Impact of DOlutegravir+Lamivudine Simplification on HIV-1 Reservoirs

Study Overview
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Brief Summary
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For a few years, there has been a keen interest of clinicians and patients for lighter antiretroviral strategies based on two- or even single drug regimens rather than the canonical triple therapy, both as initial and maintenance therapy, despite the possibility that ongoing viral replication may occur in some patients under triple-therapy. We will therefore propose such simplification strategy (DTG/3TC) while maintaining triple-therapy (DTG/ABC/3TC) in a control group and will perform an in depth analysis of the replication-competent reservoir in blood and in tissues as well as measurements of residual viremia and immune chronic activation/inflammation.

Official Title
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Impact of DOlutegravir+Lamivudine Simplification on TIssue and Blood Latent Replication-competent HIV-1 Reservoirs (IDOLTIB Study)

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Treatment simplification (dolutegravir lamivudine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-infected adults receiving cART for at least 2 years DTG/3TC/ABC as cART regimen in the previous 6 months. CD4 counts higher than 200 cells per μL and virological suppression for at least 2 years (plasma HIV RNA <20 copies per mL) Exclusion Criteria: hepatitis C or B co-infection unstable liver disease renal impairment (estimated glomerular filtration rate <50 mL per min), gastrointestinal disorders that would affect the absorption of study treatment current use of drugs with significant interactions with dolutegravir current use of drugs with an impact on inflammation such as steroids. hospitalization for acute illness within the previous 8 weeks Pregnancy or breastfeeding. Known resistance to DTG or 3TC Active tuberculosis Anal or rectal lesions impeding rectal biopsies Decreased platelets count or coagulation disorder.

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2DR<br>Switch from 3 drug regimen (DTG+ABC+3TC) to 2 drug regimen (DTG+3TC) | Drug: Treatment simplification (dolutegravir lamivudine)<br>* Switch from 3 drug regimen (DTG/ABC/3TC) to 2 drug regimen<br>|
| No Intervention: 3DR<br>Continued 3 drug regimen treatment (DTG+ABC+3TC) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The impact of dual-therapy Dolutegravir (DTG) + Lamivudine (3TC) at the level of replication-competent reservoir (RCR) in blood and in tissues. | Measurements of RCR in the blood and tissues (rectal biopsies) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The impact of dual-therapy Dolutegravir (DTG) + Lamivudine (3TC) on residual viremia. |  | 1 year | 
| The impact of dual-therapy Dolutegravir (DTG) + Lamivudine (3TC) at the level of chronic immune activation/inflammation. |  | 1 year | 
| The correlation between blood and tissues RCR in a high number of patients under suppressive antiretroviral therapy. |  | 1 year | 
| The level of clonal expansion in the blood and tissue RCR |  | 1 year | 
| The correlation between the size of the blood/tissues RCR and the level of chronic immune activation/inflammation. |  | 1 year |