"Observational Study on Tolerability and Observance of Post-exposure Prophylaxis With Doravirine in HIV Viral Risk"

HIV Infections Clinical Trial

— DORASPEP  

Official title:

"Observational Study on Tolerability and Observance of Post-exposure Prophylaxis With Doravirine in HIV Viral Risk"

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05761509
• Other study ID #: IMEA 067
• Secondary ID: N° IDRCB: 2022-A
• Status: Active, not recruiting
• Start date: June 8, 2023
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2024
• Source: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The main objective of this observational study is to assess the adherence of post exposure prophylaxis treatment with doravirine (using Delstrigo® or Pifeltro®), prescribed to subjects exposed to HIV according to French national recommendations. This study will evaluate: - the percentage of subjects who followed their treatment within the prescribed 28 days, - the prevalence and type of side effects in subjects on this treatment, - the occurrence of HIV seroconversion associated with this combination.

Description:

The study visits are those routinely performed in the standard care of the subjects using PEP and are the following: Visit 1 (between day 1 to day 8 after PEP treatment initiation): - Subject information and inclusion in the study, - Pregnancy test (urine or serum) for women of childbearing potential (WOCBP) - Delivery of a follow-up subject diary (daily information about PEP treatment intake, concomitant treatments and potential side effects/adverse events) Visit 2 (From 42 days to 90 days after PEP treatment initiation) - Treatment observance (PEP), - Return of the follow-up subject diary, - Check of the follow-up subject diary completion, - Keep a copy of the HIV serology and/or viral load results in the medical file.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 226
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age more than 18 years old

2. Exposure to HIV, leading to the prescription of 28-day post exposure prophylaxis (PEP)

3. PEP with doravirine:

1. Delstrigo® (tenofovir disoproxil, doravirine, lamivudine),

2. Or Pifeltro® (doravirine) in association with tenofovir disoproxil/emtricitabine.

4. Participant who can understand, read and speak French.

5. With or without health insurance.

6. Cisgender female and Female to Male transgender participants are eligible to participate if they are not pregnant or breastfeeding, and at least one of the following conditions applies: •

1. Is not a WOCBP (Women Of Childbearing Potential) OR

2. Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the treatment period and for at least 8 weeks after the last dose. The investigator should evaluate the potential for contraceptive method failure (i.e., non compliance, recently initiated) in relationship to the first dose of PEP treatment. A WOCBP must have a negative pregnancy test (urine or serum) before inclusion in the study. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant should not be included in the study if the serum pregnancy result is positive.

Exclusion Criteria:

1. Contraindication to Delstrigo® or Pifeltro® or tenofovir disoproxil/emtricitabine:

hypersensitivity to active substances or excipients.

2. Contra-indicated treatment likely to interfere with the study drugs as listed in the summary of the product characteristics.

3. Viral resistance of the source subject known and unsuitable for the prescription of doravirine

4. Simultaneous participation in another clinical trial with an experimental treatment or any intervention, which may have impact/change onto the PEP treatments or within an exclusion period of a previous clinical trial at screening.

5. Subjects under legal guardianship or unable to express their consent.

6. Subject privated of liberty by judicial or administrative decision or subject under psychiatric care or admitted to a health or social establishment.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Doravirine
The study treatments will used during 28 days according to the routine care of each investigator center.

Locations

Country	Name	City	State
France	Service de maladies infectieuses et tropicales du CHU de Montpellier	Montpellier
France	Hopital Saint Antoine	Paris
France	Service de maladies infectieuses et tropicales de de l'hôpital La Pitié-Salpêtrière	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

France, 

References & Publications (13)

Asante-Appiah E, Lai J, Wan H, Yang D, Martin EA, Sklar P, Hazuda D, Petropoulos CJ, Walworth C, Grobler JA. Impact of HIV-1 Resistance-Associated Mutations on Susceptibility to Doravirine: Analysis of Real-World Clinical Isolates. Antimicrob Agents Chemother. 2021 Nov 17;65(12):e0121621. doi: 10.1128/AAC.01216-21. Epub 2021 Sep 27. — View Citation

Assoumou L, Bocket L, Pallier C, Grude M, Ait-Namane R, Izopet J, Raymond S, Charpentier C, Visseaux B, Wirden M, Trabaud MA, Le Guillou-Guillemette H, Allaoui C, Henquell C, Krivine A, Dos Santos G, Delamare C, Bouvier-Alias M, Montes B, Ferre V, De Monte A, Signori-Schmuck A, Maillard A, Morand-Joubert L, Tumiotto C, Fafi-Kremer S, Amiel C, Barin F, Marque-Juillet S, Courdavault L, Vallet S, Beby-Defaux A, de Rougemont A, Fenaux H, Avettand-Fenoel V, Allardet-Servent A, Plantier JC, Peytavin G, Calvez V, Chaix ML, Descamps D; ANRS AC-43 Resistance Study Group. Stable prevalence of transmitted drug resistance mutations and increased circulation of non-B subtypes in antiretroviral-naive chronically HIV-infected patients in 2015/2016 in France. J Antimicrob Chemother. 2019 May 1;74(5):1417-1424. doi: 10.1093/jac/dkz011. — View Citation

Delstrigo: Product information from the European Medecines Agency: https://www.ema.europa.eu/en/medicines/human/EPAR/delstrigo#product-information-section

Eviplera: Product information from the European Medecines Agency: https://www.ema.europa.eu/en/medicines/human/EPAR/eviplera

Gantner P, Hessamfar M, Souala MF, Valin N, Simon A, Ajana F, Bouvet E, Rouveix E, Cotte L, Bani-Sadr F, Hustache-Mathieu L, Lebrette MG, Truchetet F, Galempoix JM, Piroth L, Pellissier G, Muret P, Rey D; E/C/F/TAF PEP Study Group. Elvitegravir-Cobicistat-Emtricitabine-Tenofovir Alafenamide Single-tablet Regimen for Human Immunodeficiency Virus Postexposure Prophylaxis. Clin Infect Dis. 2020 Feb 14;70(5):943-946. doi: 10.1093/cid/ciz577. — View Citation

Genvoya: Product information from the European Medecines Agency: https://www.ema.europa.eu/en/medicines/human/EPAR/genvoya

HIV drugs interactions, University of Liverpool: http://www.hiv-druginteractions.org

Inciarte A, Leal L, Gonzalez E, Leon A, Lucero C, Mallolas J, Torres B, Laguno M, Rojas J, Martinez-Rebollar M, Gonzalez-Cordon A, Cruceta A, Arnaiz JA, Gatell JM, Garcia F; STRIBPEP Study Group. Tenofovir disoproxil fumarate/emtricitabine plus ritonavir-boosted lopinavir or cobicistat-boosted elvitegravir as a single-tablet regimen for HIV post-exposure prophylaxis. J Antimicrob Chemother. 2017 Oct 1;72(10):2857-2861. doi: 10.1093/jac/dkx246. — View Citation

Pham HT, Xiao MA, Principe MA, Wong A, Mesplede T. Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Drugs Context. 2020 Mar 3;9:2019-11-4. doi: 10.7573/dic.2019-11-4. eCollection 2020. — View Citation

Pifeltro: Product information from the European Medecines Agency: https://www.ema.europa.eu/en/medicines/human/EPAR/pifeltro

Rapport Morlat : Prise en charge des accidents d'exposition sexuelle et au sang (AES) chez l'adulte et l'enfant (septembre 2017) https://cns.sante.fr/wp-content/uploads/2017/10/experts-vih_aes.pdf.

Scheibe K, Urbanska A, Jakubowski P, Hlebowicz M, Bociaga-Jasik M, Raczynska A, Szymczak A, Szetela B, Lojewski W, Parczewski M. Low prevalence of doravirine-associated resistance mutations among polish human immunodeficiency-1 (HIV-1)-infected patients. Antivir Ther. 2021 May;26(3-5):69-78. doi: 10.1177/13596535211043044. Epub 2021 Oct 20. — View Citation

Valin N, Fonquernie L, Daguenel A, Campa P, Anthony T, Guiguet M, Girard PM, Meyohas MC. Evaluation of tolerability with the co-formulation elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate for post-HIV exposure prophylaxis. BMC Infect Dis. 2016 Nov 29;16(1):718. doi: 10.1186/s12879-016-2056-3. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the adherence of post exposure prophylaxis treatment with doravirine (using Delstrigo® or Pifeltro®), prescribed to subjects exposed to HIV according to French national recommendations.	Proportion of subjects who complete the total period of treatment (intake during 28 days).; The treatment completeness will be defined as follows: no missing treatment intake from D1 to D14,; and no more than 2 missing treatment intakes from D15 to D28.	3 months
Secondary	To evaluate the tolerability of PEP with doravirine.	Number and type of side effects.	28 days
Secondary	To evaluate the prevalence of HIV seroconversion associated with this combination.	Number of subjects with seroconversion.	3 months
Secondary	To compare the adherence of post exposure prophylaxis treatment between Delstrigo® or Pifeltro®	Proportion of subjects who complete the total period of each treatment (intake during 28 days).	28 days

External Links

•   Delstrigo: Product information from the European Medecines Agency
•   Eviplera: Product information from the European Medecines Agency
•   Genvoya: Product information from the European Medecines Agency
•   HIV drugs interactions, University of Liverpool
•   Pifeltro: Product information from the European Medecines Agency
•   Rapport Morlat : Prise en charge des accidents d'exposition sexuelle et au sang (AES) chez l'adulte et l'enfant (septembre 2017)