Inflammation and Co-Infections in D²EFT

NCT04183738 | Withdrawn Phase 4 DMC

• 2 other identifiers: 2019-10-i2-DEFT18Q065
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

i2-D²EFT substudy is an observational cohort nested within the parent D²EFT study (NCT03017872). D²EFT goal is to compare the standard of care second-line antiretroviral therapy in people living with HIV whose first-line non nucleoside reverse transcriptase-based regimen failed, to two simpler regimens. Approximately 1,000 participants will be enrolled in D²EFT. Commencing a second-line ART is an important moment when the level of inflammation in participants may be elevated due to first-line ART failure; this level of inflammation should then decrease with the commencement of a new second-line treatment and would be expected to normalise by 48 weeks of second-line treatment, if successful. The investigators propose to study other factors which can influence the decrease of inflammation. The investigators hypothesise that co-infections may play a role in persistent inflammation. The key-infections of interest will be common frequent infections encounter throughout the world: Human Herpes virus 8, Epstein-Barr virus, Cytomegalovirus and Human papillomavirus, tuberculosis, malaria and other key opportunistic infections. Possible changes of level of inflammation (using the serum level of Interleukin 6) in approximately 200 participants of the D²EFT study will be investigated and measured. The hypothesis is that the presence of other infections than HIV may influence the level of inflammation in participants in therapeutic success.

Conditions

HIV-infection/Aids; Human Herpesvirus 4 Infections; Cytomegalovirus Infections; Human Herpesvirus 8 Infection; Human Papilloma Virus

Keywords

HIV; IL-6; EBV; CMV; HHV8; HPV; inflammation; co-infections; opportunistic infections; AIDS and non-AIDS defining cancers

Outcome Measures

Primary Outcomes (2)

• Change from baseline in IL-6 level at week 48

  To compare the change of a biomarker of inflammation (IL-6) in participants who achieve HIV virological suppression (defined as peripheral blood viral load below 50 copies/mm3 at week 48) across the three study arms according to the presence (or not) of active key-co-infections (HHV8, EBV, CMV, HPV) at baseline and week 48, and the occurrence (or not) within these 48 weeks of any infection (co-infections or opportunistic infections).

  At week 0 and week 48

• Change from baseline of presence/absence of active key co-infections at week 48

  Active key-co-infections (HHV8, EBV, CMV, HPV) at baseline and week 48, and the occurrence (or not) within these 48 weeks of any infection (co-infections or opportunistic infections).

  At week 0 and week 48

Secondary Outcomes (3)

• Prevalence of HHV8, EBV and CMV and of cervical and anal HPV

  At week 0

• Occurrence of active HHV8, EBV and CMV

  At week 48

• Change from baseline in rates of detection of cervical and anal HPV infection at week 48

  At week 0 and week 48

Study Arms (3)

SOC

ACTIVE COMPARATOR

darunavir/ritonavir 800/100mg + 2 NRTIs po od

Drug: NRTIs; Drug: Darunavir; Drug: Ritonavir

DOL

EXPERIMENTAL

darunavir/ritonavir 800/100mg + dolutegravir 50mg po od

Drug: Darunavir; Drug: Ritonavir; Drug: Dolutegravir

D2N

EXPERIMENTAL

dolutegravir 50mg + tenofovir + emtricitabine or lamivudine po od

Drug: NRTIs; Drug: Dolutegravir

Interventions

NRTIs DRUG

In SOC arm, choice of NRTIs determined by clinician, guided by either genotypic resistance testing or use of a protocol-specified algorithm for N(t)RTI selection. In D2N arm, NRTIs are predetermined.

Also known as: Nucleoside/Nucleotide Reverse Transcription Inhibitors

D2N; SOC

Darunavir DRUG

800mg tablet by mouth once daily for 96 weeks.

Also known as: Prezista

DOL; SOC

Ritonavir DRUG

100mg tablet by mouth once daily for 96 weeks.

Also known as: Norvir

DOL; SOC

Dolutegravir DRUG

50mg tablet by mouth once daily for 96 weeks.

Also known as: Tivicay

D2N; DOL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fulfil the eligibility criteria for D²EFT randomisation;
• Being able to give a written informed consent for the i2-D²EFT sub-study.

You may not qualify if:

• Unwilling to comply with the i2-D²EFT protocol requirements.

Sponsors & Collaborators

• Kirby Institute: lead
• Frederick National Laboratory for Cancer Research: collaborator
• UNITAID: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• ViiV Healthcare: collaborator
• Janssen Pharmaceutica: collaborator

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Epstein-Barr Virus Infections; Cytomegalovirus Infections; Inflammation; Coinfection; Opportunistic Infections

Interventions

Nucleosides; Darunavir; Ritonavir; dolutegravir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Tumor Virus Infections; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycosides; Carbohydrates; Nucleic Acids, Nucleotides, and Nucleosides; Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles

Study Officials

• Mark Polizzotto, MD, PhD

  Kirby Institute, UNSW Sydney, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Observational cohort nested within the parent open label phase III/IV randomised controlled trial of simplified second-line therapy, D²EFT.

Study Record Dates

• First Submitted: November 28, 2019
• First Posted: December 3, 2019
• Study Start: February 1, 2021
• Primary Completion: December 19, 2022
• Study Completion: December 19, 2022
• Last Updated: November 10, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share