Tolerability of Lopinavir Versus Dolutegravir for Children and Adolescents Living With HIV

NCT ID: NCT05426421

Last Updated: 2025-01-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 258 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-07-11
• Study Completion Date: 2023-09-20

Brief Summary

Dolutegravir-based antiretroviral therapy is set to be increasingly replace ritonavir-boosted lopinavir-based regimens for the treatment of paediatric HIV. This prospective cohort study aims to compare tolerability, adverse effects, and virological outcomes between the two regimen types using a before-after design. The study is conducted in Lesotho, southern Africa, and includes children and adolescents transitioning from ritonavir-boosted lopinavir-based to dolutegravir-based antiretroviral therapy. It aims to provide detailed information on treatment tolerability and to inform paediatric treatment programmes.

Detailed Description

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.

Conditions

HIV

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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)

• 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

• 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

• Intention to transfer out of the study site (and not into a different study site) within 6 weeks
• No actimetry sensor available

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: collaborator

University of Basel

OTHER

Sponsor Role: collaborator

University of Zurich

OTHER

Sponsor Role: collaborator

Baylor International Pediatric AIDS Initiative

UNKNOWN

Sponsor Role: collaborator

Lesotho Ministry of Health

UNKNOWN

Sponsor Role: collaborator

Baylor College of Medicine Children's Foundation Lesotho

UNKNOWN

Sponsor Role: collaborator

Swiss Tropical & Public Health Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer Brown, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Basel

Akash Devendra, MBChB

Role: PRINCIPAL_INVESTIGATOR

Baylor International Paediatric AIDS Initiative

Locations

Baylor Center of Excellence Maseru

Maseru, , Lesotho

Countries

Lesotho

Other Identifiers

ID37-2022

Identifier Type: OTHER

Identifier Source: secondary_id

H-51472

Identifier Type: OTHER

Identifier Source: secondary_id

3ZX1422

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

P001-22-1.0

Identifier Type: -

Identifier Source: org_study_id