Clinical trial NCT04238767: Dolutegravir in Real Life in Lesotho
Official title: Observational Assessment of the Nation-wide Roll-out of Dolutegravir in Lesotho
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV-1-infection
Keywords: HIV-1
AIDS
dolutegravir
antiretroviral therapy
Lesotho
sub-Saharan Africa
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
Collaborators: name: SolidarMed
name: Ministry of Health, Lesotho
name: District Health Management Team of Butha-Buthe, Lesotho
name: District Health Management Team of Mokhotlong, Lesotho
name: University of Basel
First posted: 2020-01-23
Enrollment: 1433
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be enrolled at two government hospitals and one missionary hospital in two districts (Butha-Buthe and Mokhotlong) in Lesotho.

Brief summary: DO-REAL is an observational cohort study assessing the large-scale roll-out of the antiretroviral drug dolutegravir (DTG) in Lesotho.

DTG has been shown to have low side-effects and superior treatment outcomes for people living with HIV-1 when compared to other antiretroviral drugs currently in use in low-income countries. The use of DTG in first-line antiretroviral therapy (ART) regimens was recommended by the World Health Organisation in 2018 and adopted by the Ministry of Health in Lesotho in 2019. While DTG-based ART regimens have led to promising health outcomes in high-income and clinical trial settings, certain concerns remain regarding the risk of ART-experienced patients transitioning to a DTG-based ART regimen being placed on a functional monotherapy (increasing the otherwise low risk of viral resistance to DTG) as well as side-effects including psychological symptoms and weight gain.

Thus, the DO-REAL study intends to address these concerns and provide data on health outcomes of HIV patients on DTG in a "real-life" high-prevalence setting.

Detailed description: SUMMARY: DO-REAL is an observational cohort study assessing the large-scale roll-out of the antiretroviral drug dolutegravir (DTG) in Lesotho.

BACKGROUND: DTG is a second-generation integrase strand transfer inhibitor with low side-effects and superior treatment outcomes for people living with HIV-1 when compared to other antiretroviral drugs currently in use in low-income countries. Though some cases have been described, HIV-1 resistance to DTG is rare in clinical settings when DTG is used as part of a combination therapy. The use of DTG in first-line antiretroviral therapy (ART) regimens was recommended by the World Health Organisation in 2018 and was adopted by the Ministry of Health in Lesotho in 2019. DTG now forms part of the recommended first-line therapy for many ART-naïve patients in Lesotho. In addition, many patients on a non-DTG-based first-line ART regimen will be transitioned to a DTG-based regimen.

OBJECTIVES: Despite the positive health outcomes observed in patients receiving DTG-based ART in high-income countries and in clinical trial settings, there is little data on virologic outcomes of patients on DTG during large-scale implementation in low- and lower middle-income countries. Concerns remain regarding the risk that some patients transitioning to a DTG-based regimen will be placed on a functional monotherapy. Furthermore, there are concerns as to psychological side-effects and observed weight gain. This observational study aims to assess the virologic outcomes (viral suppression rates as well as potential drug resistance) as well as side-effects of people living with HIV-1 and transitioning to a DTG-based ART regimen in Lesotho.

DO-REAL has two major objectives:

* To assess virologic outcomes after the programmatic shift to DTG-based regimens.
* To assess psychological and somatic wellbeing in patients before and after the programmatic shift to DTG-based regimens.

METHODS: DO-REAL is a cohort study enrolling people living with HIV who are initiating or are eligible (according to national guidelines and the local implementation thereof) to initiate a DTG-based antiretroviral therapy (ART) regimen. The study will take place at three hospitals in two districts (Butha-Buthe, Mokhotlong) in Lesotho, and aims to enrol over 2000 participants. Viral loads will be measured on the day of initiating a DTG-based regimen (or on the day this was offered), as well as four, 12 and 24 months thereafter. In a post-hoc analysis, samples will be tested for drug resistance in samples where the viral load permits (approx. ≥100 c/mL). A subset of participants will complete screenings for depression, general health, and HIV-related symptoms.

Eligibility criteria: Inclusion Criteria:

* HIV-1-positive
* Initiating or eligible to initiate (offered to initiate) a DTG-based ART regimen
* Informed written consent (and assent, if applicable) provided

Exclusion Criteria:

* None

Primary outcomes:
measure: Virologic outcomes after programmatic transition to DTG-containing regimens
timeFrame: 4 months after initiation of a DTG-containing regimen
measure: Quality of life screening score (change from baseline)
timeFrame: Change between time of initiation of a DTG-containing ART regimen and 4 months thereafter
measure: Depression screening score (change from baseline)
timeFrame: Change between time of initiation of a DTG-containing ART regimen and 4 months thereafter
measure: HIV symptom screening score (change from baseline)
timeFrame: Change between time of initiation of a DTG-containing ART regimen and 4 months thereafter
Secondary outcomes:
measure: Virologic status at programmatic transition to DTG-containing regimens
timeFrame: On day of initiation of a DTG-containing regimen
measure: Viral drug resistance at programmatic transition to DTG-containing regimens
timeFrame: On day of initiation of a DTG-containing ART regimen
measure: Weight (change from baseline)
timeFrame: On day of initiation of a DTG-containing ART regimen and 4, 12 and 24 months thereafter
measure: Reasons for discontinuation of a DTG-containing regimen
timeFrame: Up to 24 months after enrolment
measure: Long-term virologic outcomes after programmatic transition to DTG-containing regimens
timeFrame: 12 and 24 months after initiation of a DTG-containing regimen
measure: Viral drug resistance after programmatic transition to DTG-containing regimens
timeFrame: 4, 12 and 24 months after initiation of a DTG-containing regimen
Other outcomes:
Locations:
city: Butha-Buthe
country: Lesotho
facility: Butha-Buthe Government Hospital
city: Butha-Buthe
country: Lesotho
facility: Seboche Mission Hospital
Study officials:
affiliation: Swiss Tropical & Public Health Institute
name: Niklaus D Labhardt, MD, MIH
role: STUDY_CHAIR
affiliation: University of Basel
name: Thomas Klimkait, PhD
role: STUDY_DIRECTOR
affiliation: SolidarMed
name: Josephine Muhairwe, MD, MPH
role: STUDY_DIRECTOR
affiliation: Swiss Tropical & Public Health Institute
name: Jennifer A Brown, MSc, MAS D&C
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brown JA, Nsakala BL, Mokhele K, Rakuoane I, Muhairwe J, Urda L, Amstutz A, Tschumi N, Klimkait T, Labhardt ND. Viral suppression after transition from nonnucleoside reverse transcriptase inhibitor- to dolutegravir-based antiretroviral therapy: A prospective cohort study in Lesotho (DO-REAL study). HIV Med. 2022 Mar;23(3):287-293. doi: 10.1111/hiv.13189. Epub 2021 Oct 10.
citation: Brown JA, Nsakala BL, Mokhele K, Rakuoane I, Muhairwe J, Glass TR, Amstutz A, Tschumi N, Belus JM, Klimkait T, Labhardt ND. Dolutegravir in real life: Self-reported mental and physical health outcomes after transitioning from efavirenz- to dolutegravir-based antiretroviral therapy in a prospective cohort study in Lesotho. HIV Med. 2023 Feb;24(2):153-162. doi: 10.1111/hiv.13352. Epub 2022 Jun 22.