The effects of HIV type-1 viral suppression and non-viral factors on quantitative proteinuria in the highly active antiretroviral therapy era

Background Proteinuria is associated with progressive renal disease and overall mortality in HIV-infected patients; however, the prevalence and correlates of quantitative pro-teinuria in the highly active antiretroviral therapy era are unknown. Methods Spot urine protein to creatinine (P/Cr) ratios, an accepted measure of quantitative daily proteinuria, were measured annually since 2002 in participants of the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort. We used linear regression models with general estimating equations to identify factors associated with the abnormal P/Cr thresholds of ≥0.2 and ≥1.0. Results Of the 2,857 participants (most of whom were receiving antiretroviral therapy) analysed, 16% and 3% had P/Cr levels ≥0.2 and ≥1.0, respectively, at first measurement. P/Cr levels did not change during a median follow-up of 3 years (interquartile range 2–4). Factors associated with P/Cr≥0.2 at any measurement included greater age, lower glomerular filtration rate, female sex, antiretroviral therapy prior to entry into parent randomized trial, HIV type-1 RNA level ≥400 copies/ ml, lower CD4+ T-cell count and history of hypertension, diabetes or hepatitis C coinfection (all P<0.04). Black race and higher non-high-density lipoprotein cholesterol levels were associated with P/Cr levels ≥1.0, but not with P/ Cr levels ≥0.2. Hepatitis B coinfection and current use of adefovir, indinavir and tenofovir were not associated with either of the P/Cr thresholds. Conclusions Both HIV-1 and non-HIV-1-related factors are associated with abnormal levels of proteinuria and identify those who are at a greater risk of worse clinical outcomes. Several of these factors are differentially associated with lower and higher proteinuria thresholds.