load testing.

Outcomes

Primary Outcome Measures

Composite primary endpoint
The composite primary endpoint is the occurrence of any one or more of the events i) death due to any cause during the follow-up period (36 weeks), ii) HIV- or ART-related hospital admission of ≥24 hours duration (possibly, probably or definitely related to HIV or ART, judged by the endpoint committee blinded to the study arm) during the follow-up period (36 weeks), iii) new clinical World Health Organization (WHO) stage IV event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis; judged by the endpoint committee blinded to the study arm) during the follow-up period (36 weeks), and iv) no documentation of a suppressed viral load (<50 c/mL) at 9 months follow-up (window: 32-44 weeks). The primary endpoint will be assessed as an event ratio of participants reaching one or more of the composite endpoints.

Secondary Outcome Measures

Proportion with death due to any cause
Proportion of participants confirmed dead during the follow-period among all participants enrolled.
Proportion with HIV- or ART-related hospital admission of ≥24 hours duration
Proportion of participants with HIV- or ART-related hospital admission of ≥24 hours duration (possibly, probably or definitely related to HIV or ART, judged by the endpoint committee) during the follow-up period among all participants enrolled.
Proportion with new clinical WHO stage IV event(s) (with some exclusions)
Proportion of participants with new clinical WHO stage IV event(s) (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis; judged by the endpoint committee) during the follow-up period among all participants enrolled.
Proportion without documentation of a suppressed viral load
Proportion of participants without documentation of viral load <50 c/mL at 9 months among all participants enrolled.
Proportion lost to follow-up
Proportion of participants with no documented clinic visit at 9 months among all participants enrolled.
Proportion with observed virologic failure
Proportion of participants with a viral load ≥50 c/mL among all participants with a viral load result at 9 months.
Composite endpoint
This composite endpoint is the proportion of participants among all participants enrolled experiencing one or more of the events i) death due to any cause within 24 weeks of the decision on onward treatment, ii) HIV- or ART-related hospital admission of ≥24 hours duration (possibly, probably or definitely related to HIV or ART) within 24 weeks of the decision on onward treatment, iii) new clinical WHO stage IV event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis) within 24 weeks of the decision on onward treatment, and iv) no documentation of a suppressed viral load (<50 c/mL) at 6 months (window: 20-28 weeks) after the decision on onward treatment. The decision on onward treatment is defined as the first visit after the follow-up viral load result or resistance test result becomes available in the control or intervention arm, respectively.

