Alcohol consumption and neurocognitive deficits in people with well-treated HIV in Switzerland.

BACKGROUND: Hazardous alcohol consumption and HIV infection increase the risk of neurocognitive impairment (NCI). We examined the association between alcohol consumption and specific neurocognitive domain function in people with HIV (PWH) taking modern antiretroviral therapy. METHODS: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a prospective, longitudinal, multicentre and multilingual (French, German and Italian) study of patients aged ≥45 years old enrolled in the Swiss HIV Cohort Study (SHCS). Baseline data from 981 study participants were examined. Five neurocognitive domains were evaluated: motor skills, speed of information processing, attention/working memory, executive function and verbal episodic memory. NCI was examined as binary (presence/absence) and continuous (mean z-score) outcomes against Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) scores using logistic and linear regression models, respectively. RESULTS: Most participants (96.2%) had undetectable viral loads and 64% were aged >50 years old. Hazardous alcohol consumption was observed in 49.4% of participants and binge drinking in 4.2%. While alcohol consumption frequency and quantity were not associated with NCI, the practice of binge drinking was significantly associated with impaired motor skills and overall neurocognitive function in both binary (odds ratio, OR ≥2.0, P <0.05) and continuous (mean z-score difference -0.2 to -0.4, P ≤0.01) outcomes. A significant U-shaped distribution of AUDIT-C score was also observed for motor skills and overall neurocognitive function. CONCLUSIONS: In this cohort of PWH with well-controlled HIV infection, NCI was associated with the practice of binge drinking rather than alcohol consumption frequency or quantity. Longitudinal analysis of alcohol consumption and NCI in this population is currently underway.

The Impact of Immunosuppression on Chronic Kidney Disease in People Living With Human Immunodeficiency Virus: The D:A:D Study.

BACKGROUND: Relations between different measures of human immunodeficiency virus-related immunosuppression and chronic kidney disease (CKD) remain unknown. METHODS: Immunosuppression measures included baseline, current, time-lagged and nadir CD4, years and percentage of follow-up (%FU) with CD4 ≤200 cells/µL, and CD4 recovery. CKD was defined as confirmed estimated glomerular filtration rate <60 mL/minute/1.73 m2. RESULTS: Of 33 791 persons, 2226 developed CKD. Univariably, all immunosuppression measures predicted CKD. Multivariably, the strongest predictor was %FU CD4 ≤200 cells/µL (0 vs >25%; incidence rate ratio [IRR], 0.77 [95% confidence interval [CI], .68-.88]), with highest effect in those at low D:A:D CKD risk (IRR, 0.45 [95% CI, .24-.80]) vs 0.80 [95% CI, .70-.93]). CONCLUSIONS: Longer immunosuppression duration most strongly predicts CKD and affects persons at low CKD risk more.

A clinically useful risk-score for chronic kidney disease in HIV infection.

INTRODUCTION: Development of a simple, widely applicable risk score for chronic kidney disease (CKD) allows comparisons of risks or benefits of starting potentially nephrotoxic antiretrovirals (ARVs) as part of a treatment regimen. MATERIALS AND METHODS: A total of 18,055 HIV-positive persons from the Data on Adverse Drugs (D:A:D) study with >3 estimated glomerular filtration rates (eGFRs) >1/1/2004 were included. Persons with use of tenofovir (TDF), atazanavir (ritonavir boosted (ATV/r) and unboosted (ATV)), lopinavir (LPV/r) and other boosted protease inhibitors (bPIs) before baseline (first eGFR >60 ml/min/1.73 m(2) after 1/1/2004) were excluded. CKD was defined as confirmed (>3 months apart) eGFR <60. Poisson regression was used to develop a score predicting low (<0 points), medium (1-4 points) and high (>5 points) risk of developing CKD. Increased incidence of CKD associated with starting ARVs was modelled by including ARVs as time-updated variables. The risk score was externally validated on two independent cohorts. RESULTS: A total of 641 persons developed CKD during 103,278.5 PYFU (incidence 6.2/1000 PYFU, 95% CI 5.7-6.7). Older age, intravenous drug use, HCV+ antibody status, lower baseline eGFR, female gender, lower CD4 nadir, hypertension, diabetes and cardiovascular disease predicted CKD and were included in the risk score (Figure 1). The incidence of CKD in those at low, medium and high risk was 0.8/1000 PYFU (95% CI 0.6-1.0), 5.6 (95% CI 4.5-6.7) and 37.4 (95% CI 34.0-40.7) (Figure 1). The risk score showed good discrimination (Harrell's c statistic 0.92, 95% CI 0.90-0.93). The number needed to harm (NNTH) in patients starting ATV or LPV/r was 1395, 142 or 20, respectively, among those with low, medium or high risk. NNTH were 603, 61 and 9 for those with a low, medium or high risk starting TDF, ATV/r or bPIs. The risk score was externally validated on 2603 persons from the Royal Free Hospital clinic cohort (94 events, incidence 5.1/1000 PYFU; 95% CI 4.1-6.1) and 2013 persons from the control arms of SMART/ESPRIT (32 events, incidence 3.8/1000 PYFU; 95% CI 2.5-5.1). External validation showed consistent CKD rates across risk groups (Figure 2). INTERPRETATION: Traditional and HIV-related risk factors were predictive of CKD; all are routinely available, making the risk score easy to incorporate into clinical practise and of direct relevance for clinical decision making. NNTH in persons starting potentially nephrotoxic ARVs at high risk of CKD were low, and alternative ARVs may be more appropriate.

Predictors of advanced chronic kidney disease and end-stage renal disease in HIV-positive persons.

OBJECTIVES: Whilst several antiretroviral drugs have been associated with moderate chronic kidney disease (CKD), their contribution to advanced CKD and end-stage renal disease (ESRD) remain unknown. DESIGN: D:A:D participants with at least three estimated glomerular filtration rates (eGFR) after February 2004 were followed until the first of advanced CKD (confirmed eGFR ≤ 30 ml/min, ≥3 months apart), ESRD (dialysis ≥3 months/ transplantation), 6 months after last visit or February 2012. METHODS: Poisson regression was used to assess risk factors for advanced CKD/ESRD including exposure to potential nephrotoxic antiretroviral drugs and antiretroviral drug discontinuation rates according to latest eGFR. RESULTS: Among 35 192 persons contributing 200 119 person years of follow-up (PYFU), 135 (0.4%) developed advanced CKD (n = 114)/ESRD (n = 21); incidence rate = 0.67 [95% confidence interval (CI), 0.56-0.79]/1000 PYFU. Tenofovir (TDF) was particularly frequently discontinued as eGFR declined. After adjustment, those previously exposed but currently off TDF had similar advanced CKD/ESRD rate ratios compared with those unexposed [1.00 (95% CI, 0.66-1.51)], while those currently on TDF had reduced rates [0.23 (95% CI, 0.13-0.41)]. No consistent associations with other antiretroviral drugs were seen. Results were robust after time-lagging antiretroviral drug exposure, stratifying by baseline eGFR, and allowing for competing risks. Other predictors were diabetes, hypertension, baseline eGFR, smoking and current CD4 cell count. The incidence rate in nonsmokers with baseline eGFR > 60 and no diabetes or hypertension was 0.16 (95% CI 0.09-0.26)/1000 PYFU. CONCLUSION: Neither current nor recent antiretroviral drug use predicted advanced CKD/ESRD during 6 years median follow-up in a large, heterogenenous and primarily white cohort. TDF discontinuation rates increased with decreasing eGFR, leaving a selected group still on TDF at lower advanced CKD/ESRD risk. Traditional renal risk factors and current CD4 cell count were the strongest advanced CKD/ESRD predictors.