Clinical trial NCT05426421: Tolerability of Lopinavir Versus Dolutegravir for Children and Adolescents Living With HIV
Official title: Tolerability of Lopinavir Versus Dolutegravir for Children and Adolescents Living With HIV (LoDoCA): a Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV
Keywords: dolutegravir
lopinavir
children
adolescents
paediatric
adverse effects
tolerability
treatment satisfaction
insomnia
sleep
gastrointestinal
depression
human immunodeficiency virus
cohort
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
Collaborators: name: University Hospital, Basel, Switzerland
name: University of Basel
name: University of Zurich
name: Baylor International Pediatric AIDS Initiative
name: Lesotho Ministry of Health
name: Baylor College of Medicine Children's Foundation Lesotho
First posted: 2022-06-22
Enrollment: 258
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children and adolescents living with HIV, receiving treatment, and transitioning from ritonavir-boosted lopinavir-based to dolutegravir-based antiretroviral therapy in the context of the national rollout of dolutegravir.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sleep duration during monitoring period 3 (2-4 weeks post-transition) versus monitoring period 1 (0-2 weeks pre-transition)
timeFrame: [2-4 weeks post-transition] vs [0-2 weeks pre-transition]
measure: Change in treatment satisfaction, assessed using the HIV Treatment Satisfaction Questionnaire (HIVTSQ) change version (HIVTSQ-c)
timeFrame: 4 weeks post-transition
Secondary outcomes:
measure: Viral suppression rate among those with virological data
timeFrame: 6 months, 12 months, and 24 months after transition
measure: Engagement in care with viral suppression
timeFrame: 6 months, 12 months, and 24 months after transition
measure: Sleep duration during monitoring period 2 (0-2 weeks post-transition) versus monitoring period 1 (0-2 weeks pre-transition)
timeFrame: [0-2 weeks post-transition] vs [0-2 weeks pre-transition]
measure: Sleep fragmentation
timeFrame: [2-4 weeks post-transition] vs [0-2 weeks pre-transition], and [0-2 weeks post-transition] vs [0-2 weeks pre-transition]
measure: Treatment satisfaction after vs before transition, assessed using the HIVTSQ status version (HIVTSQ-s)
timeFrame: 4 weeks post-transition vs at transition
measure: Gastrointestinal symptoms after vs before transition, assessed using the Gastrointestinal Symptom Rating Scale adapted for protease inhibitors (GSRS-PI)
timeFrame: 4 weeks post-transition vs at transition
measure: Depressive symptoms after vs before transition, assessed using the Center for Epidemiological Studies Depression Scale for Children (CES-DC)
timeFrame: 4 weeks post-transition vs at transition
measure: Sleep outcomes after vs before transition, assessed using the Child Sleep Habits Questionnaire (CSHQ) or Adolescent Sleep Habits Questionnaire (ASHQ)
timeFrame: 4 weeks post-transition vs at transition
measure: Health-related quality of life after vs before transition, assessed using the KINDL questionnaire
timeFrame: 4 weeks post-transition vs at transition
Other outcomes:
measure: Proportion of participants with drug resistance among participants with viraemia while taking dolutegravir
timeFrame: until 24 months after transition
measure: Impact of drug resistance at time of transition on subsequent viral suppression
timeFrame: until 24 months after transition
Locations:
city: Maseru
country: Lesotho
facility: Baylor Center of Excellence Maseru
Study officials:
affiliation: University of Basel
name: Jennifer Brown, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor International Paediatric AIDS Initiative
name: Akash Devendra, MBChB
role: PRINCIPAL_INVESTIGATOR
References: