Inflammation and Co-Infections in D²EFT (i2-D²EFT)

Kirby Institute

Status and phase: Withdrawn; Phase 4

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

Treatments: Drug: Ritonavir; Drug: Darunavir; Drug: NRTIs; Drug: Dolutegravir

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT04183738

18Q065 (Other Grant/Funding Number)

2019-10-i2-DEFT

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 3 patient groups

SOC

Active Comparator group

Description:

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

Treatment:

Drug: NRTIs

Drug: Darunavir

Drug: Ritonavir

DOL

Experimental group

Description:

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

Treatment:

Drug: Dolutegravir

Drug: Darunavir

Drug: Ritonavir

D2N

Experimental group

Description:

dolutegravir 50mg + tenofovir + emtricitabine or lamivudine po od

Treatment:

Drug: Dolutegravir

Drug: NRTIs