Non-Interventional Observational Retrospective Study to Evaluate Doravirine Based-regimens in HIV Infected Aged Patients (DORAge). (DORAge)

The HIV-infected population is aging due to the success of combination antiretroviral therapy, which prolongs survival, as well as the growing number of newly diagnosed cases in adults 50 years old and over. This real-life, observational and retrospective study aims to evaluate the virological efficacy, toxicity and tolerability of Doravirine-based regimens in aged HIV-1 positive patients (> 50 years), focusing on metabolic patterns and inflammation markers.

Study Overview

• Status: Recruiting
• Conditions: HIV
• Intervention / Treatment: Drug: Doravirine

Detailed Description

HIV-infected individuals suffer from an accelerated aging due to the persistent and chronic activation of the immune system that leads to immune exhaustion and accelerated immunosenescence. The success of combination antiretroviral therapy, which also prolongs patients' survival, have relatively higher retention rates among HIV infected elderly patients, but only a small percentage are virally suppressed, largely due to elderly drugs interacts with ART and several comorbidities that reduces the life span of elderly people.

In this context, Doravirine is the only NNRTI with a low propensity for resistance, excellent tolerability, a superior neuropsychiatric profile compared with EFV, a superior lipid profile compared with ritonavir-boosted darunavir and EFV, minimal risk for drug- drug interactions, and no food restrictions. In addition, doravirine has a large therapeutic index and robust efficacy in patients with high viral load. However, to date, data on doravirine in HIV aged patients are still lacking.

This observational retrospective cohort in real world will aim to describe the effect of doravirine regimens, both as single drug and as fixed combination with lamivudine and tenofovir disoproxil fumarate, in aged HIV patients.

• The primary endpoint will be the evaluation of virological efficacy defined as the proportion of patients with HIV RNA < 50 copies/mL at the end of the 48-week follow-up.

• The secondary endpoints will be the following:

  • Change in CD4+, CD8 cell counts, CD4/ CD8 ratio from baseline to 48 weeks
  • Proportion of patients with any adverse events (AE), serious adverse events (SAE), also according to their severity.
  • Changes in total HDL and LDL-cholesterol, triglycerides, creatinine, eGFR, phosphate, AST, ALT, FIB-4, ALP, glucose, proteinuria from baseline to 48 weeks.
  • Changes of infiammatory biomarkers: D-Dimer, hsCRP and IL-6 during 48 weeks
  • Occurrence of genotypic mutations (genotypic test) in plasma samples from patients with virological failure

Clinical data will be collected from medical records and laboratory analyses comprising CD4+ T cell count, plasma HIV-1 RNA, blood cells, and plasma chemistry profiles, including fasting lipids (total cholesterol, high-density lipoprotein cholesterol [HDL], low- density lipoprotein [LDL] cholesterol, triglycerides) will be recorded.

The Time horizon for patient follow-up for outcome is at least 12 months (Baseline, 12, 24, 36, 48 weeks).

• Study Type: Observational
• Enrollment (Anticipated): 90

Contacts and Locations

• Study Contact: Name: Gabriella d'Ettorre, Professor, MD; Phone Number: 0649970801; Email: gabriella.dettorre@uniroma1.it

Study Locations

• Italy
  • Italy/RM
    • Rome, Italy/RM, Italy, 00185
      • Recruiting
      • Department of Public Health and Infectious Diseases
      • Contact: Gabriella d'Ettorre, Professor, MD; Phone Number: 0649970801; Email: gabriella.dettorre@uniroma1.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV infected patients

Description

Inclusion Criteria:

• HIV-1 infected patients
• aged > 50 years old
• naive patients receiving doravirine-based regimens both as single drug and as in fixed combination with lamivudine and tenofovir disoproxil fumarate
• experienced patients with persistently undetectable plasma HIV viral load (HIV RNA < 50 copies/mL) for at least 6 months, who switched from any antiretroviral drug to doravirine-based regimens, both as single drug and as fixed combination with lamivudine and tenofovir disoproxil fumarate, because of toxicity, convenience or other reasons.
• estimated creatinine clearance (CrCl) ≥50mL/min.

Exclusion Criteria:

• previous genotypic testing showing resistance mutations to doravirine
• acute hepatitis, decompensated liver disease, liver cirrhosis
• use of systemic immunosuppressive therapy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Dorage group; HIV-1 infected patients; aged > 50 years old; naive patients receiving doravirine-based regimens; experienced patients with persistent HIV RNA < 50 copies/mLfor at least 6 months, who switched to doravirine-based regimens, because of toxicity, convenience or other reasons.	Drug: Doravirine; Doravirine, both as single drug and as fixed combination with lamivudine and tenofovir disoproxil fumarate
Control group; HIV negative subjects, matched for age and Charlson Index score (to evaluate comorbidity impact)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological efficacy	Assessing the virological efficacy (HIV RNA < 50 copies/mL) of the Doravirine regimen at the end of the follow-up.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to virological failure		48 weeks
Immunological changes	Change in CD4+, CD8 cell counts, CD4/ CD8 ratio	Baseline to 48 weeks
Safety profile	Proportion of patients with any adverse events (AE), serious adverse events (SAE), also according to their severity.	Baseline to 48 weeks
Lipid and metabolic profile	Changes in total HDL and LDL-cholesterol, triglycerides, creatinine, eGFR, phosphate, AST, ALT, FIB-4, ALP, glucose, proteinuria	Baseline to 48 weeks
Infiammatory biomarkers	Evaluation of D-Dimer, hsCRP and IL-6	48 weeks
Resistance profile in patients with virological rebound	Evaluation of of genotypic mutations occurrence (genotypic test) in plasma samples from patients with virological failure	Baseline to 48 weeks

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 4, 2022
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: January 11, 2022
• First Submitted That Met QC Criteria: January 11, 2022
• First Posted (ACTUAL): January 21, 2022

Study Record Updates

• Last Update Posted (ACTUAL): January 21, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Inflammation; HIV; Metabolism; Doravirine; Virological Failure
• Other Study ID Numbers: 6496

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No