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Impact of V106I on Resistance to Doravirine

NCT04894357 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 50

Last updated 2021-08-18

No results posted yet for this study

Summary

Objective. To study the impact of V106I mutation in the reverse transcriptase of HIV-1 on the activity of Doravirine.

Clinical hypotheses.

Doravirine shows a unique resistance pattern with a higher genetic barrier to resistance than other NNRTIs. In contrast to K103N or E138A, the prevalence of single mutations and/or combination of mutations against Doravirine is low. However, in a recent survey conducted in Spain the study investigators have found a V106Iprevalence similar to K103N and E138A. There is a clear need to understand the real impact of this mutation on Doravirine resistance.

Conditions

Interventions

OTHER

Phenotypic resistance measure

SDM experiments: Reverse transcriptase mutants of HIV-1 will be obtained by site-directed mutagenesis using specific primers introducing the expected mutations into plasmids pNL4.3 and CRF02\_AG. HIV-1 stocks will be obtained by transfecting 293-T cells with the various HIV-1 molecular clones. 48 hours after transfection, the viral supernatants will be recovered, quantified for HIV-1p24gag antigen (Vidas BioMérieux) and frozen at -80°C.The single-cycle virus titers will be determined on HeLa-P4 cells in which the expression of b-galactosidase is inducible by the HIV Tat protein. Phenotypic analysis: creation of replication competent chimeric viruses through homologous recombination between patient or laboratory virus-derived PCR fragments and the corresponding NL4-3 vector where the whole Gag-PR, RT-RNaseH or IN coding regions have been deleted through inverse PCR. The susceptibility to Doravirine will be calculated through a single round infection assay in TZM-bl cells.

Sponsors & Collaborators

  • Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental

    lead OTHER

Eligibility

Min Age
13 Years
Max Age
75 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2021-09-01
Primary Completion
2021-10-01
Completion
2022-05-01

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04894357 on ClinicalTrials.gov