Trials / Completed

CompletedNCT04340388

Contribution of Dolutegravir to Obesity and Cardiovascular Disease

Contribution of the Integrase Inhibitor Dolutegravir to Obesity and Cardiovascular Disease in Persons Living With HIV

Status: Completed
Phase: Phase 4
Study type: Interventional
Enrollment: 10 (actual)

Sponsor: Augusta University · Academic / Other
Sex: All
Age: 18 Years – 100 Years
Healthy volunteers: Not accepted

Summary

The goal of the study is to combine a collaborative and translational approach to evaluate the effect antiretroviral regimen switch to a dolutegravir containing regimen compared to continued treatment with a non- dolutegravir based regimen on on lipid and metabolic profiles, renal function, body composition, vascular function and diet.

Detailed description

Over the last decades, the use of combined antiretroviral therapy has led to profound suppression of HIV-1 replication and increased the survival of persons living with HIV (PLWH) to close to that of the general population. As a consequence, the spectrum of diseases related to HIV has shifted from opportunistic AIDS-related diseases towards long-term-age-related complications. Individuals living with HIV are now exhibiting accelerated development of obesity, metabolic derangements and cardiovascular disease (CVD). Recent compelling clinical evidence has documented a drastic shift in anthropometric profiles among persons living with HIV. In addition, several reports present dolutegravir, a second-generation integrase inhibitor currently highly prescribed for its high antiviral efficiency, as the potential cause of unpredicted weight gain. A critical gap in the investigators' knowledge is a lack of understanding of the etiopathology of the contribution of dolutegravir on weight gain and the consequential impact on obesity and cardiovascular disease in persons living with HIV on combined antiretroviral therapy. As overweight and obesity are among the leading risk factors for cardiovascular disease in persons living with HIV, it is critical to directly investigate whether dolutegravir increases fat mass in persons living with HIV and whether body weight gains-associated with dolutegravir based regimen contribute to the increased prevalence of CVD in this population of people. This application seeks to investigate alterations in body fat and cardiometabolic risk markers associated with dolutegravir. The investigators propose that in patients with undetectable plasma HIV RNA, there is a direct correlation of weight gain and dolutegravir after antiretroviral regimen switch. They also contend that dolutegravir associated weight gain induces a phenotypic metabolic shift which alters the vascular endothelium and potentiates CVD risk. If the investigators are correct in their hypotheses, modifications in the clinical practice of treatment and prevention strategies for CVD in people living with HIV may be warranted. Herein the investigators propose a novel translational study which will concomitantly investigate in human patients and animal models of HIV: 1. whether dolutegravir based regimen increases body weight 2. the mechanisms whereby dolutegravir increases body weight 3. whether dolutegravir-mediated body weight gain increases the risk for CVD in PLWH.

Conditions

Interventions

Type	Name	Description
DRUG	Dolutegravir 50 MG	15 participants will be randomized to remain on fully suppressive background antiretroviral therapy. The third agent will be switched to dolutegravir at the dose of 50 mg daily.
DRUG	Antiretroviral/Anti HIV	15 participants with suppressed HIV disease for greater than or equal to 3 months will be randomized to remain on their current 2 or 3 drug fully suppressive antiretroviral regimen.

Timeline

Start date: 2020-09-17
Primary completion: 2022-06-17
Completion: 2023-02-25
First posted: 2020-04-09
Last updated: 2023-07-27

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT04340388. Inclusion in this directory is not an endorsement.