Full Information

First Posted
January 11, 2020
Last Updated
August 18, 2023
Sponsor
Swiss Tropical & Public Health Institute
Collaborators
University Hospital, Basel, Switzerland, University of Basel, SolidarMed, Partnerships for Health, Seboche Mission Hospital, Ifakara Health Institute, Baylor College of Medicine Children's Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT04233242
Brief Title
Genotype-Informed Versus Empiric Management of VirEmia
Acronym
GIVE MOVE
Official Title
Genotype-Informed Versus Empiric Management of VirEmia (GIVE MOVE) in HIV-Infected Children and Adolescents on Antiretroviral Therapy: An Open-Label Randomised Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
March 3, 2020 (Actual)
Primary Completion Date
March 15, 2023 (Actual)
Study Completion Date
July 8, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swiss Tropical & Public Health Institute
Collaborators
University Hospital, Basel, Switzerland, University of Basel, SolidarMed, Partnerships for Health, Seboche Mission Hospital, Ifakara Health Institute, Baylor College of Medicine Children's Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
HIV infection can be effectively controlled with antiretroviral therapy (ART). However, children and adolescents living with HIV and receiving ART suffer high rates of treatment failure, predominantly caused by suboptimal adherence to therapy and/or viral drug resistance. While high-income countries routinely use genotypic resistance testing (GRT) to determine which drug combinations are likely to be effective, this diagnostic tool is relatively costly and labour-intensive and is not routinely available in most resource-limited settings. GIVE MOVE is a multi-country (Lesotho, Tanzania) randomised clinical trial assessing if rapid GRT after detecting an unsuppressed viral load improves the clinical management and thus health outcomes for children and adolescents living with HIV. Children and adolescents with an unsuppressed viral load despite ART are enrolled and randomly allocated to a control or an intervention arm (50% of participants in each arm). The control arm receives care according to the current standard of care, consisting of three sessions of enhanced adherence counselling at monthly intervals, followed by a second viral load test. Onward treatment is informed by the outcome of this viral load test alongside empirical guidelines and clinical judgement. The intervention arm receives GRT and GRT-informed onward therapy. Participants in the intervention arm also receive three sessions of enhanced adherence counselling, which is informed by GRT results (i.e., if no drug resistance is detected, there is a high chance of suboptimal adherence to ART and this can be directly addressed). This trial will assess if the rapid provision of GRT improves participants' health outcomes at 9 months after enrolment. A nested study will assess the cost and cost-effectiveness of GRT. Thus, this trial will provide evidence on whether the provision of GRT for children and adolescents with HIV should be prioritised in resource-limited settings.
Detailed Description
Background and rationale: Children and adolescents living with HIV and receiving antiretroviral therapy (ART) suffer high rates of treatment failure, predominantly caused by suboptimal adherence to therapy and/or viral drug resistance. While high-income countries routinely use genotypic resistance testing (GRT) to select an optimal ART regimen, this diagnostic tool is not routinely available in many resource-limited settings. Objective: The GIVE MOVE trial assesses if rapid GRT after detection of an unsuppressed viral load in children and adolescents on ART improves health outcomes when compared to the current standard of care. Furthermore, a nested study will assess the cost-effectiveness of this intervention. Combined, these results will provide evidence on whether GRT should be prioritised for children and adolescents with HIV. Study design: GIVE MOVE is a multi-centre (several centres in 2 countries, Lesotho and Tanzania), parallel-group (1:1 allocation), open-label randomised clinical trial. Children and adolescents living with HIV with a viral load ≥400 c/mL are enrolled. The control group is managed as per the current standard of care that follows the World Health Organization guidelines, i.e. three sessions of enhanced adherence counselling at monthly intervals, followed by a second viral load test and viral load-informed onward treatment. In the intervention arm, participants receive GRT, a GRT-informed treatment recommendation by a GRT Expert Committee, and GRT-informed onward therapy, selecting the best locally available drugs according to the drug resistance profile. The GIVE MOVE trial will compare clinical outcomes (mortality, morbidity, viral suppression; see the Primary Outcome section for the composite primary endpoint) at nine months. Assuming that 20% vs 35% reach the primary endpoint in the intervention vs control arm, and at a significance level of 5%, 276 participants (138 per arm) are required to reach 80% power. In addition to clinical outcomes, the trial intends to assess the cost and cost-effectiveness of the intervention. The GIVE MOVE trial aims at informing future clinical guidelines on the management of paediatric HIV.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1-infection
Keywords
HIV-1, acquired immunodeficiency syndrome, drug resistance, treatment failure, child, adolescent, Lesotho, Tanzania

