Clinical trial NCT04568239: Impact of M184V on the Virological Efficacy to 3TC/DTG (LAMRES)
Official title: Impact of M184V on the Virological Efficacy to Lamivudine/Dolutegravir
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV-1-infection
Lead sponsor: Association de Recherche en Virologie et Dermatologie
Sponsor class: OTHER
First posted: 2020-09-29
Enrollment: 712
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV-1-infected patients with (i) age ≥18 years, (ii) HIV-RNA ≤50 copies/mL on any ART regimen, (iii) subsequently switching to DTG/3TC, (iv) with at least 1 previous plasma HIV-1 RNA or HIV-DNA genotype, (v) with at least 1 virological and clinical follow-up after switching to DTG/3TC.

The occurrence of M184V will be assessed using historical genotypic resistance tests; that is, any detection of this mutation in any previous resistance test will be scored as positive.

Brief summary: In view of the prolongation of patients living with HIV's life expectancy, the question of optimization of ART, which is still a life-long treatment, becomes central. While most patients achieve virological success, their treatments often need to be optimized in order to limit adverse events, drugs interactions and to improve adherence. The switch to dual regimen strategies represent one of the approaches for treatment optimization. Indeed, dual therapy regimens have shown non-inferior efficacy vs triple therapy as simplification therapy and more recently also as first line therapy. From the real-life data it emerges that today in simplification strategies, the dual regimen therapies are prescribed even in patients with a history of virological failure. Circulating HIV-1 resistant variants can be archived in viral reservoirs, where they can persist for years and can reemerge in case of therapeutic selective pressure. In particular, previous selection of M184V may have an impact on virological response to 3TC/DTG. There are few data on a direct comparison of 3TC/DTG efficacy in patients harboring or not harboring the M184V. So, there is a need to assess the efficacy of 3TC/DTG in patients with past M184V mutation in a large set of patients followed in clinical setting.

Thus, the investigators propose a retrospective study of patients with HIV-RNA ≤50 copies/mL who were switched to 3TC/DTG in order to compare the virological efficacy of 3TC/DTG in patients with and without a history of M184V detection in a previous resistance genotype. This study aimed to analyze 800 patients switched to DTG/3TC in clinical real setting in large European (France, Italy, Spain) database.


Eligibility criteria: Inclusion Criteria:

* HIV-1 infected
* Age ≥ 18 years
* Switched to 3TC/DTG while having HIV-RNA ≤50 copies/mL on any ART regimen
* Followed for at least 1 year after 3TC/DTG switch
* With at least 1 previous genotype
* With at least 1 virological follow-up after switching to 3TC/DTG

Exclusion Criteria:

* No genotypic resistance test available before switching to DTG/3TC

Primary outcomes:
measure: probability of virological failure
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: ARVD
Study officials:
affiliation: Sorbonne University; APHP
name: Anne-Genevieve Marcelin, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
References: