Albuminuria Is Associated with Traditional Cardiovascular Risk Factors and Viral Load in HIV-Infected Patients in Rural South Africa

<div><p>Context</p><p>As life expectancy improves among Human Immunodeficiency Virus (HIV) patients, renal and cardiovascular diseases are increasingly prevalent in this population. Renal and cardiovascular disease are mutual risk factors and are characterized by albuminuria. Understanding the interactions between HIV, cardiovascular risk factors and renal disease is the first step in tackling this new therapeutic frontier in HIV.</p><p>Methods</p><p>In a rural primary health care centre, 903 HIV-infected adult patients were randomly selected and data on HIV-infection and cardiovascular risk factors were collected. Glomerular filtration rate (eGFR) was estimated. Albuminuria was defined as an Albumin-Creatinine-Ratio above 30 mg/g. Multivariate logistic regression analysis was used to analyse albuminuria and demographic, clinical and HIV-associated variables.</p><p>Results</p><p>The study population consisted of 903 HIV-infected patients, with a median age of 40 years (Inter-Quartile Range (IQR) 34–48 years), and included 625 (69%) women. The median duration since HIV diagnosis was 26 months (IQR 12–58 months) and 787 (87%) received antiretroviral therapy. Thirty-six (4%) of the subjects were shown to have diabetes and 205 (23%) hypertension. In the cohort, 21% had albuminuria and 2% an eGFR <60 mL/min/1.73m². Albuminuria was associated with hypertension (adjusted odds ratio (aOR) 1.59; 95% confidence interval (CI) 1.05–2.41; <i>p</i><0.05), total cholesterol (aOR 1.31; 95% CI 1.11–1.54; <i>p</i><0.05), eGFR (aOR 0.98; 95% CI 0.97–0.99; <i>p</i><0.001) and detectable viral load (aOR 2.74; 95% CI 1.56–4.79; <i>p</i><0.001). Hypertension was undertreated: 78% were not receiving treatment, while another 11% were inadequately treated. No patients were receiving lipid-lowering medication.</p><p>Conclusion</p><p>Glomerular filtration rate was well conserved, while albuminuria was common amongst HIV-infected patients in rural South Africa. Both cardiovascular and HIV-specific variables were associated with albuminuria. Improved cardiovascular risk prevention as well as adequate virus suppression might be the key to escape the vicious circle of renal failure and cardiovascular disease and improve the long-term prognosis of HIV-infected patients.</p></div

Hypertensive Control in HIV-positive patients (N = 205).

<p>Included subjects from the cohort of 903 HIV-positive patients: 205 patients, previously diagnosed with hypertension or in whom hypertension was newly diagnosed. Hypertensive = systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg.</p

Diabetes Control in HIV-positive patients (N = 36).

<p>Included subjects from the cohort of 903 HIV-positive patients: 36 patients, previously diagnosed with diabetes or in whom a raised HbA1c was measured. Raised HbA1c = HbA1c > 6.5%.</p

Variables associated with albuminuria ^a in univariate and multivariate analysis in an unselected group of HIV-infected patients.

<p>Included subjects in multivariate analysis: 865. Number of subjects with albuminuria: 174.</p><p>*p-values are significant (p<0.05);</p><p>⁺ p-values between 0.05 and 0.10;</p><p>^Y Excluded due to collinearity with another variable.</p><p>^a Albuminuria: ACR>30 mg/g;</p><p>^b Large waist circumference: >94 cm men or > 80 cm women;</p><p>^c Diabetes mellitus: HbA₁c > 6.5% or use of diabetes medication;</p><p>^d Hypertension: Systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg or use of antihypertensive medication.</p><p>ACR = Albumine—Creatinine Ratio; ALT = alanine aminotransferase (mmol/l); aOR = adjusted odds ratio; ART = anti-retroviral treatment; BMI = Body Mass Index; 95% CI = 95% Confidence Interval; CKD-EPI = Chronic Kidney Disease—Epidemiology; CVE = cardiovascular event; eGFR = estimated glomerular filtration rate; HIV = Human Immunodeficiency Virus; LDL = Low-density lipoprotein; MDRD = Modification of Diet in Renal Disease; NNRTI = Non-nucleoside reverse-transcriptase inhibitors; PI-based = protease inhibitor-based; VL = viral load.</p><p>Variables associated with albuminuria <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136529#t002fn005" target="_blank">^a</a> in univariate and multivariate analysis in an unselected group of HIV-infected patients.</p

Initial full virological suppression (plasma HIV-1 RNA<50 copies/ml).

<p>Patients who switched following first-line treatment failure. N: number of patients at risk.</p

Baseline characteristics.

<p>N: number of patients, IQR: interquartile range, NRTI: nucleoside reverse transcriptase inhibitor, NNRTI: non-nucleoside reverse transcriptase inhibitor.</p

Virological response after start second-line. Cross-sectional analysis, OT.

<p>Patients who switched following first-line treatment failure.</p><p>N: Number of patients.</p

Clinical and immunological outcome at end of follow-up and after one year of second-line ART.

<p>Patients who switched following first-line treatment failure.</p><p>ITT: intention-to-treat analysis, OT: on-treatment analysis, N: number of patients, IQR: interquartile range.</p><p>Immunological failure was defined according to the WHO guidelines: a CD4 count after six months of therapy below 100 cells/mm3 or below the pre-therapy count, or a 50% decline from the on-treatment peak CD4 count value. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058526#pone.0058526-1" target="_blank">[1]</a></p

Virological outcome at end of follow-up; N = 191.

<p>Patients who switched following first-line treatment failure. N: number of patients, VL: plasma HIV-1 viral load. Full virological suppression: plasma HIV-1 RNA<50 copies/ml, low viral replication: 501000 copies/ml after initial VL<400 copies/ml, on-going viremia: plasma HIV-1 RNA never<400 copies/ml. Indefinite outcome: duration of follow-up <6 months without adequate virological response.</p