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

Ryom, Lenea; Mocroft, Amandab; Kirk, Olea; Ross, Michaelc; Reiss, Peterd; Fux, Christophe A.e; Morlat, Philippef; Moranne, Olivierg; Smith, Coletteb; El-Sadr, Wafaah; Law, Matthewi; Lundgren, Jens D.a

doi: 10.1097/QAD.0000000000000042
Clinical Science

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.

aCopenhagen HIV Programme, University of Copenhagen, Faculty of Health and Medical Sciences and Epidemiklinikken M5132, Copenhagen University Hospital/Rigshospitalet, Copenhagen, Denmark

bResearch Department of Infection and Population Health, UCL, London, UK

cDivision of Nephrology, Mount Sinai School of Medicine, New York, USA

dAcademic Medical Center, University of Amsterdam, and Stichting HIV Monitoring, The Netherlands

eClinic for Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, Switzerland

fService de médecine interne et maladies infectieuses, Hôpital Saint-André, CHU de Bordeaux

gNephrology Department, Public Health Department, CHU Nice, France

hICAP-Columbia University and Harlem Hospital, New York, USA

iKirby Institute, Sydney, Australia.

Correspondence to Lene Ryom, MD, Copenhagen HIV Programme, University of Copenhagen, Faculty of Health Sciences The Panum Institute/Building 21.1 Blegdamsvej 3B, 2200 Copenhagen, Denmark. Tel: +45 35 45 57 57; fax: +45 35 45 57 58; e-mail:

Received 9 April, 2013

Revised 20 August, 2013

Accepted 21 August, 2013

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HIV-positive individuals are potentially at high risk of renal disease due to the harmful combination of exposure to HIV itself [1,2], co-infections [3], immune suppression [4], use of nephrotoxic drugs [5,6] and various traditional renal risk factors such as diabetes, smoking and hypertension [7,8]. Earlier studies have shown that HIV-positive individuals on combination antiretroviral treatment (cART) preserve renal function better than those not on cART [9,10]. cART has further been shown to reduce the incidence of HIV-associated nephropathy (HIVAN) [11], and its discontinuation has been associated with progression to end-stage renal disease (ESRD) [12]. In addition, several studies, including work from the Data collection on Adverse events of Anti-HIV Drugs Study (D:A:D), have identified an association between exposure to several antiretroviral drugs including tenofovir (TDF), ritonavir-boosted atazanavir (ATV/r) and lopinavir/r (LPV/r) and increased risk of moderate levels of renal impairment including moderate chronic kidney disease (CKD) [6,9,13–17]. The independent contribution of these antiretrovirals towards the development of more severe CKD levels such as advanced CKD and ESRD has not been explored in detail.

Most studies of more severe CKD levels in HIV-positive individuals have focused on populations of African ancestry, where the high ESRD incidence is partly explained by a genetic predisposition related to polymorphisms at the APOL1/MYH9 locus rendering them at high risk of HIVAN [1,2,7]. In contrast, the factors contributing to ESRD in HIV-positive individuals of nonAfrican ancestry are less well understood.

The aim of this analysis was to assess predictors of advanced CKD and ESRD in a large heterogeneous cohort, focusing on exposure to antiretroviral drugs with known nephrotoxic potential.

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Study population

The D:A:D study is a prospective cohort collaboration established in 1999 following more than 49 000 HIV-1-positive persons in Europe, USA and Australia; details have been published previously [18]. Data on predefined clinical events including ESRD, myocardial infarction, stroke, invasive cardiovascular procedures and death is collected in real-time during routine clinical care, validated centrally and regularly monitored. In addition, information including demographic factors, ART, laboratory values, cardiovascular risk factors and AIDS events is collected electronically at enrolment and every 6 months.

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Outcome definitions

The primary endpoint investigated was advanced CKD or ESRD, as these conditions likely share a common risk profile. Advanced CKD was defined according to the National Kidney Foundation as two consecutive measurements more than 3 months apart of estimated glomerular filtration rate (eGFR) ≤30 ml/min [19]. ESRD events are reported to the D:A:D coordinating office using a designated case report form, and defined as dialysis lasting at least 3 months or performance of renal transplantation (more information at The ESRD form also contains information on the presumed underlying disease aetiology. All ESRD events are centrally adjudicated blinded to the patient's ART and reviewed by an independent nephrologist.

The Cockcroft–Gault equation, without correction for body surface area [20,21], was used to calculate creatinine clearance, referred to as eGFR in this analysis. The choice of the Cockcroft–Gault equation was based on restrictions on ancestry information in several of the participating cohorts.

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Statistical methods

This analysis included persons under follow-up with at least three eGFR measurements after February 2004 (the date that systematic creatinine collection began) and without prevalent advanced CKD or ESRD at baseline.

Individuals were followed from baseline (first eGFR after February 2004) until the first of advanced CKD, ESRD, 6 months after the last clinical visit or February 2012.

Incidence rates of advanced CKD/ESRD overall and stratified by the presence of factors significant in multivariate analysis were calculated per 1000 person years of follow-up (PYFU). Kaplan–Meier estimation was used to determine the proportions progressing to advanced CKD/ESRD over time. Poisson regression models were used to investigate antiretroviral drug discontinuation rates in relation to the latest (i.e. current) eGFR level, and to quantify the relationship between advanced CKD/ESRD and exposure to known nephrotoxic antiretroviral drug as well as other potential risk factors.

