Clinical trial NCT04183738: Inflammation and Co-Infections in D²EFT
Official title: The Impact of Co-infections on Inflammation in Patients Commencing Second-line Antiretroviral Therapy. A Sub-study of D²EFT (Dolutegravir and Darunavir Evaluation in Adults Failing Therapy)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
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
Lead sponsor: Kirby Institute
Sponsor class: OTHER_GOV
Collaborators: name: Frederick National Laboratory for Cancer Research
name: UNITAID
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: ViiV Healthcare
name: Janssen Pharmaceutica
First posted: 2019-12-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Observational cohort nested within the parent open label phase III/IV randomised controlled trial of simplified second-line therapy, D²EFT.
Primary purpose: BASIC_SCIENCE

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.

Detailed description: i2-D²EFT substudy an observational cohort nested within the parent open label phase III/IV randomised controlled trial of simplified second-line therapy, D²EFT (NCT03017872). Participants consenting to D²EFT study will be randomised within the three arms: either ritonavir-boosted darunavir plus two nucleosides or dolutegravir plus two predetermined nucleosides (tenofovir disoproxil fumarate plus lamivudine or emtricitabine) or ritonavir-boosted darunavir plus dolutegravir. Enrolment into the i2-D²EFT substudy is voluntary and optional for participants in D²EFT. Parameters relevant to i2-D²EFT substudy including demographics, arm of randomised ART, HIV history, physical examination, immunological and virological results, episodes of co-infections and adverse events due to any infection or malignancies at required time points will be collected as part of D²EFT study. Substudy specific assessments performed at baseline and at weeks 48 include sample collection for IL-6 dosage plus EBV/CMV/HHV8 testing, and optional anal/cervical HPV screening.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Change from baseline in IL-6 level at week 48
timeFrame: At week 0 and week 48
measure: Change from baseline of presence/absence of active key co-infections at week 48
timeFrame: At week 0 and week 48
Secondary outcomes:
measure: Prevalence of HHV8, EBV and CMV and of cervical and anal HPV
timeFrame: At week 0
measure: Occurrence of active HHV8, EBV and CMV
timeFrame: At week 48
measure: Change from baseline in rates of detection of cervical and anal HPV infection at week 48
timeFrame: At week 0 and week 48
Other outcomes:
Locations:
Study officials:
affiliation: Kirby Institute, UNSW Sydney, Australia
name: Mark Polizzotto, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: