Tolerability of Lopinavir Versus Dolutegravir for Children and Adolescents Living With HIV (LoDoCA)
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| ClinicalTrials.gov Identifier: NCT05426421 |
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Recruitment Status :
Recruiting
First Posted : June 22, 2022
Last Update Posted : May 22, 2023
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| Condition or disease |
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| HIV |
Dolutegravir, an antiretroviral drug to treat HIV, has recently been rolled out on a large scale across much of Africa. With paediatric formulations becoming increasingly available, dolutegravir is set to replace ritonavir-boosted lopinavir as the core agent in paediatric treatment regimens in many countries. While both drugs are well-studied and highly effective, they reportedly differ with regards to their tolerability at least in adults, with ritonavir-boosted lopinavir typically associated with gastrointestinal adverse effects and dolutegravir mostly associated with neuropsychiatric adverse effects including insomnia. Resistance patterns also differ between these two treatment options. However, studies focusing specifically on the tolerability of and adverse effects associated with either drug in children and adolescents are scarce.
This prospective cohort study aims to i) compare treatment satisfaction, health-related quality of life, tolerability, and symptoms or side-effects associated with either drug option, ii) specifically compare sleep outcomes quantified through actigraphy with either drug option, and iii) provide observational evidence on virological outcomes in a resource-limited setting using a before-after design.
The study is conducted at several sites in Lesotho, southern Africa. It enrols children and adolescents <18 years of age who are taking ritonavir-boosted lopinavir-based therapy at enrolment and routinely due to transition to dolutegravir-based therapy as per the national roll-out plan. On the day of transitioning to dolutegravir as well as four weeks thereafter, participants will complete questionnaires on treatment satisfaction, gastrointestinal symptoms, depressive symptoms, and sleep habits. A subset of participants fulfilling additional inclusion criteria will additionally use actigraphy sensors to monitor sleep duration and sleep fragmentation; these individuals will have study visits two weeks before transition to dolutegravir to initiate actigraphy, at transition, as well as two and four weeks after transition, with questionnaires at all but the pre-transition visit and actigraphy (target: at least seven nights with high-quality data) between all visits. For all participants, medical records will be assessed and additional clinical and sociodemographic data collected. A viral load test will be done on the day of transitioning to dolutegravir, and subsequent routine viral load test results (every six months as per national guidelines) will be assessed. Dried blood spots will be taken at all visits, barring the pre-transition visit for those with actigraphy.
This study aims to inform the continued roll-out of dolutegravir replacing ritonavir-boosted lopinavir in paediatric antiretroviral therapy regimens, notably assessing the suitability of a one-size-fits-all approach and providing detailed information on tolerability and adverse effects of either regimen.
| Study Type : | Observational |
| Estimated Enrollment : | 500 participants |
| Observational Model: | Cohort |
| Time Perspective: | Prospective |
| Official Title: | Tolerability of Lopinavir Versus Dolutegravir for Children and Adolescents Living With HIV (LoDoCA): a Prospective Cohort Study |
| Actual Study Start Date : | July 11, 2022 |
| Estimated Primary Completion Date : | September 2023 |
| Estimated Study Completion Date : | January 2025 |
| Group/Cohort |
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No actigraphy
Participants will receive viral load testing at transition from LPV/r-based to DTG-based ART, and subsequent routine viral load data will be analysed. Questionnaires will be filled in and dried blood spots collected at transition and at four weeks. Medical history as well as clinical and socio-demographic data will be collected.
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With actigraphy
Participants will receive viral load testing at transition from LPV/r-based to DTG-based ART, and subsequent routine viral load data will be analysed. Baseline actigraphy data will be collected for two weeks prior to transition (actigraphy period 1), and for four weeks after transition (actigraphy period 2 from 0-2 weeks after transition; actigraphy period 3 from 2-4 weeks after transition). Sleep diaries will be filled in during all actigraphy periods. Questionnaires will be filled in and dried blood spots taken at transition as well as two and four weeks after transition. Medical history as well as clinical and socio-demographic data will be collected.
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- Sleep duration during monitoring period 3 (2-4 weeks post-transition) versus monitoring period 1 (0-2 weeks pre-transition) [ Time Frame: [2-4 weeks post-transition] vs [0-2 weeks pre-transition] ]Sleep will be monitored using actigraphy sensors for a subset of participants. There will be three sleep monitoring periods: 0-2 weeks before transition from ritonavir-boosted lopinavir- to dolutegravir-based antiretroviral therapy (period 1), 0-2 weeks after transition, and 2-4 weeks after transition). We will conduct a before-after analysis.
- Change in treatment satisfaction, assessed using the HIV Treatment Satisfaction Questionnaire (HIVTSQ) change version (HIVTSQ-c) [ Time Frame: 4 weeks post-transition ]10-item scale with each item scored from -3 to +3 (overall range -30 to +30), with higher scores indicating increases in treatment satisfaction
- Viral suppression rate among those with virological data [ Time Frame: 6 months, 12 months, and 24 months after transition ]Proportion of participants with a viral load <50 copies/mL among all participants with virological data
- Engagement in care with viral suppression [ Time Frame: 6 months, 12 months, and 24 months after transition ]Proportion of participants with a viral load <50 copies/mL among all participants
- Sleep duration during monitoring period 2 (0-2 weeks post-transition) versus monitoring period 1 (0-2 weeks pre-transition) [ Time Frame: [0-2 weeks post-transition] vs [0-2 weeks pre-transition] ]Sleep will be monitored using actigraphy sensors for a subset of participants. There will be three sleep monitoring periods: 0-2 weeks before transition from ritonavir-boosted lopinavir- to dolutegravir-based antiretroviral therapy (period 1), 0-2 weeks after transition, and 2-4 weeks after transition). We will conduct a before-after analysis.
- Sleep fragmentation [ Time Frame: [2-4 weeks post-transition] vs [0-2 weeks pre-transition], and [0-2 weeks post-transition] vs [0-2 weeks pre-transition] ]Sleep will be monitored using actigraphy sensors for a subset of participants. There will be three sleep monitoring periods: 0-2 weeks before transition from ritonavir-boosted lopinavir- to dolutegravir-based antiretroviral therapy (period 1), 0-2 weeks after transition, and 2-4 weeks after transition). We will conduct a before-after analysis.
- Treatment satisfaction after vs before transition, assessed using the HIVTSQ status version (HIVTSQ-s) [ Time Frame: 4 weeks post-transition vs at transition ]10-item scale with each item scored from 0 to 6 (overall range 0 to 60), with higher scores indicating higher treatment satisfaction. Two time points compared in a before-after analysis.
- Gastrointestinal symptoms after vs before transition, assessed using the Gastrointestinal Symptom Rating Scale adapted for protease inhibitors (GSRS-PI) [ Time Frame: 4 weeks post-transition vs at transition ]13-item scale with each item scored from 1 to 6, with higher scores indicating greater discomfort. Two time points compared in a before-after analysis.
- Depressive symptoms after vs before transition, assessed using the Center for Epidemiological Studies Depression Scale for Children (CES-DC) [ Time Frame: 4 weeks post-transition vs at transition ]20-item scale with each item scored from 0 to 3 (overall range 0 to 60), with higher scores indicating higher depressive symptoms. Two time points compared in a before-after analysis.
- Sleep outcomes after vs before transition, assessed using the Child Sleep Habits Questionnaire (CSHQ) or Adolescent Sleep Habits Questionnaire (ASHQ) [ Time Frame: 4 weeks post-transition vs at transition ]33-item scale (2 items used in two subscales) with each item scored from 1 to 3, with higher scores indicating more sleep problems. Two time points compared in a before-after analysis.
- Health-related quality of life after vs before transition, assessed using the KINDL questionnaire [ Time Frame: 4 weeks post-transition vs at transition ]24-item scale with each item scored from 1 to five, with higher scores indicating higher health-related quality of life
- Proportion of participants with drug resistance among participants with viraemia while taking dolutegravir [ Time Frame: until 24 months after transition ]Classified Stanford HIV drug resistance database (susceptible, potential low-level resistance, low-level resistance, intermediate resistance, high-level resistance) referring to each drug in the current ART regimen
- Impact of drug resistance at time of transition on subsequent viral suppression [ Time Frame: until 24 months after transition ]Assessment whether resistance at transition predicts subsequent routinely assessed viral load outcomes
Biospecimen Retention: Samples With DNA
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| Ages Eligible for Study: | up to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Sampling Method: | Non-Probability Sample |
Inclusion Criteria - general:
- Currently taking ritonavir-boosted lopinavir-containing antiretroviral therapy
- Eligible for dolutegravir-based antiretroviral therapy as per national roll-out/guidelines
- Age < 18 years
- Informed consent (as per consenting procedures)
Exclusion Criteria - general:
- No transition to dolutegravir-based antiretroviral therapy foreseen
- Already enrolled in another study judged as non-compatible by the Principal Investigator or Local Principal Investigator
Inclusion Criteria - actigraphy:
- Enrolled into main cohort
- Age ≥6 and <18 years
- Taking ritonavir-boosted lopinavir-containing antiretroviral therapy for at least 12 weeks
- Last viral load <50 copies/mL and taken within <36 weeks and while taking ritonavir-boosted lopinavir-containing antiretroviral therapy
- Willingness to wear an actimetry sensor every night for at least 7 nights (daytime wearing optional)
- Patient and/or caregiver judged to be able to fulfil requirements (wearing actimetry sensor; filling in sleep diary) by study team member conducting screening
- Stated ability to attend all study visits
- Informed consent (as per consenting procedures)
Exclusion Criteria - actigraphy:
- Intention to transfer out of the study site (and not into a different study site) within 6 weeks
- No actimetry sensor available
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): NCT05426421
| Contact: Jennifer Brown, PhD | +41 79 512 97 16 | jennifer.brown@unibas.ch | |
| Contact: Niklaus Labhardt, MD | n.labhardt@unibas.ch |
| Lesotho | |
| Baylor Center of Excellence Maseru | Recruiting |
| Maseru, Lesotho | |
| Contact: Akash Devendra, MD | |
| Baylor Satellite Center of Excellence Mohale's Hoek | Not yet recruiting |
| Mohale's Hoek, Lesotho | |
| Contact: Akash Devendra, MD | |
| Principal Investigator: | Jennifer Brown, PhD | University of Basel | |
| Principal Investigator: | Akash Devendra, MBChB | Baylor International Paediatric AIDS Initiative |
| Responsible Party: | Swiss Tropical & Public Health Institute |
| ClinicalTrials.gov Identifier: | NCT05426421 |
| Other Study ID Numbers: |
P001-22-1.0 ID37-2022 ( Other Identifier: National Health Research Ethics Committee (Lesotho) ) H-51472 ( Other Identifier: Institutional Review Board for Baylor College of Medicine and Affiliated Hospitals ) 3ZX1422 ( Other Grant/Funding Number: University of Basel Research Fund ) |
| First Posted: | June 22, 2022 Key Record Dates |
| Last Update Posted: | May 22, 2023 |
| Last Verified: | April 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | De-identified data will be shared in a data repository upon publication of results. |
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dolutegravir lopinavir children adolescents paediatric adverse effects tolerability |
treatment satisfaction insomnia sleep gastrointestinal depression human immunodeficiency virus cohort |