Exposure to individual antiretroviral drugs was investigated by inclusion of the following agents with a previously reported nephrotoxic potential: TDF, ATV/r, ATV, LPV/r, and other boosted protease inhibitors (other PI/r) [6,9,13–17,22]. Indinavir use after 2004 was limited and its use was added only to account for possible confounding.

A number of exploratory analyses were carried out to determine the best way to fit antiretroviral drug exposure. For the primary model antiretroviral drug exposure was fitted categorically; never exposed, exposed and currently on drug, exposed and currently off drug.

Models were adjusted for antiretroviral drug exposure, non-antiretroviral risk factors and potential confounders of known relevance for renal impairment; all variables which changed after baseline were included as time-updated values in the primary analysis. Models were adjusted for demographic variables (age, sex, ethnicity and enrolment cohort), traditional renal risk factors [smoking status, hypertension (blood pressure >150/100 mmHg or use of antihypertensive treatment), diabetes (use of antidiabetic treatment or verification in a case report form [8])], cardiovascular events (CVE; myocardial infarction, invasive cardiovascular procedure or stroke verified in a case report form [18]) and HIV-related factors (HIV-transmission group, nadir and current CD4+ cell count, viral load, prior AIDS, hepatitis B (HBV): positivity by HBsAg positive, HBeAg positive or HBV-DNA positive/anti-HBe positive and hepatitis C (HCV): positivity by anti-HCV and HCV-RNA positive/unknown).

Interactions between current CD4+ cell count and the most common traditional renal risk factors such as diabetes and hypertension [23–25] were also investigated.

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Sensitivity analyses

Several sensitivity analyses were performed to investigate the robustness of our findings. Antiretroviral drug use was time-lagged by 3, 6 and 12 months to investigate whether any potential associations were missed by assuming antiretroviral drug toxicity ended when exposure was discontinued. A second sensitivity analysis, stratified by baseline eGFR > or ≤60 ml/min, assessed if there was any differences in potential antiretroviral drug associations among those with impaired eGFR.

An additional sensitivity analysis with an endpoint of all-cause mortality was conducted using Poisson regression models to allow for competing risks.

All statistical analyses were carried out using SAS version 9.3 (Statistical Analysis Software, Cary, North Carolina, USA).

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A total of 49 731 persons were under follow-up in D:A:D. After exclusion of 81 persons (0.2%) with prevalent advanced CKD, 17 with ESRD (<0.1%), 5260 without follow-up after 2004 (10.6%) and 9181 with insufficient number of eGFR measurement (18.6%), 35 192 persons were included. Those included had a higher viral load, were less likely to have had prior AIDS, CVE or HCV, and less likely to be intravenous drug users (IDUs), current smokers, diabetic, or off ART.

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Patient characteristics

Among those included 48.1% were whites and 43.0% of unknown ancestry. 73.9% were men, and the median age at baseline was 41 (inter-quartile range, IQR 35–48) years. The median CD4+ cell count was 436 (IQR 289–620) cells/μl and the majority (74.0%) had a normal baseline eGFR according to the National Kidney Foundation Classification [19] (Table 1).

Table 1

Table 1

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Advanced chronic kidney disease/end-stage renal disease incidence and characteristics

A total of 135 persons (0.4%) developed advanced CKD (n = 114)/ESRD (n = 21) during 200 119 PYFU, with an overall incidence rate of 0.67 [95% confidence interval (95% CI), 0.56–0.79]/1000 PYFU. The median length of follow-up in the study was 6.2 years (IQR 4.1–7.6). The incidence rate for those at low risk of renal disease that is with baseline eGFR more than 60 and no diabetes, hypertension or current smoking was 0.16 (95% CI, 0.09–0.26)/1000 PYFU. Furthermore, individuals developing ESRD were older than those developing advanced CKD [median age 59 (IQR 48–69) vs. 48 (IQR 43–54) years].

Of the 21 persons with ESRD, 20 received continuous dialysis (hemodialysis n = 16 and peritoneal dialysis n = 4) and one had a renal transplantation. The underlying aetiology and histology findings were HIVAN (n = 4), tubulo/interstitial nephritis (n = 3), IgA-nephropathy (n = 2), mesangio/membrano-proliferative glomerulonephritis (n = 2), amyloidosis (n = 1), diabetic glomerulo-sclerosis (n = 1), global glomerulosclerosis (n = 1), unspecified glomerulonephritis (n = 1), obstruction/renal-TB (n = 1), polycystic kidney disease (n = 1) and unknown (n = 4). Fourteen of the 21 persons (66.7%) had had a biopsy-verified diagnosis.

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Progression to advanced chronic kidney disease/end-stage renal disease

At 5 years after baseline an estimated 0.32% (95% CI, 0.26–0.38%) had progressed to advanced CKD/ESRD using Kaplan-Meier estimation (Fig. 1). A higher proportion developed advanced CKD at 5 years [0.26% (95% CI, 0.20–0.32%)] compared with ESRD [0.06% (95% CI, 0.03–0.09%)]. Among those with baseline eGFR ≤60 ml/min, 6.6% (95% CI, 5.0–8.2%) were estimated to have progressed to advanced CKD/ESRD at 5 years compared with only 0.07% (95% CI, 0.03–0.10%) for those with baseline eGFR >90 ml/min.

Fig. 1

Fig. 1

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Antiretroviral drugs switches

The adjusted rates of switching away from all included antiretroviral drugs increased as eGFR declined, but was especially marked for TDF (Fig. 2).

Fig. 2

Fig. 2

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Associations of antiretroviral drug use with advanced chronic kidney disease/end-stage renal disease

In fully adjusted models, individuals previously exposed, but currently off TDF had similar rates of advanced CKD/ESRD compared with individuals unexposed to TDF [adjusted incidence rate ratio 1.00 (95% CI, 0.66–1.51)]. In contrast, individuals exposed, and currently on TDF had a reduced rate of advanced CKD/ESRD compared with those unexposed [0.23 (95% CI, 0.13–0.41)] (Table 2).

Table 2

Table 2

For all other included antiretroviral drugs no consistent or significant associations were seen between their current or previous use and advanced CKD/ESRD in adjusted models (Table 2). Neither recent antiretroviral drug use (i.e. the time-lagged analysis) nor stratifying by baseline eGFR ≤60 ml/min altered these findings. The association between ATV/r use and advanced CKD/ESRD was significant among those with eGFR ≤60 ml/min, but the confidence intervals overlapped with those of our primary analysis and an analysis of interaction between ATV/r and eGFR > or ≤60 ml/min was not statistically significant. Analyses treating death as a competing risk were highly consistent (data not shown).

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Association of non-antiretroviral drug risk factors with advanced chronic kidney disease/end-stage renal disease

Other risk factors significantly associated with advanced CKD/ESRD were diabetes [3.29 (95% CI, 2.18–4.98)], hypertension [2.48 (95% CI, 1.70–3.62)], lower baseline eGFR [2.05 (95% CI, 1.86–2.26)/10 ml per min], current vs. nonsmokers [1.79 (95% CI, 1.08–2.97)] and lower current CD4+ cell count [1.37 (95% CI, 1.19–1.56)/halving] (Fig. 3). The association between current CD4+ cell count and advanced CKD/ESRD was further explored and revealed a strong gradient with a crude incidence rate of 2.42 (95% CI, 1.60–3.25)/1000 PYFU for current CD4+ cell counts ≤200 cells/μl and 0.38 (95% CI, 0.2726–0.50) for current CD4+ cell count >500 cells/μl.

Fig. 3

Fig. 3

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This is the largest long-term study to date to investigate predictors of advanced CKD/ESRD and associations with antiretroviral drug previously shown to be associated with moderate CKD [6,9,14–17]. With a median follow-up exceeding 6 years, we found no strong or statistically significantly increased advanced CKD/ESRD incidence for current or recent antiretroviral drug exposure.

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The observed relatively low incidence of advanced CKD/ESRD in D:A:D is between two and 14 times lower than the estimates reported in US studies among HIV-positive persons, and likely reflects the demographic constitution (primarily relatively young, Caucasian individuals) of the D:A:D study population, the relatively low prevalence of several common renal risk factors such as diabetes and hypertension [7,9,24,26] and follow-up in the current modern cART era.

Rates of progression from moderate CKD to ESRD in the general HIV-negative population are reported to be more than five times lower during a similar duration of follow-up compared with rates seen among the D:A:D study participants in this study [35].

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Antiretroviral drug associations with advanced chronic kidney disease/end-stage renal disease

Although associations between several antiretroviral drugs and moderate CKD levels have been confirmed in numerous studies [6,9,14–17], few prospective studies have investigated these associations with more severe CKD. Bansi et al. found no association between cART status (binary fitted) and HIV-associated ESRD among persons of primarily African ancestry in a large UK study with follow-up until 2007 [27]. Similar findings were reported from other European and US studies, although these differed in study population, antiretroviral drugs and endpoints included, and were underpowered to explore antiretroviral drug associations in detail [9,28]. This analysis is therefore the first to provide a comprehensive investigation of the association between potentially nephrotoxic antiretroviral drugs and severe levels of CKD.

There are a number of potential explanations for the lack of an observed antiretroviral drug association with advanced CKD/ESRD in this analysis.

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We showed that switches away from antiretroviral drugs with nephrotoxic potential were increasingly common at declining eGFR levels, indicating appropriate clinical assessment and interventions for at-risk individuals. The antiretroviral drugs in use at or around the time of advanced CKD/ESRD are highly likely to be confounded by indication. In particular, persons remaining on TDF with severely impaired eGFR most likely reflect a highly selected group with a more favourable renal risk profile compared with those never exposed to TDF.

Sensitivity analyses using recent and cumulative antiretroviral drug exposure were also performed, without revealing any consistently clear associations. Clinical management of persons with declining eGFR make studying associations between antiretroviral drug use and advanced CKD/ESRD difficult. The possibility that such relations exists in populations without access to regular eGFR screening can therefore not be excluded.

