Genotype-Informed Versus Empiric Management of VirEmia

HIV-1-infection Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04233242
• Other study ID #: P001-20-1.4
• Secondary ID: REG-19-008ID 229
• Status: Completed
• Phase: N/A
• Start date: March 3, 2020
• Est. completion date: July 8, 2023

Study information

• Verified date: April 2023
• Source: Swiss Tropical & Public Health Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 286
• Est. completion date: July 8, 2023
• Est. primary completion date: March 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 19 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV-1-infection
• Viremia

Intervention

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

Locations

Country	Name	City	State
Lesotho	Baylor Clinic Butha-Buthe	Butha-Buthe
Lesotho	Baylor Clinic Leribe	Hlotse	Leribe
Lesotho	Baylor Clinic Maseru	Maseru
Lesotho	Baylor Clinic Mohale's Hoek	Mohale's Hoek
Lesotho	Baylor Clinic Mokhotlong	Mokhotlong
Lesotho	Seboche Mission Hospital	Seboche	Butha-Buthe
Tanzania	Mbagala Rangi Tatu Hospital	Dar Es Salaam
Tanzania	Temeke Regional Referral Hospital	Dar es Salaam
Tanzania	Upendano Dispensary	Dar Es Salaam
Tanzania	One-Stop Clinic and Chronic Diseases Clinic (CDCI) at St Francis Referral Hospital	Ifakara	Morogoro

Sponsors (7)

Lead Sponsor	Collaborator
Swiss Tropical & Public Health Institute	Baylor College of Medicine Children's Foundation, Ifakara Health Institute, Seboche Mission Hospital, SolidarMed, Partnerships for Health, University Hospital, Basel, Switzerland, University of Basel

Countries where clinical trial is conducted

Lesotho,  Tanzania, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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	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
Other	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
Primary	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	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
Secondary	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.	Within 36 weeks after baseline
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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

External Links

•   trial website