Background:  Proteinuria is a marker for progressive HIV-related chronic kidney disease. However, predictors of proteinuria in the HAART era are unknown.

Methods:  Urine protein to creatinine ratios (P/Cr) were measured annually since 2002 in the ALLRT, a longitudinal observational cohort study of subjects prospectively randomized to receive HAART regimens or treatment strategies in select AIDS Clinical Trials Group (ACTG) trials. Odds of having clinically significant proteinuria, defined as a P/Cr >0.2, at each measurement were assessed using multivariable general estimating equations.

Results:  Initial P/Cr was measured at least once in 2827 ALLRT participants (83% male, 28% black, 5% reported history of diabetes mellitus, 16% reported history of hypertension, 67% were antiretroviral (ARV) -naïve at baseline, 10% were hepatitis C virus (HCV) antibody⁺, and 4% were hepatitis B virus (HBV) antigen⁺. Baseline characteristics included median (IQR) estimated glomerular filtration rate (eGFR) (98.4; 85.6 to 115.6 mL/min/1.73m²), age (39, 33 to 46 years), CD4 count (233, 98 to 385 cells/µL), and log₁₀HIV-1 RNA (4.64, 4.01 to 5.27 copies/mL). Median (IQR) time from baseline to initial P/Cr was 680 (314 to 1652) days, and median (IQR) number of P/Cr measurements was 3 (2 to 4). Median (IQR) initial P/Cr was 0.095 (0.065 to 0.161); 20% had P/Cr >0.2. There was a statistically significant (p = 0.02 for slope≠0) overall improvement in P/Cr of –0.033 (95%CI –0.060 to –0.019)/year. Achieving a viral load <400 copies/mL was associated with lower odds of P/Cr >0.2 (OR 0.91; 95%CI 0.76 to 0.94; p = 0.01); this association was more pronounced in those with baseline CD4 cell counts <200/µL (OR 0.73; 95%CI 0.55 to 0.0.98; p = 0.04). Other predictors (OR, 95%CI) included older age (1.02; 1.01 to 1.03; p <0.01), black race (1.25; 1.06 to 1.50; p = 0.01), lower baseline estimated GFR (0.99; 0.98 to 0.99; p <0.01), higher baseline log₁₀ HIV-1 RNA level (1.15; 1.05 to 1.26; p <0.01), ARV-naive at baseline (0.50; 0.41 to 0.62; p <0.01), reported history of diabetes [2.14; 1.54 to 2.99; p <0.01), reported history of hypertension (1.26; 1.03 to 1.54; p = 0.03), HCV antibody⁺ (1.28; 0.99 to 1.66; p = 0.07).

Conclusions:  P/Cr decreased over time in this large HIV-infected cohort. Viral suppression to <400 copies/mL resulted in reduced odds of clinically significant proteinuria, an effect that was more pronounced with lower baseline CD4 counts. Several non-HIV factors also exist to identify those more likely to have proteinuria and who should be treated aggressively to prevent progressive kidney disease.