DO-REAL - Observational Assessment of the Nation-Wide Roll-Out of Dolutegravir in Lesotho (Dolutegravir in Real Life 'DO-REAL study')

Background: Dolutegravir (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 Government of 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 whose last viral load was undetectable and performed within the last six months will be moved 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. While the Ministry of Health of Lesotho has selected a conservative approach, there is a small 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, observed weight gain, and potential teratogenic effects of DTG in early pregnancy. In this observational study, we intend 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.

Methods: DO-REAL is a cohort study enrolling people living with HIV who are eligible to receive a dolutegravir (DTG-) based antiretroviral therapy (ART) regimen according to the addendum to the national clinical guidelines of Lesotho on the use of antiretroviral therapy (2019). 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, as well as four, 12 and 24 months thereafter. In a post-hoc analysis, we will test for drug resistance in samples with a viral load of 100 c/mL or higher. Furthermore, a subset of participants will complete screenings for depression (PHQ-9), general health (SF-12), and HIV-related symptoms.

Project registration: clinicaltrials.gov/ct2/show/NCT04238767

Funding: Swiss National Science Foundation (PCEFP3_181355)

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Involved Regions: Africa
Involved Countries: Lesotho

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