HIV A6 Genome In ART Unsuccessful Patients On DOR

Virus-HIV Clinical Trial

— HIV-A6-DOR  

Official title:

Analysis of HIV Subtype A6 Genome in Patients With Virological Failure After Switching to Doravirine (DOR)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05322083
• Other study ID #: MISP#60102
• Status: Not yet recruiting
• Start date: May 2022
• Est. completion date: January 2024

Study information

• Verified date: April 2022
• Source: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
• Contact: Marina Bobkova, DrSci
• Phone: +79163138387
• Email: mrbobkova[@]mail.ru
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: January 2024
• Est. primary completion date: May 2023
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV-infection confirmed

• > 18 years

• Informed consent signed

Exclusion Criteria:

• Pregnant women

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Virus-HIV

Intervention

Drug:
• Doravirine
Doravirine will be given to patients after failure on the first NNRTI regimen.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation	MSD Pharmaceuticals LLC

References & Publications (4)

Ayitewala A, Kyeyune F, Ainembabazi P, Nabulime E, Kato CD, Nankya I. Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. AIDS Res Ther. 2020 Jan 31;17(1):2. doi: 10.1186/s12981-020-0258-7. — View Citation

Baryshev PB, Bogachev VV, Gashnikova NM. Genetic characterization of an isolate of HIV type 1 AG recombinant form circulating in Siberia, Russia. Arch Virol. 2012 Dec;157(12):2335-41. doi: 10.1007/s00705-012-1442-4. Epub 2012 Aug 19. — View Citation

Lapovok I, Laga V, Kazennova E, Bobkova M. HIV Type 1 Integrase Natural Polymorphisms in Viral Variants Circulating in FSU Countries. Curr HIV Res. 2017 Nov 23;15(5):318-326. doi: 10.2174/1570162X15666170815162052. — View Citation

Venner CM, Nankya I, Kyeyune F, Demers K, Kwok C, Chen PL, Rwambuya S, Munjoma M, Chipato T, Byamugisha J, Van Der Pol B, Mugyenyi P, Salata RA, Morrison CS, Arts EJ. Infecting HIV-1 Subtype Predicts Disease Progression in Women of Sub-Saharan Africa. EBi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HIV viral load	The result of measuring the HIV viral load 8 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) or a decrease of two logarithms compared with the values before treatment start. Upon receipt of a detected viral load, treatment will be nevertheless continued up to 24 weeks.	Week 8
Primary	HIV viral load	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).	Week 24
Secondary	HIV genotype	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.	Week 24

External Links

•   Clinical Guidelines on treatment HIV-infection in Russia, 2017