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Follow-up duration

Urolithiasis is known to predict a two-fold increased ESRD hazard in the general population [29]. As several antiretroviral drugs including ATV/r are known for their potential to cause urolithiasis [30], one would expect to eventually see an association between these antiretroviral drugs and ESRD. In this and other studies [9,28], we were, however limited by several of these antiretroviral drugs only being introduced into care more recently (LPV/r in 2000 [31], TDF in 2001 [32] and ATV in 2003 [33]).

In a recent D:A:D analysis, Smith et al. [34] found no indication of increased mortality rates over time related to renal disease. The fact that the observed associations between certain antiretroviral drugs and moderate CKD levels [6,9,14–17] does not currently translate into either advanced CKD/ESRD nor mortality may reflect appropriate clinical management, or that longer follow-up among those developing moderate CKD is required for such relationships to emerge.

We can therefore not rule out that such clinical issues with use of antiretroviral drugs may arise once these drugs have been used more extensively and in HIV-populations with higher underlying risk of renal impairment than currently seen in D:A:D.

Finally, it also may be possible that the overall contribution of these antiretroviral drugs on CKD is only modest and therefore not significant contributors to advanced CKD/ESRD.

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Other factors associated with advanced chronic kidney disease/end-stage renal disease

Current CD4+ cell count is a well described predictor of moderate and advanced CKD/ESRD [4,6,9,24,27,28]. It is a common belief that chronic inflammation plays a central role for this association, although many unanswered questions on the exact underlying pathogenesis remain [4]. Maintaining cART adherence and high levels of immune function over time therefore also remains crucial for HIV-positive individuals to minimize the risk of severe levels of CKD. Interestingly, neither nadir CD4+, viral load or prior AIDS was significantly associated with advanced CKD/ESRD after accounting for other HIV-related factors in particular the current CD4+ cell count. Other studies have identified both higher viral load and prior AIDS as risk factors for ESRD [7,9,24], but adjusting for CD4+ cell count only at baseline in such studies and our generally well treated study population with a relatively low proportion of persons of known African ancestry may explain these differences [1,2,7,27].

Diabetes and hypertension are among the most common general causes for ESRD [23–25]. The strong associations seen in this analysis was somewhat higher than found in another HIV-study [24], but in similar ranges as in the background population [25,36]. Medapalli et al. [37] found evidence that the combination of HIV and diabetes significantly increased risk of progressive CKD. In our analysis, we did not find an interaction between current CD4+ cell count, diabetes or hypertension (all P > 0.1). Smoking is seldom considered as a potential renal risk factor in studies among HIV-positive individuals [7,24,27,38], but our finding is consistent with observations in the general population [25,36]. These findings, together with the extremely low incidence in persons without diabetes, hypertension or smoking highlight the need of a continued focus on diagnosing and treating modifiable risk factors for CKD in HIV-positive individuals. In contrast to many other studies in both HIV-positive and negative individuals, we found no significant association with CVE after accounting for other traditional risk factors [24,28,36]. Not all of these other studies required equally strong evidence of CVE, which in D:A:D are centrally adjudicated and reviewed by a cardiologist. Conversely, the prevalence of CVE at baseline in our analysis was relatively low.

IDU as mode of HIV-transmission was marginally associated with advanced CKD/ESRD in our analysis, whilst there was no association with HCV co-infection. This contrasts with what has been shown by others [9,24,38] and may be related to the relatively high proportions of persons with an unknown HCV status in our analysis.

Baseline eGFR was, as expected, a strong advanced CKD/ESRD predictor [9,24,28], and underlines its continued value for screening. Although age traditionally predicts moderate CKD [39], it was not associated with advanced CKD/ESRD after adjusting for eGFR, which declines proportionally with age and captures some of this effect. Others have reported similar findings in both HIV-positive and negative populations, possibly reflecting the competing risk of death for advanced CKD/ESRD among older persons with low eGFR [27,40].

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Strengths and limitations

The major strength of this study, compared to others, is its size, that it is based on lengthy follow-up in a recent cART era, includes other renal disorders than HIVAN, includes persons of various ethnicities, uses centrally adjudicated exploratory variables and outcomes and assesses association with individual antiretroviral drugs.

The limitations of our study should also be considered. As advanced CKD/ESRD takes a relatively long time to develop and is relatively rare, longer follow-up may be required to fully understand the relationship with long-term antiretroviral drug exposure. The reference category used for antiretroviral exposure was those never having started the individual antiretroviral drug of interest. For the PIs included in this analysis, this category would, therefore potentially also include persons with exposure to other PIs with a potentially different advanced CKD/ESRD risk (i.e. for LPV/r persons with previous ATV/r exposure). Because of the comparatively small number of events and cross over between categories, we were unfortunately not able to stratify the ‘never started’ categories further to investigate such trends.

In addition, we could not adjust for other nephrotoxic non-antiretroviral drugs, presence of proteinuria and a family history of CKD, which may represent unmeasured confounding. Exclusion due to no follow-up after 2004 and inadequate number of eGFR measurements may have introduced selection bias. Excluded persons were more likely to be current smokers, have diabetes or CVE, with an expected higher advanced CKD/ESRD incidence. A relatively high proportion of persons with unknown HCV status may have reduced our ability to show an association with advanced CKD/ESRD as found by others [9,24,38]. Finally, Caucasians (both HIV-positive and negative) have a lower ESRD incidence compared with individuals of African ancestry [26,27,41], possibly related to less aggressive disease progression [26,41]. Unfortunately, restrictions on collection on ancestry information in a number of participating cohorts limited our power to investigate this.

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This is the largest study to date with long-term follow-up addressing the clinical impact of suspected nephrotoxic antiretroviral drugs on severe levels of chronic renal impairment. Neither current nor recent antiretroviral drug use was associated with advanced CKD/ESRD. Our findings suggest that appropriate clinical management of persons with decreasing eGFR, including switching away from antiretroviral drugs with nephrotoxic potential, may explain the lack of such associations, and thereby complicates any such analyses. We cannot exclude that such associations may well be demonstrated in populations without access to regular eGFR screening and with more extensive antiretroviral drug use in populations with higher underlying renal risks. The main determinants of advanced CKD/ESRD were traditional renal risk factors and lower current CD4+ cell count.

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Author contributions: L.R., A.M., O.K. and J.D.L. developed the initial study protocol. L.R. performed study coordination and prepared the datasets for analysis. A.M. performed the statistical analysis and L.R. prepared the initial draft of the manuscript. All authors have provided input to the analyses, have contributed with data, have participated in the development of the manuscript and have seen and approved the final version.

Participating cohorts in D:A:D: Aquitaine (France), CPCRA (USA), Nice (France), ATHENA (The Netherlands), EuroSIDA (Europe, Israel and Argentina), SHCS (Switzerland), AHOD (Australia), HIV-BIVUS (Sweden), St. Pierre Brussels Cohort (Belgium), BASS (Spain), The ICONA Foundation (Italy).

D:A:D Steering Committee: Names marked with*, Chair with # Members of the D:A:D SC from the HAART-OC: B. Powderly*, N. Shortman*, G. Reilly*, C. Moecklinghoff*, X. Franquet*, D:A:D Central Coordination: L. Ryom, C.A. Sabin*, D.A. Kamara, C. Smith, A. Phillips*, A. Mocroft, J. Tverland, J. Nielsen, J.D. Lundgren#; D:A:D data managers: R. Salbøl Brandt (coordinator), M. Rickenbach, I. Fanti, E. Krum, M. Hillebregt, S. Geffard, A. Sundström, M. Delforge, E. Fontas, F. Torres, H. McManus, S. Wright, J. Kjær. Verification of endpoints: A. Sjøl (CVD primary endpoint), P. Meidahl (oncology), J. Helweg-Larsen (hematology), J. Schmidt Iversen (nephrology) D:A:D renal working group: L. Ryom, A. Mocroft, O. Kirk, D.A. Kamara, C. Smith, P. Reiss, M. Ross, C.A. Fux, P. Morlat, O. Moranne, and J.D. Lundgren.

The members of the 11 Cohorts are as follows: ATHENA (AIDS Therapy Evaluation Project Netherlands): Central coordination: P. Reiss*, S. Zaheri, M Hillebregt, L. Gras; Participating physicians (¤Site coordinating physicians): Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam: Prof. dr J.M. Prins¤, Prof. dr T.W. Kuijpers, Dr H.J. Scherpbier, Dr J.T.M. van der Meer, Dr F.W.M.N. Wit, Dr M.H. Godfried, Prof. dr P. Reiss¤*, Prof. dr T. van der Poll, Dr F.J.B. Nellen, Prof. dr J.M.A. Lange, Dr S.E. Geerlings, Dr M. van Vugt, Dr D. Pajkrt, Drs J.C. Bos, Drs M. van der Valk, Dr M.L. Grijsen, Dr W.J. Wiersinga, Dr A. Goorhuis, Dr J.W.R. Hovius. Academisch Ziekenhuis Maastricht, Maastricht: Dr S. Lowe¤, Dr A. Oude Lashof, Dr D. Posthouwer. Catharina-ziekenhuis, Eindhoven: Dr M.J.H. Pronk¤, Dr H.S.M. Ammerlaan. Erasmus Medisch Centrum, Rotterdam: Dr M.E. van der Ende¤, Dr T.E.M.S. de Vries-Sluijs, Dr C.A.M. Schurink, Dr J.L. Nouwen, Dr A. Verbon, Dr B.J.A. Rijnders, Dr E.C.M. van Gorp, Dr M. van der Feltz. Erasmus Medisch Centrum–Sophia, Rotterdam: Dr G.J.A. Driessen, Dr A.M.C. van Rossum. Flevoziekenhuis. Almere: Dr J. Branger¤. HagaZiekenhuis, Den Haag: Dr E.F. Schippers¤, Dr C. van Nieuwkoop, Dr E.P. van Elzakker. Isala Klinieken, Zwolle: Dr P.H.P. Groeneveld¤, Dr J.W. Bouwhuis. Kennemer Gasthuis: Dr R. Soetekouw¤, Prof. dr R.W. ten Kate. Leids Universitair Medisch Centrum, Leiden: Dr F.P. Kroon¤, Prof. dr J.T. van Dissel, Dr S.M. Arend, Dr M.G.J. de Boer, Dr H. Jolink, Dr H.J.M. ter Vollaard, Dr M.P. Bauer. Maasstadziekenhuis, Rotterdam: Dr J.G. den Hollander¤, Dr K. Pogany. Medisch Centrum Alkmaar, Alkmaar: Dr G. van Twillert¤, Dr W. Kortmann¤, Dr J.W.T. Cohen Stuart, Dr B.M.W. Diederen. Medisch Centrum Haaglanden, Den Haag: Dr E.M.S. Leyten¤, Dr L.B.S. Gelinck. Medisch Spectrum Twente, Enschede: Dr G.J. Kootstra¤, Drs C.E. Delsing. Onze Lieve Vrouwe Gasthuis, Amsterdam: Prof. dr K. Brinkman¤, Dr W.L. Blok, Dr P.H.J. Frissen, Drs W.E.M. Schouten, Dr G.E.L. van den Berk. Sint Elisabeth Ziekenhuis, Tilburg: Dr M.E.E. van Kasteren¤, Dr A.E. Brouwer. Sint Lucas Andreas Ziekenhuis, Amsterdam: Dr J. Veenstra¤, Dr K.D. Lettinga. Slotervaartziekenhuis, Amsterdam: Dr J.W. Mulder¤, Dr S.M.E. Vrouenraets, Dr F.N. Lauw. Stichting Medisch Centrum Jan van Goyen, Amsterdam: Dr A. van Eeden¤, Dr D.W.M. Verhagen. Universitair Medisch Centrum Groningen, Groningen: Dr H.G. Sprenger¤, Dr R. Doedens, Dr E.H. Scholvinck, Dr S. van Assen, Dr W.F.W. Bierman. Universitair Medisch Centrum Sint Radboud, Nijmegen: Dr P.P. Koopmans¤, Dr M. Keuter, Dr A.J.A.M. van der Ven, Dr H.J.M. ter Hofstede, Dr A.S.M. Dofferhoff, Dr A. Warris, Dr R. van Crevel. Universitair Medisch Centrum Utrecht, Utrecht: Prof. dr A.I.M. Hoepelman¤, Dr T. Mudrikova, Dr M.M.E. Schneider, Dr P.M. Ellerbroek, Dr J.J. Oosterheert, Dr J.E. Arends, Dr M.W.M. Wassenberg, Dr R.E. Barth. Vrije Universiteit Amsterdam, Amsterdam: Dr M.A. van Agtmael¤, Dr R.M. Perenboom, Drs F.A.P. Claessen, Dr M. Bomers, Dr E.J.G. Peters. Wilhelmina Kinderziekenhuis, Utrecht: Dr S.P.M. Geelen, Dr T.F.W. Wolfs, Dr L.J. Bont. Ziekenhuis Rijnstate, Arnhem: Dr C. Richter¤, Dr J.P. van der Berg, Dr E.H. Gisolf. Admiraal De Ruyter Ziekenhuis, Vlissingen: Drs M. van den Berge¤, Drs A. Stegeman. Medisch Centrum Leeuwarden, Leeuwarden: Dr M.G.A. van Vonderen¤, Dr D.P.F. van Houte. Medisch Centrum Zuiderzee, Lelystad: Dr S. Weijer¤, Dr R. el Moussaoui. Sint Elisabeth Hospitaal, Willemstad - Curaçao: Dr C. Winkel, Dr F. Muskiet, Dr Durand, Dr R. Voigt.

Aquitaine Cohort (France) Principal investigator: Pr F. Dabis* Scientific committee: Prs F. Bonnet, F. Dabis*, M. Dupon, G. Chêne, D. Breilh, H. Fleury, D. Malvy, P. Mercié, I. Pellegrin, P. Morlat, D. Neau, JL. Pellegrin; Drs S. Bouchet, V. Gaborieau, D. Lacoste, S. Tchamgoué, R. ThiébautComposition of the GECSA: Epidemiology and biostatistics: Prs G. Chêne, F. Dabis, R. Thiébaut, Drs M. Bruyand, S. Lawson-Ayayi, L. Wittkop.Clinical and biological hospital units: Bordeaux University Hospital: Pr P. Morlat (Pr F. Bonnet, Drs N. Bernard, M. Hessamfar, D. Lacoste, MA. Vandenhende); Pr M. Dupon (Drs FA. Dauchy, H. Dutronc), Pr M. Longy-Boursier (Pr P. Mercié, Drs P. Duffau, J. Roger Schmeltz), Pr D. Malvy (Drs T. Pistone, MC Receveur), Pr D. Neau (Drs C. Cazanave, A. Ochoa, MO. Vareil), Pr JL. Pellegrin (Pr JF. Viallard, Drs C. Greib, E. Lazaro); Pr H. Fleury (Pr ME. Lafon, Drs S. Reigadas, P. Trimoulet); Pr D. Breilh; Pr M. Molimard (Drs S. Bouchet, K. Titier); Pr JF. Moreau (Dr I. Pellegrin); Drs F. Haramburu, G. Miremont-Salamé. Arcachon Hospital: Dr A. Dupont. Dax Hospital: Dr Y. Gerard (Drs L. Caunègre, K. André). Bayonne Hospital: Dr F. Bonnal (Drs S. Farbos, MC. Gemain). Libourne Hospital: Dr J. Ceccaldi (Dr S. Tchamgoué). Mont-de-Marsan Hospital: Dr S. De Witte (Dr C. Courtault). Pau Hospital: Drs E. Monlun (Dr V. Gaborieau). Périgueux Hospital: Dr P. Lataste (Dr JP. Meraud). Villeneuve-sur-Lot Hospital: Dr I. Chossat.Permanent team: MJ. Blaizeau, M. Bruyand, V. Conte, M. Decoin, J. Delaune, S. Delveaux, F. Diarra, C. D’Ivernois, A. Frosch, S. Geffard, C. Hannapier, S. Lawson-Ayayi, E. Lenaud, O. Leleux, F. Le Marec, J. Leray, I. Louis, G. Palmer, A. Pougetoux, X. Sicard, D. Touchard B. Uwamaliya-Nziyumvira.

