HIV A6 Genome In ART Unsuccessful Patients On DOR

• Conditions: Virus-HIV
• Interventions: Drug: Doravirine

• Registration Number: NCT05322083
• Lead Sponsor: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation

Brief Summary

The aim of the study is to evaluate the efficacy of Doravirine (DOR) in the second-line therapy for patients infected with HIV-1 sub-subtype A6 and its derivatives and having the mutations to previously used drugs

Detailed Description

During the study 60-80 HIV-infected patients in 2-4 investigation sites (AIDS Centers) across Russia with proven virological failure on first-line antiretroviral therapy (ART) including efavirenz (EFV) and nevirapine (NVP) will be enrolled. The blood samples, epidemiological, clinical and demographic data of patients participating in the study must be collected. All participants must provide written informed consent before the start of the study.

Virological failure on NNRTI regimen in all the participants will be confirmed by HIV genotyping. All the patients with confirmed NNRTI mutations will be switched to DOR instead of EFV/NVP in the second-line therapy and enrolled to the study.

The primary efficacy endpoints of ART with DOR will be weeks 8 and 24 (viral load + T-cell count). For all samples with virological failure at weeks 8 or 24 HIV-1 DNA sequences (full protease (PR) and partial reverse transcriptase (RT) regions) will be obtained using the in-house test system or commercial kit (Central Research Institute of Epidemiology, Moscow, Russia). In case of virological failure of DOR treatment, the analysis of drug resistance mutations will be carried out.

Study Timeline

• Study First Submitted: 2022-03-22
• Status Verified: 2022-04
• Study First Submitted QC: 2022-04-04
• Last Update Submitted: 2022-04-04
• Study First Posted: 2022-04-11
• Last Update Posted: 2022-04-11
• Study Start: 2022-05
• Primary Completion: 2023-05
• Study Completion: 2024-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• HIV-infection confirmed
• > 18 years
• Informed consent signed

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Exclusion Criteria

• Pregnant women

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
HIV patients	Doravirine	All patients will be prescribed treatment drugs in accordance with the national protocol by the doctors of the AIDS centers. The decision to prescribe Doravirine will also be made by doctors.

Primary Outcome Measures

Name	Time	Method
HIV viral load	Week 24	The result of measuring the HIV viral load 24 weeks after the start of DOR-based treatment. The success of therapy will correspond to an undetectable level of viral load (less than 50 RNA copies/ml). Upon receipt of any detected viral load, the treatment will be considered a failure and the reasons for the failure (lack of adherence, drug interactions, non-compliance with dietary requirements, etc.) will be analyzed. If these causes are excluded, the HIV genotype will be analyzed for the presence of drug resistance mutations (RT genome region).

Secondary Outcome Measures

Name	Time	Method
HIV genotype	Week 24	HIV genotype in patients experienced failure on DOR-based treatment regimen (RT genome region). The study of the genotype will make it possible to understand to which of the components of the therapy regimen the virus has developed resistance and which of the drugs needs to be replaced. If it turns out to be a drug from the basic regimen (not DOR but NRTIs), the regimen will be changed at the discretion of the attending physician (this decision is not within the scope of this project). If DOR resistance mutations are detected such as V106I or Y188L, their frequency will be estimated (the proportion of patients with such mutations ) and the spectrum of associated mutations will be analysed.