Genotype-Informed Versus Empiric Management of VirEmia

NCT04233242 | Completed DMC

• 7 other identifiers: P001-20-1.4REG-19-008ID 229-2019Req-2019-0127512-2020NIMR/HQ/R.8a/Vol. IX/3222TMDA0020/CTR/0003/03
• Study Type: interventional
• Target: 286
• Locations: 2 countries
• Sites: 10

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.

Conditions

HIV-1-infection

Keywords

HIV-1; acquired immunodeficiency syndrome; drug resistance; treatment failure; child; adolescent; Lesotho; Tanzania

Outcome Measures

Primary Outcomes (1)

• 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.

  At 9 months follow-up visit (window: 32-44 weeks)

Secondary Outcomes (7)

• Proportion with death due to any cause

  Within 36 weeks after baseline

• Proportion with HIV- or ART-related hospital admission of ≥24 hours duration

  Within 36 weeks after baseline

• Proportion with new clinical WHO stage IV event(s) (with some exclusions)

  Within 36 weeks after baseline

• Proportion without documentation of a suppressed viral load

  At 9 months follow-up visit (window: 32-44 weeks)

• Proportion lost to follow-up

  At 9 months follow-up visit (window: 32-44 weeks)

Other Outcomes (3)

• Time to viral suppression

  3- (window: 10-14 weeks), 6- (window: 20-28 weeks), and 9-month (window: 32-44 weeks) study visit

• 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

  Baseline and 9-month (window: 32-44 weeks) study visit

• Proportion with new drug resistance mutations emerged within the study period

  Change from baseline to 9-month (window: 32-44 weeks) study visit

Study Arms (2)

Intervention

EXPERIMENTAL

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.

Other: Clinical management informed by HIV-1 genotypic resistance testing

Control

NO INTERVENTION

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.

Interventions

Clinical management informed by HIV-1 genotypic resistance testing 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.

Intervention

Eligibility Criteria

• Age: 6 Months - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Indication for treatment switch according to WHO guidelines at screening
• st 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
• Received a resistance test in the last 12 months

Sponsors & Collaborators

• Swiss Tropical & Public Health Institute: lead
• University Hospital, Basel, Switzerland: collaborator
• University of Basel: collaborator
• SolidarMed, Partnerships for Health: collaborator
• Seboche Mission Hospital: collaborator
• Ifakara Health Institute: collaborator
• Baylor College of Medicine Children's Foundation: collaborator

Study Sites (10)

Seboche Mission Hospital

Seboche, Butha-Buthe, Lesotho

Location

Baylor Clinic Leribe

Hlotse, Leribe District, Lesotho

Location

Baylor Clinic Butha-Buthe

Butha-Buthe, Lesotho

Location

Baylor Clinic Maseru

Maseru, Lesotho

Location

Baylor Clinic Mohale's Hoek

Mohale's Hoek, Lesotho

Location

Baylor Clinic Mokhotlong

Mokhotlong, Lesotho

Location

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

Ifakara, Morogoro, Tanzania

Location

Mbagala Rangi Tatu Hospital

Dar es Salaam, Tanzania

Location

Temeke Regional Referral Hospital

Dar es Salaam, Tanzania

Location

Upendano Dispensary

Dar es Salaam, Tanzania

Location

Related Publications (2)

• 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.

  PMID: 33076866 BACKGROUND

• 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.

  PMID: 39030062 RESULT

Related Links

• trial website

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Niklaus D Labhardt, MD, MIH

  Swiss Tropical & Public Health Institute

  STUDY CHAIR

• Jennifer A Brown, PhD

  Swiss Tropical & Public Health Institute

  PRINCIPAL INVESTIGATOR

• Thomas Klimkait, PhD

  University of Basel

  STUDY DIRECTOR

• Josephine Muhairwe, MD, MPH

  SolidarMed, Partnerships for Health

  STUDY DIRECTOR

• Buntshi P Kayembe, MD

  Baylor College of Medicine Children's Foundation Lesotho

  STUDY DIRECTOR

• Mosa M Hlasoa, MD

  Baylor College of Medicine Children's Foundation Lesotho

  STUDY DIRECTOR

• Isaac Ringera, MPH, RN

  SolidarMed, Partnerships for Health

  STUDY DIRECTOR

• Maja Weisser, MD

  Swiss Tropical & Public Health Institute

  STUDY DIRECTOR

• Ezekiel Luoga, MD

  Ifakara Health Institute

  STUDY DIRECTOR

• Tracy R Glass, PhD

  Swiss Tropical & Public Health Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-centre, open-label, parallel-group (1:1 allocation), superiority randomised clinical trial

Study Record Dates

• First Submitted: January 11, 2020
• First Posted: January 18, 2020
• Study Start: March 3, 2020
• Primary Completion: March 15, 2023
• Study Completion: July 8, 2023
• Last Updated: September 25, 2024

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share

Locations

LE (6); TA (4)