AHOD (Australian HIV Observational Database, Australia): Central coordination: M. Law*, K. Petoumenos, H. McManus, S. Wright, C. Bendall (Sydney, New South Wales); Participating physicians (city, state): R. Moore, S. Edwards, J. Hoy, K. Watson, N. Roth, J. Nicholson (Melbourne, Victoria); M Bloch, T. Franic, D. Baker, R. Vale, A. Carr, D. Cooper (Sydney, New South Wales); J. Chuah, M. Ngieng (Gold Coast, Queensland), D. Nolan, J. Skett (Perth, Western Australia).

BASS (Spain): Central coordination: G. Calvo, F. Torres, S. Mateu (Barcelona); Participation physicians (city): P. Domingo, M.A. Sambeat, J. Gatell, E. Del Cacho, J. Cadafalch, M. Fuster (Barcelona); C. Codina, G. Sirera, A. Vaqué (Badalona).

The Brussels St Pierre Cohort (Belgium): Coordination: S. De Wit*, N. Clumeck, M. Delforge, C. Necsoi. Participating physicians: N. Clumeck, S. De Wit*, AF Gennotte, M. Gerard, K. Kabeya, D. Konopnicki, A. Libois, C. Martin, M.C. Payen, P. Semaille, Y. Van Laethem.

CPCRA (USA): Central coordination: J. Neaton, G. Bartsch, W.M. El-Sadr*, E. Krum, G. Thompson, D. Wentworth; Participating physicians (city, state): R. Luskin-Hawk (Chicago, Illinois); E. Telzak (Bronx, New York); W.M. El-Sadr (Harlem, New York); D.I. Abrams (San Francisco, California); D. Cohn (Denver, Colorado); N. Markowitz (Detroit, Michigan); R. Arduino (Houston, Texas); D. Mushatt (New Orleans, Louisiana); G. Friedland (New Haven, Connecticut); G. Perez (Newark, New Jersey); E. Tedaldi (Philadelphia, Pennsylvania); E. Fisher (Richmond, Virginia); F. Gordin (Washington, DC); L.R. Crane (Detroit, Michigan); J. Sampson (Portland, Oregon); J. Baxter (Camden, New Jersey).

EuroSIDA (multinational) Coordinating Centre: J. Lundgren#, O. Kirk*, A. Mocroft, A. Cozzi-Lepri, D. Grint, D. Podlekareva, J. Kjær, L. Peters, J. Tverland, A.H. Fischer, J. Nielsen Participating countries and physicians: Argentina: (M. Losso), C. Elias, Hospital J.M. Ramos Mejia, Buenos Aires. Austria: (N. Vetter), Pulmologisches Zentrum der Stadt Wien, Vienna; R. Zangerle, Medical University Innsbruck, Innsbruck. Belarus: (I. Karpov), A. Vassilenko, Belarus State Medical University, Minsk, V.M. Mitsura, Gomel State Medical University, Gomel; O. Suetnov, Regional AIDS Centre, Svetlogorsk. Belgium: (N. Clumeck), S. De Wit*, M. Delforge, Saint-Pierre Hospital, Brussels; R. Colebunders, Institute of Tropical Medicine, Antwerp; L. Vandekerckhove, University Ziekenhuis Gent, Gent. Bosnia-Herzegovina: (V Hadziosmanovic), Klinicki Centar Univerziteta Sarajevo, Sarajevo. Bulgaria: (K. Kostov), Infectious Diseases Hospital, Sofia. Croatia: (J. Begovac), University Hospital of Infectious Diseases, Zagreb. Czech Republic: (L. Machala), D. Jilich, Faculty Hospital Bulovka, Prague; D. Sedlacek, Charles University Hospital, Plzen. Denmark: (J. Nielsen), G. Kronborg, T. Benfield, M. Larsen, Hvidovre Hospital, Copenhagen; J. Gerstoft, T. Katzenstein, A.-B.E. Hansen, P. Skinhøj, Rigshospitalet, Copenhagen; C. Pedersen, Odense University Hospital, Odense; L. Ostergaard, Skejby Hospital, Aarhus. Estonia: (K. Zilmer), West-Tallinn Central Hospital, Tallinn; Jelena Smidt, Nakkusosakond Siseklinik, Kohtla-Järve. Finland: (M. Ristola), Helsinki University Central Hospital, Helsinki. France: (C. Katlama), Hôpital de la Pitié-Salpétière, Paris; J.-P. Viard, Hôpital Necker-Enfants Malades, Paris; P.-M. Girard, Hospital Saint-Antoine, Paris; J.M. Livrozet, Hôpital Edouard Herriot, Lyon; P. Vanhems, University Claude Bernard, Lyon; C. Pradier, Hôpital de l’Archet, Nice; F. Dabis*, D. Neau, Unité INSERM, Bordeaux. Germany: (J. Rockstroh), Universitäts Klinik Bonn; R. Schmidt, Medizinische Hochschule Hannover; J. van Lunzen, O. Degen, University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit, Hamburg; H.J. Stellbrink, IPM Study Center, Hamburg; M. Bickel, JW Goethe University Hospital, Frankfurt; J. Bogner, Medizinische Poliklinik, Munich; G. Fätkenheuer, Universität Köln, Cologne.

