The effects of highly active antiretroviral therapy on albuminuria in HIV-infected persons: results from a randomized trial.
BACKGROUND
Human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) regimens, especially those containing protease inhibitors (PIs), are at increased risk for cardiovascular events. Albuminuria is a known independent predictor for the development of cardiovascular disease and may potentially increase in patients receiving PIs. Alternatively, albuminuria may improve with HAART as a result of treating renal parenchymal HIV infection. Longitudinal studies have not been performed previously addressing the effects of HAART on albuminuria.


METHODS
We evaluated the effects of HAART on albumin to creatinine ratios (ACRs) during the initial 64 weeks of therapy in 68 previously untreated HIV-infected subjects, without pre-existing diagnosed diabetes or hypertension, enrolled in a randomized trial comparing PI-based (n = 32) with non-PI-based (n = 36) HAART regimens. We also estimated the prevalence of albuminuria, defined as an ACR > or =3.4 mg/mmol, in these subjects prior to initiation of HAART.


RESULTS
The changes in ACR over the initial 64 weeks of therapy in those receiving PIs [0.0 mg/mmol (-0.4, 0.3)] and in those not receiving PIs [0.0 mg/mmol (-0.5, 0.3)] were not significantly different. There was also no significant difference in the change in the ACR in the group as a whole. However, albuminuria at baseline was found in seven (10%) subjects. Five of these seven subjects had substantial improvements in ACR, ranging from 45 to 95%, with HAART use; three subjects had resolution of albuminuria. ACR at baseline significantly correlated with the baseline HIV-1 RNA level (r = 0.25; P = 0.04) and negatively with CD4 cell count (r = -0.25; P = 0.04).


CONCLUSIONS
Albuminuria in HIV-infected, treatment-naïve patients was found more frequently than expected and may be influenced by baseline immune status. Although we did not observe an effect of HAART on ACR during the first 64 weeks of therapy, we cannot exclude the possibility that HAART may be beneficial in those patients with significant albuminuria prior to treatment. Research in larger cohorts is required to investigate more definitively the associations between immune status, antiretroviral therapies and renal function in HIV-infected patients.
Gupta
Samir K
SK
Division of Infectious Diseases, Indiana University School of Medicine, Wishard Hospital, OPW-430, 1001 W. 10th Street, Indianapolis, IN 46202, USA. sgupta1@iupui.edu
Parker
Robert A
RA
Robbins
Gregory K
GK
Dubé
Michael P
MP
D000328:Adult; D000419:Albuminuria / Q000150:complications* / Q000188:drug therapy* / Q000652:urine; D023241:Antiretroviral Therapy, Highly Active; D002318:Cardiovascular Diseases / Q000209:etiology; D003404:Creatinine / Q000652:urine; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D003404:Creatinine