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Multi-centre, open-label, parallel-group (1:1 allocation), superiority randomised clinical trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
286 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Experimental
Arm Description
The viral load ≥400 c/mL before enrolment triggers genotypic resistance testing (GRT), followed by GRT-informed patient management and counselling. Onward treatment is informed by the resistance profile determined through GRT, with a GRT Expert Committee issuing a treatment recommendation.
Arm Title
Control
Arm Type
No Intervention
Arm Description
Standard of care according to national guidelines and recommendations of the World Health Organization: The viral load ≥400 c/mL before enrolment is followed by 3 sessions of enhanced adherence counselling and a follow-up viral load test. Onward treatment is informed by viral load testing.
Intervention Type
Other
Intervention Name(s)
Clinical management informed by HIV-1 genotypic resistance testing
Intervention Description
The study intervention will consist of the following components: Genotypic resistance testing (GRT); Review of GRT results by an expert committee providing a treatment recommendation; GRT-based decision on further therapy (switch or maintain current ART regimen; choice of regimen); and GRT-informed adherence support.
Primary Outcome Measure Information:
Title
Composite primary endpoint
Description
The composite primary endpoint is the occurrence of any one or more of the events i) death due to any cause during the follow-up period (36 weeks), ii) HIV- or ART-related hospital admission of ≥24 hours duration (possibly, probably or definitely related to HIV or ART, judged by the endpoint committee blinded to the study arm) during the follow-up period (36 weeks), iii) new clinical World Health Organization (WHO) stage IV event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis; judged by the endpoint committee blinded to the study arm) during the follow-up period (36 weeks), and iv) no documentation of a suppressed viral load (<50 c/mL) at 9 months follow-up (window: 32-44 weeks). The primary endpoint will be assessed as an event ratio of participants reaching one or more of the composite endpoints.
Time Frame
At 9 months follow-up visit (window: 32-44 weeks)
Secondary Outcome Measure Information:
Title
Proportion with death due to any cause
Description
Proportion of participants confirmed dead during the follow-period among all participants enrolled.
Time Frame
Within 36 weeks after baseline
Title
Proportion with HIV- or ART-related hospital admission of ≥24 hours duration
Description
Proportion of participants with HIV- or ART-related hospital admission of ≥24 hours duration (possibly, probably or definitely related to HIV or ART, judged by the endpoint committee) during the follow-up period among all participants enrolled.
Time Frame
Within 36 weeks after baseline
Title
Proportion with new clinical WHO stage IV event(s) (with some exclusions)
Description
Proportion of participants with new clinical WHO stage IV event(s) (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis; judged by the endpoint committee) during the follow-up period among all participants enrolled.
Time Frame
Within 36 weeks after baseline
Title
Proportion without documentation of a suppressed viral load
Description
Proportion of participants without documentation of viral load <50 c/mL at 9 months among all participants enrolled.
Time Frame
At 9 months follow-up visit (window: 32-44 weeks)
Title
Proportion lost to follow-up
Description
Proportion of participants with no documented clinic visit at 9 months among all participants enrolled.
Time Frame
At 9 months follow-up visit (window: 32-44 weeks)
Title
Proportion with observed virologic failure
Description
Proportion of participants with a viral load ≥50 c/mL among all participants with a viral load result at 9 months.
Time Frame
At 9 months follow-up visit (window: 32-44 weeks)
Title
Composite endpoint
Description
This composite endpoint is the proportion of participants among all participants enrolled experiencing one or more of the events i) death due to any cause within 24 weeks of the decision on onward treatment, ii) HIV- or ART-related hospital admission of ≥24 hours duration (possibly, probably or definitely related to HIV or ART) within 24 weeks of the decision on onward treatment, iii) new clinical WHO stage IV event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis) within 24 weeks of the decision on onward treatment, and iv) no documentation of a suppressed viral load (<50 c/mL) at 6 months (window: 20-28 weeks) after the decision on onward treatment. The decision on onward treatment is defined as the first visit after the follow-up viral load result or resistance test result becomes available in the control or intervention arm, respectively.
Time Frame
6 months (window: 20-28 weeks) after the decision on onward treatment
Other Pre-specified Outcome Measures:
Title
Time to viral suppression
Description
Time to achieving a viral load <50 c/mL; considering viral load testing done with samples from the 3-, 6- and 9-month study visit in both arms.
Time Frame
3- (window: 10-14 weeks), 6- (window: 20-28 weeks), and 9-month (window: 32-44 weeks) study visit
