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| ID | Type | Description | Link |
|---|---|---|---|
| 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) | |
| 12-2020 | Other Identifier | Ifakara Health Institute Review Board (Tanzania) | |
| NIMR/HQ/R.8a/Vol. IX/3222 | Other Identifier | National Institute for Medical Research (Tanzania) | |
| TMDA0020/CTR/0003/03 | Other Identifier | Tanzania Medicines and Medical Devices Authority (Tanzania) |
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| Name | Class |
|---|---|
| University Hospital, Basel, Switzerland | OTHER |
| University of Basel | OTHER |
| SolidarMed, Partnerships for Health | UNKNOWN |
| Seboche Mission Hospital |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clinical management informed by HIV-1 genotypic resistance testing | Other | The study intervention will consist of the following components:
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion with death due to any cause | Proportion of participants confirmed dead during the follow-period among all participants enrolled. | Within 36 weeks after baseline |
| Proportion with HIV- or ART-related hospital admission of ≥24 hours duration |
| Measure | Description | Time Frame |
|---|---|---|
| Time to viral suppression | 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. | 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 | Study Director |
| Mosa M Hlasoa, MD | Baylor College of Medicine Children's Foundation | 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Seboche Mission Hospital | Seboche | Butha-Buthe | Lesotho | |||
| Baylor Clinic Leribe |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33076866 | Background | 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. | |
| 39030062 |
| Label | URL |
|---|---|
| trial website | View source |
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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.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 23, 2021 | Dec 4, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 28, 2022 | Nov 16, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
Not provided
Not provided
| UNKNOWN |
| Ifakara Health Institute | OTHER |
| Baylor College of Medicine Children's Foundation | OTHER |
Multi-centre, open-label, parallel-group (1:1 allocation), superiority randomised clinical trial
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|
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.
| Within 36 weeks after baseline |
| 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. | Within 36 weeks after baseline |
| 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. | At 9 months follow-up visit (window: 32-44 weeks) |
| Proportion lost to follow-up | Proportion of participants with no documented clinic visit at 9 months among all participants enrolled. | At 9 months follow-up visit (window: 32-44 weeks) |
| 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. | At 9 months follow-up visit (window: 32-44 weeks) |
| 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. | 6 months (window: 20-28 weeks) after the decision on onward treatment |
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). |
| Baseline and 9-month (window: 32-44 weeks) study visit |
| Proportion with new drug resistance mutations emerged within the study period | Proportion of participants with new drug resistance mutations emerged within the study period among all participants enrolled. | Change from baseline to 9-month (window: 32-44 weeks) study visit |
| Tracy R Glass, PhD |
| Swiss Tropical & Public Health Institute |
| Study Director |
| 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 |
| Result |
| 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. |
| 41793741 | Derived | Schonenberger CM, Haenggi K, Ringera IK, Luoga E, Bresser M, Mothobi B, Mokhele K, Sando D, Molatelle M, Thahane L, Mnzava D, Ndege R, Hlasoa MM, Kayembe BP, Muhairwe J, Glass TR, Klimkait T, Weisser M, Labhardt ND, Tschumi N, Brown JA. HIV drug resistance amongst children and adolescents with viraemia in Lesotho and Tanzania: a nested analysis in the GIVE MOVE trial. J Antimicrob Chemother. 2026 Mar 4;81(4):dkag070. doi: 10.1093/jac/dkag070. |
| D015229 |
| Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |