Protective Effect of Angiotensin-Converting Enzyme Inhibitor Therapy Among Persons With HIV and Proteinuria

Abstract

To the Editors: Proteinuria has been shown to be predictive of death in populations with and without HIV disease.1,2 In addition to diagnosing HIV infection early to prompt timely initiation of antiretroviral therapy, early consideration of angiotensin-converting enzyme (ACE) inhibitor therapy among persons with HIV and proteinuria to improve survival should be considered. To determine the potential protective effect of ACE inhibitor therapy for selected adverse outcomes among patients with HIV and proteinuria, a retrospective review of a large ambulatory clinic population with HIV based in New Orleans was performed. Patients were eligible for the study if they were ≥18 years and had at least 2 valid urinalyses between 7/06 and 6/08. Urinalyses showing gross blood (defined as ≥10 red blood cells per high-power field) and/or pyuria (defined as ≥10 white blood cells per high-power field) were considered invalid. Patients meeting the study criteria were followed up through 6/11 for hospitalization and all-cause mortality. Of the 140 patients having at least 2 valid urinalyses, 41 (29%) had ≥2 tests, 43 (31%) had only 1 test, and 56 (40%) had no urinalyses demonstrating proteinuria at levels of ≥25 mg/dL. Characteristics of the cohort showed 38 (27%) were women and 109 (78%) were African American. Median baseline age, CD4 cell count, and HIV RNA copies were 45 years, 154 cells per cubic millimeter, and 63,900 copies per milliliter, respectively. Of the 140 patients, 39 (28%) were on an ACE inhibitor. Bivariate analysis showed that ever proteinuria was not associated with sex, race, age, substance use, antiretroviral therapy, body mass index, systolic or diastolic blood pressure, ACE therapy, or selected medical conditions (including diabetes, hypertension, renal disease, and hepatitis). Proteinuria (levels ≥25 mg/dL on ≥1 urinalysis) was associated with ever having a CD4 cell count <200 cells per cubic millimeter (P = 0.03), a detectable HIV RNA level >400 copies per milliliter (P = 0.03), or a baseline albumin level of <3.5 mg/dL. On bivariate analyses, proteinuria was also significantly associated with hospitalization or death, but only in patients not on an ACE inhibitor. As shown in Table 1, on multivariate analyses including the entire cohort, the association between proteinuria and hospitalization or death remained significant after controlling for confounding factors (including sex, race, CD4 count, HIV RNA level, creatinine, and baseline albumin). In analyses stratified by ACE inhibitor therapy, the association between the adverse outcomes and proteinuria was only significant among patients not on an ACE inhibitor. Patients off an ACE inhibitor compared with those on an ACE inhibitor had 2 and 4 times the risk of hospitalization and death, respectively.TABLE 1: Proteinuria* as a Risk of Hospitalization and Death Stratified by ACE Inhibitor TherapyOur results demonstrate that both recurrent and ever low-level proteinuria were relatively common among persons with advanced HIV disease. Hospitalization and death outcomes were more frequent among all persons with ever compared with never proteinuria. However, proteinuria was a significant predictor for these adverse outcomes only among persons not on an ACE inhibitor. Our data suggest that patients with HIV and any proteinuria, even episodic low levels, may benefit from ACE inhibitor therapy. Larger prospective studies need to confirm these results.