Background: There is increasing evidence of hypertension and microalbuminuria in HIV-infected patients, and these are two important risk factors for renal and cardiovascular disease. Anti-hypertensive drugs inhibiting the renin-angiotensin system exert an antiproteinuric effect. Telmisartan, an angiotensin II receptor blocker and partial peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist that is approved for the treatment of hypertension, appears to exert a nephroprotective effect independent of blood pressure reduction in the general population.
Objective: The aim of this preliminary study was to evaluate possible nephroprotective effects of telmisartan in hypertensive HIV-positive patients with microalbuminuria.
Patients and methods: Caucasian male patients with HIV infection (n=13) receiving stable combined antiretroviral therapy (without therapeutic changes for > 12 months) and a recent diagnosis of grade 1 hypertension were treated with daily oral telmisartan 80 mg for 6 months. Patients had suppressed viremia and a CD4 cell count > 300 cells/mL for 6 months, and microalbuminuria > 5 mg/dL. Systolic and diastolic blood pressure (SBP, DBP), triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), microalbuminuria, Modification of Diet Renal Disease-Glomerular Filtration Rate (MDRD-GFR), vascular endothelial growth factor (VEGF) and endothelin-1 were measured at baseline and at one, three and six months. All statistical analyses were performed using SAS 9.2.
Results: A significant reduction of microalbuminuria (p < 0.001) with stable MDRD-GFR was observed, although the main indices of renal function showed no substantial change. A significant reduction in mean SBP and DBP was observed at T1 and confirmed at T3 and T6 (SBP p < 0.001 and DBP p < 0.001), and there was BP normalization. Metabolic assessments showed an improvement in lipid parameters, and a significant decrease in insulin resistance assessed by the homeostasis model assessment index-insulin resistance (HOMA-IR) (p = 0.04). In addition, there was a statistically significant reduction in ESR (p = 0.02) and a non significant reduction in CRP. Other results included a significant reduction in serum VEGF and endothelin-1 levels (p < 0.001).
Conclusions: From these preliminary findings, telmisartan has demonstrated efficacy in the control of hypertension and microalbuminuria in HIV-infected patients. Decreased microalbuminuria with stable MDRD-GFR may be indicative of a nephroprotective effect of telmisartan; mechanisms causing microalbuminuria in patients with HIV could be related to infection, chronic inflammation, and endothelial dysfunction. The decreased endothelin-1 and VEGF levels in patients in this study may be related to an endothelial protective effect of telmisartan. This study reports the first observation of renal and endothelial protective effects of telmisartan in HIV-positive patients.