Variation in Drug Interactions in People With HIV (PLWH) Aged 60 Years and Older.

Recruiting

• Conditions: HIV Infections; Drug Interaction; Elderly Infection; Comorbidities and Coexisting Conditions; Cardiovascular Diseases; Metabolic Disease; Renal Disease; Osteoporosis Risk; Neoplasms

• Registration Number: NCT06717581
• Lead Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Brief Summary

Several cohort studies have recently shown a significant increase in the mean age of PLWH ( People Living With HIV) and in the prevalence of people in advanced age in the various cohorts, as a result of the marked increase in the mean life expectancy of these people achieved by modern antiretroviral combination therapies.

However, the high prevalence of comorbidities exposes PLWH in old age to the need to take multiple drug treatments in addition to antiretroviral therapy, with the gradually increasing risk of unfavorable pharmacokinetic interactions between antiretroviral drugs and drugs taken to treat the comorbidities.

This project consists of an observational, cohort, retrospective, single-center study and aims to evaluate the variation in the number and type of clinically significant drug interactions between antiretroviral therapy and concomitant therapies in PLWH aged \>60 years on stable antiretroviral therapy who, for any reason at the Clinician's discretion, have made a switch from ongoing antiretroviral therapy to the bictegravir/emtricitabine/tenofovir alafenamide regimen.

Detailed Description

The introduction of integrase inhibitors into clinical practice has greatly improved the efficacy and tolerability of modern antiretroviral combination therapies for the treatment of patients with HIV-1 infection. Indeed, these drugs have shown in registration studies high antiviral potency associated with a negligible incidence of short- and long-term adverse events, so much so that they are consistently included in the drug regimens recommended by all international guidelines for the treatment of HIV-positive patients naive to antiretroviral therapy.

Several cohort studies have recently shown a significant increase in the mean age of PLWH ( People Living With HIV) and in the prevalence of people in advanced age in the various cohorts, as a result of the marked increase in the mean life expectancy of these people achieved by modern antiretroviral combination therapies.

PLWH in advanced age, however, have a high prevalence of noninfectious comorbidities (cardiovascular disease, metabolic abnormalities, chronic renal failure, osteopenia-osteoporosis, neoplastic diseases, etc.), brought about by age-related aging but also by their accelerated biological aging caused by HIV infection and associated chronic inflammation and immunoactivation.

The high prevalence of comorbidities exposes PLWH in old age to the need to take multiple drug treatments in addition to antiretroviral therapy, with the gradually increasing risk of unfavorable pharmacokinetic interactions between antiretroviral drugs and drugs taken to treat the comorbidities.

The effect of such interactions can be either a reduction in plasma concentrations with reduced efficacy of antiretroviral drugs or an increase in plasma levels of concomitant drugs and the risk of toxicity induced by them.

The availability of integrase inbitors such as bictegravir, i.e., antiretroviral drugs characterized by a very low risk of drug interactions (because they are generally not metabolized by hepatic cytochrome P450 3A4 isoenzymes), has made it possible to significantly reduce the risk of interactions between antiretroviral therapy and concomitant therapy, especially in people of advanced age, while providing high viro-immunologic efficacy and a favorable effect on the cardio-metabolic profile.

This project consists of an observational, cohort, retrospective, single-center study and aims to evaluate the variation in the number and type of clinically significant drug interactions between antiretroviral therapy and concomitant therapies in PLWH aged \>60 years on stable antiretroviral therapy who, for any reason at the Clinician's discretion, have made a switch from ongoing antiretroviral therapy to the bictegravir/emtricitabine/tenofovir alafenamide regimen.

Study Timeline

• Study Start: 2024-10-11
• Status Verified: 2024-12
• Study First Submitted: 2024-12-01
• Study First Submitted QC: 2024-12-01
• Last Update Submitted: 2024-12-01
• Study First Posted: 2024-12-05
• Last Update Posted: 2024-12-05
• Primary Completion: 2025-04-11
• Study Completion: 2025-10-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Age > 60 years
• Non-infectious comorbidities receiving drug therapy
• Receiving BIC/TAF/FTC therapy at the time of of enrollment

Exclusion Criteria

• Genotypic resistance testing that present or past evidence of viral resistance to the integrase inhibitor class, to emtricitabine or to tenofovir
• Severe acute infectious disease

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Evaluation of the change in the total number of clinically significant drug-drug interactions (DDIs)	12 Months	Evaluation of the change in the total number of clinically significant drug-drug interactions (DDIs) between antiretroviral drugs and concomitant drugs following therapeutic switch to bictegravir/emtricitabine/tenofovir alafenamide.
Evaluation of the change in the number of clinically significant DDIs between antiretroviral drugs and drugs of specific therapeutic classes	12 Months	Evaluation of the change in the number of clinically significant DDIs between antiretroviral drugs and drugs of specific therapeutic classes (cardiovascular, hypolipidemic, hypoglycemic, neurological/psychiatric, etc.) following therapeutic switch to bictegravir/emtricitabine/tenofovir alafenamide

Secondary Outcome Measures

Name	Time	Method
Evaluation of viro-immunological parameters and incidence of clinical adverse events and treatment discontinuations	12 Months	Evaluation of viro-immunological parameters and incidence of clinical adverse events and treatment discontinuations during the follow-up period.

Trial Locations

Locations (1)

IRCCS Azienda Ospedaliero-Universitaria di Bologna; 🇮🇹 Bologna, Italy