Dolutegravir-based Dual Therapies in HIV-infected Patients With Virological Suppression

Study Overview
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Brief Summary
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The objective of this study was to evaluate the efficacy and safety, and evolution of causes leading to change, of dual therapies based in Dolutegravir in patients requiring a change of virologically effective antiretroviral therapy.

Detailed Description
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Despite the high rate of virological suppression and low risk of toxicity, HIV-infected patients continue to need new antiretroviral strategies, such as dual therapies, because of different end-organ involvement (kidney, bone, cardiovascular..), intolerance or toxicity. To date, only a protease inhibitor (PI)-based regimen was able to permit the use of dual therapies (two antiretrovirals), especially in case of patients with history of virological failure to other regimens. However, the recent license of Dolutegravir, a integrase inhibitor with high genetic barrier, could help to clinicians to manage patients with intolerance or toxicity to nucleoside analogues without putting in risk virological suppression.

Official Title
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The Efficacy and Safety of Dolutegravir-based Dual Therapies in HIV-infected Patients With Intolerance or Toxicity to Nucleoside Analogues

Conditions
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HIV Infection

Intervention / Treatment
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* Other: Dolutegravir in a dual therapy regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Older than 18 years Receiving a virologically effective antiretroviral regimen Switching to a dual therapy based in dolutegravir because of intolerance or toxicity to nucleoside analogues Exclusion Criteria: Pregnant women Receiving other investigational drugs Recent diagnosis of opportunistic infection (< 1 month)

Ages Eligible for Study
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Minimum Age: 18 Years

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

| Intervention/Treatment |
| --- |
|Other: Dolutegravir in a dual therapy regimen|None. Patients initiating Dolutegravir-based dual therapy because of nucleoside analogues toxicity or intolerance will be followed up during a year|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy, measured as maintenance of virological suppression, after switching to a dolutegravir-based dual therapy | Percent of patients remaining with HIV RNA level below 50 copies/ml, according to a missing=failure criteria | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety according to DAIDS grade events 2009 of dual therapy based in dolutegravir | To collect adverse events (according to DAIDS grade events, 2009) and rate of discontinuation related with adverse events, of dual therapy after switching | 12 months | 
| Outcome of causes leading to switch the previous regimen | Evolution of causes de change: glomerular filtration rate during evolution, tubular dysfunction (proteinuria, phosphaturia, glycosuria, uricosuria),bone mineral density by DXA (dual X-ray absorptiometry), lipid disorders, adherence | 12 months | 
| Efficacy, measured as maintenance of virological suppression, of different dual therapies with dolutegravir | Comparison of efficacy (HIV RNA level < 50 c/ml) of the different dolutegravir-based dual therapies, according to accompanying drug (non nucleoside, especially rilpivirine), protease inhibitors (darunavir boosted with ritonavir or cobicistat), or nucleoside analogues (lamivudine). | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, dolutegravir, intolerance, dual therapies