Title
Proportion with drug regimen switches in the absence of major drug resistance mutations and/or non-switches in the presence of major drug resistance mutations
Description
Proportion of participants with drug regimen switches in the absence of major drug resistance mutations and/or non-switches in the presence of major drug resistance mutations among all participants enrolled (as identified by Sanger sequencing, according to the Stanford HIV drug resistance database).
Time Frame
Baseline and 9-month (window: 32-44 weeks) study visit
Title
Proportion with new drug resistance mutations emerged within the study period
Description
Proportion of participants with new drug resistance mutations emerged within the study period among all participants enrolled.
Time Frame
Change from baseline to 9-month (window: 32-44 weeks) study visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: In care in a study site Age ≥6 months and <19 years Latest HIV viral load result ≥400 c/mL On an unchanged ART regimen for ≥6 months Phlebotomy for latest viral load test <4 months before screening Consent given Exclusion Criteria: Indication for treatment switch according to WHO guidelines at screening 1st enhanced adherence counselling (EAC) session initiated >2 weeks prior to screening Intention to transfer out of the study site (and not into a different study site) within 3 months after randomisation Already enrolled in another study if judged as non-compatible by the (Local) Principal Investigator Pregnant or breastfeeding at screening (no exclusion based on pregnancy or breastfeeding after enrolment) Acute illness requiring hospitalisation at screening (no exclusion based on hospitalisation after enrolment) Received a resistance test in the last 12 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Niklaus D Labhardt, MD, MIH
Organizational Affiliation
Swiss Tropical & Public Health Institute
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jennifer A Brown, PhD
Organizational Affiliation
Swiss Tropical & Public Health Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Thomas Klimkait, PhD
Organizational Affiliation
University of Basel
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Josephine Muhairwe, MD, MPH
Organizational Affiliation
SolidarMed, Partnerships for Health
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Buntshi P Kayembe, MD
Organizational Affiliation
Baylor College of Medicine Children's Foundation Lesotho
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Mosa M Hlasoa, MD
Organizational Affiliation
Baylor College of Medicine Children's Foundation Lesotho
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Isaac Ringera, MPH, RN
Organizational Affiliation
SolidarMed, Partnerships for Health
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Maja Weisser, MD
Organizational Affiliation
Swiss Tropical & Public Health Institute
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Ezekiel Luoga, MD
Organizational Affiliation
Ifakara Health Institute
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Tracy R Glass, PhD
Organizational Affiliation
Swiss Tropical & Public Health Institute
Official's Role
Study Director
Facility Information:
Facility Name
Seboche Mission Hospital
City
Seboche
State/Province
Butha-Buthe
Country
Lesotho
Facility Name
Baylor Clinic Leribe
City
Hlotse
State/Province
Leribe
Country
Lesotho
Facility Name
Baylor Clinic Butha-Buthe
City
Butha-Buthe
Country
Lesotho
Facility Name
Baylor Clinic Maseru
City
Maseru
Country
Lesotho
Facility Name
Baylor Clinic Mohale's Hoek
City
Mohale's Hoek
Country
Lesotho
Facility Name
Baylor Clinic Mokhotlong
City
Mokhotlong
Country
Lesotho
Facility Name
One-Stop Clinic and Chronic Diseases Clinic (CDCI) at St Francis Referral Hospital
City
Ifakara
State/Province
Morogoro
Country
Tanzania
Facility Name
Mbagala Rangi Tatu Hospital
City
Dar Es Salaam
Country
Tanzania
Facility Name
Temeke Regional Referral Hospital
City
Dar es Salaam
Country
Tanzania
Facility Name
Upendano Dispensary
City
Dar Es Salaam
Country
Tanzania

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Upon publication of the trial results, a subset of the key pseudo-anonymised individual participant data collected during the study, along with a data dictionary, will be made available through the data repository Zenodo. The full dataset will be made available upon request to the Division of Clinical Epidemiology at the University Hospital Basel and after signing a data confidentiality agreement.
Citations:
PubMed Identifier
33076866
Citation
Brown JA, Ringera I, Luoga E, Cheleboi M, Kimera N, Muhairwe J, Kayembe BP, Molapo Hlasoa M, Kabundi L, Yav CWD, Mothobi B, Thahane L, Amstutz A, Bachmann N, Mollel GJ, Bresser M, Glass TR, Paris DH, Klimkait T, Weisser M, Labhardt ND. Genotype-Informed Versus Empiric Management Of VirEmia (GIVE MOVE): study protocol of an open-label randomised clinical trial in children and adolescents living with HIV in Lesotho and Tanzania. BMC Infect Dis. 2020 Oct 19;20(1):773. doi: 10.1186/s12879-020-05491-9.
Results Reference
background
Links:
URL
https://www.givemove.org/
Description
trial website

Learn more about this trial

Genotype-Informed Versus Empiric Management of VirEmia

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