Project: Albuminuria Among Virally Suppressed HIV-infected Patients in Botswana: Longitudinal Changes, and Association with Inflammation and ACEI/ARB Use in a Clinical Setting

Acronym	Albuminuria and ACEI/ARB among HIV-patients (Reference Number: TMA2017CDF-1928)
Duration	01/07/2019 - 30/06/2022
Project Topic	Having HIV is associated with 5-fold risk for albuminuria. Albuminuria among HIV-infected patients are up to four times likely to die. While it is well known from Western populations that persistent albuminuria and inflammation is a marker of excess end-organ dysfunction and mortality among HIV-infected adults with undetectable HIV-1 RNA (viral load suppression on antiretroviral treatment or ART), the burden of albuminuria / inflammation has not been well characterized among black African patients. In addition, the role of widely globally available angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) in reducing albuminuria / inflammation in African HIV-infected patients has not been studied. As more HIV-infected patients attain viral suppression and prolonged survival globally (particularly with the rollout of universal ART), they are faced with multiple non-communicable diseases mostly characterized by accelerated end-organ dysfunction which threatens their long-term health and longevity. It is believed that persistent inflammation despite viral suppression drives most of the observed end-organ dysfunction. Studies involving HIV-infected and HIV-uninfected persons outside of Africa have shown albuminuria to be a marker of end-organ dysfunction (e.g. cardiovascular disease, renal dysfunction, and even cognitive impairment), and demonstrate that albuminuria is highly correlated with inflammation. We therefore propose to determine prevalence and longitudinal changes in albuminuria in a clinical setting with high rates of viral suppression. We will also assess if longitudinal changes in albuminuria is associated with ACEI/ARB exposure over a 12-month period in a clinical setting. Second, we will assess the association between longitudinal changes in albuminuria and inflammatory markers and whether this association is affected by use of ACEI/ARB. Finally, we plan to enroll a cohort for long-term HIV-CVD outcomes with storage of bio specimens for future testing of other inflammatory markers plus host genetics (e.g., APOL-1 allele variant frequency) and assess 5-year mortality in the dearth registry linked to longitudinal changes in albuminuria. Research experience gained by conducting this prospective non-interventional study will provide the applicant with skills to assess impact of drug therapies on clinical outcomes (health benefits). In addition, results of this observational study will provide baseline data to inform the design of a trial to assess whether HIV disease in a compelling indication for early ACEI/ARB prescription among hypertensive HIV-infected patients given the positive pleotropic effects of these medications on albuminuria, inflammation and cardiac remodeling. The applicant would plan to lead such a trial in the future.
Network	EDCTP2
Call	Career Development Fellowships 2017

Project partner

Number	Name	Role	Country
1	University of Botswana	Coordinator	Botswana