Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04233242
Recruitment Status : Recruiting
First Posted : January 18, 2020
Last Update Posted : April 7, 2020
Sponsor:
Collaborators:
University Hospital, Basel, Switzerland
University of Basel
SolidarMed, Partnerships for Health
Baylor College of Medicine Children's Foundation
Seboche Mission Hospital
Ifakara Health Institute
Information provided by (Responsible Party):
Swiss Tropical & Public Health Institute

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. If the viral load remains high, the ART regimen is adjusted according to empirical guidelines; if not, the participant remains on an unchanged ART regimen. The intervention arm receives GRT and GRT-informed onward therapy; that is, in the case of drug resistance, the ART regimen is adjusted as appropriate, whereas if no (relevant) drug resistance is detected, there is no change of ART regimen. 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.


Condition or disease Intervention/treatment Phase
HIV-1-infection Other: Clinical management informed by HIV-1 genotypic resistance testing Not Applicable

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 (min. 4 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 while on first-line ART 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. A sustained viral load ≥400 c/mL triggers a switch to an empirically selected second-line ART regimen (according to national clinical guidelines); if the second viral load is <400 c/mL, the participant's ART regimen remains unchanged.

In the intervention arm, participants receive GRT (Sanger sequencing) 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 276 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multi-centre, open-label, parallel-group (1:1 allocation), superiority randomised clinical trial
Masking: None (Open Label)
Primary Purpose: Diagnostic
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
Actual Study Start Date : March 3, 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Intervention
The viral load ≥400 c/mL before enrolment triggers genotypic resistance testing (GRT), followed by GRT-informed patient management and counselling. If drug resistance mutations are present, the participant is switched to a different drug regimen line (or the drug regimen backbone is optimised) and drug selection is informed by the GRT result; if no drug resistance mutations are present, the current drug regimen is maintained and the patient receives targeted enhanced adherence support.
Other: 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.

No Intervention: 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. If the viral load remains ≥400 c/mL, the participant is switched to a different regimen line with drug selection based on empiric guidelines; if the viral load drops to <400 c/mL, the current drug regimen is maintained. The follow-up viral load test may be postponed in favour of additional counselling if there is clear evidence of poor adherence to therapy, defined as i) a pill count of <90%, and/or ii) a self-reported period of no drug intake of ≥2 days in the last 4 weeks.



Primary Outcome Measures :
  1. Composite primary endpoint [ Time Frame: At 9 months follow-up visit (window: 32-44 weeks) ]
    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 :
  1. Proportion with death due to any cause [ Time Frame: Within 36 weeks after baseline ]
    Proportion of participants confirmed dead during the follow-period among all participants enrolled.

  2. Proportion with HIV- or ART-related hospital admission of ≥24 hours duration [ Time Frame: Within 36 weeks after baseline ]
    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.

  3. Proportion with new clinical WHO stage IV event(s) (with some exclusions) [ Time Frame: Within 36 weeks after baseline ]
    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.

  4. Proportion without documentation of a suppressed viral load [ Time Frame: At 9 months follow-up visit (window: 32-44 weeks) ]
    Proportion of participants without documentation of viral load <50 c/mL at 9 months among all participants enrolled.

  5. Proportion lost to follow-up [ Time Frame: At 9 months follow-up visit (window: 32-44 weeks) ]
    Proportion of participants with no documented clinic visit at 9 months among all participants enrolled.

  6. Proportion with observed virologic failure [ Time Frame: At 9 months follow-up visit (window: 32-44 weeks) ]
    Proportion of participants with a viral load ≥50 c/mL among all participants with a viral load result at 9 months.

  7. Composite endpoint [ Time Frame: 6 months (window: 20-28 weeks) after the decision on onward treatment ]
    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.


Other Outcome Measures:
  1. Time to viral suppression [ Time Frame: 3- (window: 10-14 weeks), 6- (window: 20-28 weeks), and 9-month (window: 32-44 weeks) study visit ]
    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.

  2. 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 [ Time Frame: Baseline and 9-month (window: 32-44 weeks) study visit ]
    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).

  3. Proportion with new drug resistance mutations emerged within the study period [ Time Frame: Change from baseline to 9-month (window: 32-44 weeks) study visit ]
    Proportion of participants with new drug resistance mutations emerged within the study period among all participants enrolled.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Months to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • In care in a study site
  • Age ≥6 months and <19 years
  • Latest HIV viral load result ≥400 c/mL
  • On a first-line ART regimen (regimen has never been changed due to virologic failure)
  • On an unchanged ART regimen for ≥6 months
  • Phlebotomy for latest viral load test <3 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04233242


Contacts
Layout table for location contacts
Contact: Niklaus D Labhardt, MD, MIH +41 61 328 55 24 n.labhardt@swisstph.ch
Contact: Jennifer A Brown, MSc, MAS D&C +41 61 207 09 80 jennifer.brown@swisstph.ch

Locations
Layout table for location information
Lesotho
Baylor Clinic Leribe Recruiting
Hlotse, Leribe, Lesotho
Contact: Isaac Ringera, MPH, RN    +266 5677 1018    i.ringera@solidarmed.ch   
Baylor Clinic Butha-Buthe Recruiting
Butha-Buthe, Lesotho
Contact: Isaac Ringera, MPH, RN    +266 5677 1018    i.ringera@solidarmed.ch   
Baylor Clinic Mokhotlong Recruiting
Mokhotlong, Lesotho
Contact: Isaac Ringera, MPH, RN    +266 5677 1018    i.ringera@solidarmed.ch   
Tanzania
One-Stop Clinic and Chronic Diseases Clinic (CDCI) at St Francis Referral Hospital Not yet recruiting
Ifakara, Morogoro, Tanzania
Contact: Ezekiel Luoga, MD    +255 768 351 248    eluoga@ihi.or.tz   
Sponsors and Collaborators
Swiss Tropical & Public Health Institute
University Hospital, Basel, Switzerland
University of Basel
SolidarMed, Partnerships for Health
Baylor College of Medicine Children's Foundation
Seboche Mission Hospital
Ifakara Health Institute
Investigators
Layout table for investigator information
Study Chair: Niklaus D Labhardt, MD, MIH Swiss Tropical & Public Health Institute
Principal Investigator: Jennifer A Brown, MSc, MAS D&C Swiss Tropical & Public Health Institute
Study Director: 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
Layout table for additonal information
Responsible Party: Swiss Tropical & Public Health Institute
ClinicalTrials.gov Identifier: NCT04233242    
Other Study ID Numbers: P001-20-1.3
REG-19-008 ( Other Grant/Funding Number: Fondation Botnar )
ID 229-2019 ( Other Identifier: National Health Research Ethics Committee (Lesotho) )
Req-2019-01275 ( Other Identifier: Ethikkommission Nordwest- und Zentralschweiz (Switzerland) )
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: April 7, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Swiss Tropical & Public Health Institute:
HIV-1
acquired immunodeficiency syndrome
drug resistance
treatment failure
child
adolescent
Lesotho
Tanzania
Additional relevant MeSH terms:
Layout table for MeSH terms
Viremia
Virus Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes