Genotype-Informed Versus Empiric Management of VirEmia

NCT ID: NCT04233242

Last Updated: 2024-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 286 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-03
• Study Completion Date: 2023-07-08

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.

Conditions

HIV-1-infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Intervention

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.

Group Type: EXPERIMENTAL

Clinical management informed by HIV-1 genotypic resistance testing

Intervention Type: OTHER

The study intervention will consist of the following components:

1. Genotypic resistance testing (GRT);

2. Review of GRT results by an expert committee providing a treatment recommendation;

3. GRT-based decision on further therapy (switch or maintain current ART regimen; choice of regimen); and

4. GRT-informed adherence support.

Control

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Clinical management informed by HIV-1 genotypic resistance testing

The study intervention will consist of the following components:

1. Genotypic resistance testing (GRT);

2. Review of GRT results by an expert committee providing a treatment recommendation;

3. GRT-based decision on further therapy (switch or maintain current ART regimen; choice of regimen); and

4. GRT-informed adherence support.

Intervention Type: OTHER

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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: collaborator

University of Basel

OTHER

Sponsor Role: collaborator

SolidarMed, Partnerships for Health

UNKNOWN

Sponsor Role: collaborator

Seboche Mission Hospital

UNKNOWN

Sponsor Role: collaborator

Ifakara Health Institute

OTHER

Sponsor Role: collaborator

Baylor College of Medicine Children's Foundation

UNKNOWN

Sponsor Role: collaborator

Swiss Tropical & Public Health Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Niklaus D Labhardt, MD, MIH

Role: STUDY_CHAIR

Swiss Tropical & Public Health Institute

Jennifer A Brown, PhD

Role: PRINCIPAL_INVESTIGATOR

Swiss Tropical & Public Health Institute

Thomas Klimkait, PhD

Role: STUDY_DIRECTOR

University of Basel

Josephine Muhairwe, MD, MPH

Role: STUDY_DIRECTOR

SolidarMed, Partnerships for Health

Buntshi P Kayembe, MD

Role: STUDY_DIRECTOR

Baylor College of Medicine Children's Foundation Lesotho

Mosa M Hlasoa, MD

Role: STUDY_DIRECTOR

Baylor College of Medicine Children's Foundation Lesotho

Isaac Ringera, MPH, RN

Role: STUDY_DIRECTOR

SolidarMed, Partnerships for Health

Maja Weisser, MD

Role: STUDY_DIRECTOR

Swiss Tropical & Public Health Institute

Ezekiel Luoga, MD

Role: STUDY_DIRECTOR

Ifakara Health Institute

Tracy R Glass, PhD

Role: STUDY_DIRECTOR

Swiss Tropical & Public Health Institute

Locations

Seboche Mission Hospital

Seboche, Butha-Buthe, Lesotho

Baylor Clinic Leribe

Hlotse, Leribe District, Lesotho

Baylor Clinic Butha-Buthe

Butha-Buthe, , Lesotho

Baylor Clinic Maseru

Maseru, , Lesotho

Baylor Clinic Mohale's Hoek

Mohale's Hoek, , Lesotho

Baylor Clinic Mokhotlong

Mokhotlong, , Lesotho

One-Stop Clinic and Chronic Diseases Clinic (CDCI) at St Francis Referral Hospital

Ifakara, Morogoro, Tanzania

Mbagala Rangi Tatu Hospital

Dar es Salaam, , Tanzania

Temeke Regional Referral Hospital

Dar es Salaam, , Tanzania

Upendano Dispensary

Dar es Salaam, , Tanzania

Countries

Lesotho; Tanzania

References

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.

Reference Type: BACKGROUND

PMID: 33076866 (View on PubMed)

Brown JA, Ringera IK, Luoga E, Bresser M, Mothobi B, Kabundi L, Ilunga M, Mokhele K, Isaac AB, Tsoaeli N, Mbaya T, Simba B, Mayogu K, Mabula E, Cheleboi M, Molatelle M, Kimera N, Mollel GJ, Sando D, Tschumi N, Amstutz A, Thahane L, Hlasoa MM, Kayembe BP, Muhairwe J, Klimkait T, Glass TR, Weisser M, Labhardt ND. Resistance-informed versus empirical management of viraemia in children and adolescents with HIV in Lesotho and Tanzania (GIVE MOVE trial): a multisite, open-label randomised controlled trial. Lancet Glob Health. 2024 Aug;12(8):e1312-e1322. doi: 10.1016/S2214-109X(24)00183-9.

Reference Type: RESULT

PMID: 39030062 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.givemove.org/

trial website

Other Identifiers

REG-19-008

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ID 229-2019

Identifier Type: OTHER

Identifier Source: secondary_id

Req-2019-01275

Identifier Type: OTHER

Identifier Source: secondary_id

12-2020

Identifier Type: OTHER

Identifier Source: secondary_id

NIMR/HQ/R.8a/Vol. IX/3222

Identifier Type: OTHER

Identifier Source: secondary_id

TMDA0020/CTR/0003/03

Identifier Type: OTHER

Identifier Source: secondary_id

P001-20-1.4

Identifier Type: -

Identifier Source: org_study_id