Description of Real World Antiviral Effectiveness and Sustainability of the 2-Drug Regimen Dolutegravir + Lamivudine in Untreated and Pre-treated Patients in Routine Clinical Care in Germany

Study Overview
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Brief Summary
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This is a prospective, non-interventional, multi-center study, in subjects with clinical indication of Human Immunodeficiency Virus (HIV)-1 infection. The aim of the study is to generate the real world evidence for the use of DTG+3TC in routine clinical care in Germany to supplement data obtained from controlled clinical trials. Approximately, 300 treatment naïve and pre-treated HIV-1 positive subjects will be enrolled in the study. The observation period for the study will be 3 years. Data will be collected from routine clinical care via electronic data capture (EDC) system.

Official Title
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Description of Real World Antiviral Effectiveness and Sustainability of the 2-Drug Regimen Dolutegravir + Lamivudine in Untreated and Pre-treated Patients in Routine Clinical Care in Germany

Conditions
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HIV Infections

Intervention / Treatment
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* Other: HIV Symptom Distress Module Questionnaire
* Other: HIV treatment satisfaction questionnaire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with >= 18 years of age. Subjects with documented HIV-1 infection. Prescription of DTG + 3TC was issued independently from entering this study. Subjects with the ability to understand informed consent form and other relevant regulatory documents. Exclusion Criteria: Any contraindication according to Tivicay or Lamivudine summaries of product characteristics (SmPCs). Subjects with VL > 500 c/mL. Any antiretroviral therapy for the treatment of HIV-1 in addition to DTG and 3TC or the DTG/3TC fixed dose combination (FDC). Subjects with hepatitis B virus (HBV)- coinfection. Subjects with current participation in the ongoing non-interventional study TRIUMPH (study number: 202033, NCT number: NCT02342769) or in any interventional clinical trial irrespective of indication. Subjects who had previously participated in clinical trials assessing DTG+ 3TC.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Treatment naïve subjects with HIV infection<br>Treatment naïve HIV-1 positive subjects for whom DTG+3TC is indicated according to local label will be included | Other: HIV Symptom Distress Module Questionnaire<br>* The Symptom Distress Module is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment.<br>Other: HIV treatment satisfaction questionnaire<br>* The HIV TSQ is a 10-item-self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience and flexibility.<br>|
| Pre-treated subjects with HIV infection<br>Pre-treated HIV-1 positive subjects for whom DTG+3TC is indicated according to local label will be included. | Other: HIV Symptom Distress Module Questionnaire<br>* The Symptom Distress Module is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment.<br>Other: HIV treatment satisfaction questionnaire<br>* The HIV TSQ is a 10-item-self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience and flexibility.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with sustained virologic suppression, with Viral load (VL) < 50 Copies per Milliliter (c/mL) | Percentage of subjects with sustained virologic suppression, defined as VL <50 c/mL or if between 50-200 c/mL with a subsequent next available measurement <50 c/mL (within 120 days) will be evaluated. | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of pre-treated subjects with low level viremia | Percentage of subjects with low level viremia, defined as a VL measurement between >50 to <200 c/mL for pre-treated subjects will be evaluated. | Up to 36 months | 
| Percentage of naïve subjects with low level viremia after initial suppression | Percentage of subjects with low level viremia, defined as a VL measurement between >50 to <200 c/mL after initial suppression of <50 c/mL for naïve subjects will be evaluated. | Up to 36 months | 
| Percentage of virologic non-responders for naïve subjects | Percentage of virologic non-responders, defined as two consecutive measurements >=200 c/mL after at least 24 weeks of treatment in naïve subjects will be evaluated. | Up to 36 months | 
| Percentage of naïve subjects with virologic rebound | Percentage of naïve subjects with virologic rebound, defined as two consecutive VL measurements >=200 c/mL after suppression (one VL <50 c/mL) will be evaluated. | Up to 36 months | 
| Percentage of subjects with VL < 50 c/mL | Percentage of subjects with VL <50 c/mL will be evaluated. | Up to 36 months | 
| Percentage of subjects with two consecutive VL measurements of >=200 c/mL | Percentage of subjects with two consecutive VL measurements of >=200 c/mL will be evaluated. | Up to 36 months | 
| Percentage of subjects with treatment switch | Percentage of subjects with treatment switch due to virologic failure (VF) or due to intolerability determined at the discretion of the physician will be evaluated. | Up to 36 months | 
| Percentage of subjects with VL > 50 c/mL with emergent resistance mutations | Percentage of subjects with VL >50 c/mL with emergent resistance mutations will be summarized. Resistance analysis will be performed at the physician's discretion. | Up to 36 months | 
| Number of monitoring measures | Number of monitoring measures (normalized to subject years) will be summarized. | Up to 36 months | 
| Number and frequency of serious adverse events (SAE) | An SAE is any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. | Up to 36 months | 
| Number and frequency of adverse drug reactions (ADRs) | An ADR is defined as a noxious and unintended response to a medicinal investigational product related to any dose where at least a reasonable possibility, that is the relationship cannot be ruled out. | Up to 36 months | 
| Adherence to therapy | Adherence to therapy will be determined from the number of monthly doses missed. | Up to 36 months | 
| Change from Baseline for lipid laboratory parameter: lactate dehydrogenase (LDH) | Lipid laboratory parameter LDH data will be evaluated at indicated time points. | Baseline and up to 36 months | 
| Change from Baseline for lipid laboratory parameters: cholesterol and triglycerides | Lipid laboratory parameters cholesterol and triglycerides data will be evaluated at indicated time points. | Baseline and up to 36 months | 
| Change in treatment satisfaction based on HIV Treatment Satisfaction questionnaire (HIV TSQ) | The HIV TSQ is a 10-item-self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience and flexibility. In treatment satisfaction score will range from 0-60, higher the score, greater the satisfaction with treatment. Individual item scores which included All rate score ranging from 0 (very dissatisfied, inconvenient, inflexible) to 6 (very satisfied, convenient, flexible), in case of general satisfaction , there will be 10 items which will be summed to produce a score ranging from 0 to 30, with higher the score greater the satisfaction with subscale. For lifestyle scale with 8 items which will be summed to produce a score ranging from 0 to 30, with higher the score greater the satisfaction with subscale. | Up to 36 months | 
| Change in Symptom Distress based on HIV Symptom Distress Module questionnaire | The Symptom Distress Module is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. This included sub-scales change in treatment satisfaction, individual satisfaction with treatment change. Treatment satisfaction score summed all items to produce scores ranging from +30 to -30, higher the score, greater the improvement in satisfaction with treatment, lower score greater is the deterioration in satisfaction. Individual item scores which included All rate score ranging from +3 (much more satisfied, much more convenient, much more flexible) to -3 (much less satisfied, much less convenient, much less flexible). General satisfaction and life style scores all items summed to produce score range +15 to -15, where higher the score greater the improvement in satisfaction, lower score greater is the deterioration in satisfaction. | Up to 36 months | 
| Reasons for switching to/prescription of DTG plus 3TC | The reasons for switching to/prescription of DTG plus 3TC as selected by the investigator from a pre-specified list will be summarized | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dolutegravir, Two-drug regimen, Human Immunodeficiency Virus, HIV Symptom Distress Module, Lamivudine, HIV treatment satisfaction questionnaire