Albuminuria Among Virally Suppressed HIV-infected Patients in Botswana: Longitudinal Changes, and Association with Inflammation and ACEI/ARB Use in a Clinical Setting
Living with chronicHIV-infectionis associated with 5-fold risk for albuminuria-abnormal leakage of protein in the urine. People living with HIV (PLWH) who also have albuminuria are up to four times likely to die. While it is well known from non-Africanpopulations that persistent albuminuria and inflammation is a marker of excess end-organ dysfunction and mortality among adults living with HIVdespite attainingundetectable 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 available angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) in reducing albuminuria / inflammation in Africanadultsliving with HIVhas not been studied.
As more PLWHattain 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.
Therefore, the current studypropose 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 enrol 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.
Briefly, the specific objectives of the planned study are:
- Describe the prevalence and longitudinal changes in albuminuria over a 12-month period among treated HIV-infected adults overall, and in relation to use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers.
- Describe the association between albuminuria and inflammation among treated HIV-infected adults overall, and in relation to use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers
- Create a human biorepository and HIV-CVD outcomes clinical registry for the study of long term clinical outcomes of albuminuria
Conducted in collaboration with Botswana-Harvard AIDS Institute Partnership, this project is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP – TMA2017CDF-1928) and is led by Associate Professor Mosepele Mosepele, Department of Internal Medicine, Faculty of Medicine. The project was launched in July 2019, and is expected to last 36 months.