Dolutegravir in Real Life in Lesotho

Study Overview
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Brief Summary
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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
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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.

Official Title
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Observational Assessment of the Nation-wide Roll-out of Dolutegravir in Lesotho

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Dolutegravir


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV-1-positive individuals<br>HIV-1-positive individuals eligible to receive a DTG-based ART regimen at enrolment. | Drug: Dolutegravir<br>* Eligibility to receive DTG-based ART at enrolment (i.e., initiation or offer to initiate DTG-based ART)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic outcomes after programmatic transition to DTG-containing regimens | Viral load | 4 months after initiation of a DTG-containing regimen | 
| Quality of life screening score (change from baseline) | 12-Item Short Form Health Survey (SF-12; 12-item index in which questions are scored and weighted into 2 subscales, physical health and mental health; scores can range from 0-100 with higher scores indicating higher physical or mental health) | Change between time of initiation of a DTG-containing ART regimen and 4 months thereafter | 
| Depression screening score (change from baseline) | Patient Health Questionnaire-9 (PHQ-9; 9-item index with each item scored 0-3, providing a 0-27 severity score with a higher score indicating higher severity) | Change between time of initiation of a DTG-containing ART regimen and 4 months thereafter | 
| HIV symptom screening score (change from baseline) | Modified HIV Symptom Index (21-item index with each item scored 0-4, providing a 0-84 severity score with a higher score indicating higher severity) | Change between time of initiation of a DTG-containing ART regimen and 4 months thereafter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic status at programmatic transition to DTG-containing regimens | Viral load (post-hoc analysis) | On day of initiation of a DTG-containing regimen | 
| Viral drug resistance at programmatic transition to DTG-containing regimens | HIV-1 drug resistance (assessed by Sanger sequencing) in the case of an unsuppressed viral load (post-hoc analysis) | On day of initiation of a DTG-containing ART regimen | 
| Weight (change from baseline) | Change from time of enrolment; median and interquartile range; in kg | On day of initiation of a DTG-containing ART regimen and 4, 12 and 24 months thereafter | 
| Reasons for discontinuation of a DTG-containing regimen | Reasons for discontinuing a DTG-containing regimen as noted in medical records, where applicable | Up to 24 months after enrolment | 
| Long-term virologic outcomes after programmatic transition to DTG-containing regimens | Viral load | 12 and 24 months after initiation of a DTG-containing regimen | 
| Viral drug resistance after programmatic transition to DTG-containing regimens | HIV-1 drug resistance (assessed by Sanger sequencing) in the case of an unsuppressed viral load | 4, 12 and 24 months after initiation of a DTG-containing regimen | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, AIDS, dolutegravir, antiretroviral therapy, Lesotho, sub-Saharan Africa