Greece: (J. Kosmidis), P. Gargalianos, G. Xylomenos, J. Perdios, Athens General Hospital; G. Panos, A. Filandras, E. Karabatsaki, 1st IKA Hospital; H Sambatakou, Ippokration Genereal Hospital, Athens. Hungary: (D. Banhegyi), Szent Lásló Hospital, Budapest. Ireland: (F. Mulcahy), St. James's Hospital, Dublin. Israel: (I. Yust), D. Turner, M. Burke, Ichilov Hospital, Tel Aviv; S. Pollack, G. Hassoun, Rambam Medical Center, Haifa; S. Maayan, Hadassah University Hospital, Jerusalem. Italy: (S. Vella), Istituto Superiore di Sanità, Rome; R. Esposito, I. Mazeu, C. Mussini, Università Modena, Modena; C. Arici, Ospedale Riuniti, Bergamo; R. Pristera, Ospedale Generale Regionale, Bolzano; F. Mazzotta, A. Gabbuti, Ospedale S. Maria Annunziata, Firenze; V. Vullo, M. Lichtner, University di Roma la Sapienza, Rome; A. Chirianni, E. Montesarchio, M. Gargiulo, Presidio Ospedaliero A.D. Cotugno, Monaldi Hospital, Napoli; G. Antonucci, A. Testa, P. Narciso, C. Vlassi, M. Zaccarelli, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, Rome; A. Lazzarin, A. Castagna, N. Gianotti, Ospedale San Raffaele, Milan; M. Galli, A. Ridolfo, Osp. L. Sacco, Milan; A. d’Arminio Monforte*, Istituto Di Clinica Malattie Infettive e Tropicale, Milan. Latvia: (B. Rozentale), I. Zeltina, Infectology Centre of Latvia, Riga. Lithuania: (S. Chaplinskas), Lithuanian AIDS Centre, Vilnius. Luxembourg: (R. Hemmer), T. Staub, Centre Hospitalier, Luxembourg. Netherlands: (P. Reiss*), Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam. Norway: (V. Ormaasen), A. Maeland, J Bruun, Ullevål Hospital, Oslo. Poland: (B. Knysz) J. Gasiorowski, Medical University, Wroclaw; A. Horban, E. Bakowska, Centrum Diagnostyki i Terapii AIDS, Warsaw; A. Grzeszczuk, R. Flisiak, Medical University, Bialystok; A. Boron-Kaczmarska, M. Pynka, M. Parczewski, Medical Univesity, Szczecin; M. Beniowski, E. Mularska, Osrodek Diagnostyki i Terapii AIDS, Chorzow; H. Trocha, Medical University, Gdansk; E. Jablonowska, E. Malolepsza, K. Wojcik, Wojewodzki Szpital Specjalistyczny, Lodz. Portugal: (F. Antunes), M. Doroana, L. Caldeira, Hospital Santa Maria, Lisbon; K. Mansinho, Hospital de Egas Moniz, Lisbon; F. Maltez, Hospital Curry Cabral, Lisbon. Romania: (D. Duiculescu), Spitalul de Boli Infectioase si Tropicale: Dr Victor Babes, Bucarest. Russia: (A. Rakhmanova), Medical Academy Botkin Hospital, St Petersburg; N. Zakharova, St Petersburg AIDS Centre, St Peterburg; S. Buzunova, Novgorod Centre for AIDS, Novgorod. Serbia: (D. Jevtovic), The Institute for Infectious and Tropical Diseases, Belgrade. Slovakia: (M. Mokráš), D. Staneková, Dérer Hospital, Bratislava. Slovenia: (J. Tomazic), University Clinical Centre Ljubljana, Ljubljana. Spain: (J. González-Lahoz), V. Soriano, P. Labarga, J. Medrano, Hospital Carlos III, Madrid; S. Moreno, J.M. Rodriguez, Hospital Ramon y Cajal, Madrid; B. Clotet, A. Jou, R. Paredes, C. Tural, J. Puig, I. Bravo, Hospital Germans Trias i Pujol, Badalona; J.M. Gatell, J.M. Miró, Hospital Clinic i Provincial, Barcelona; P. Domingo, M. Gutierrez, G. Mateo, M.A. Sambeat, Hospital Sant Pau, Barcelona. Sweden: (A. Karlsson), Venhaelsan-Sodersjukhuset, Stockholm; L. Flamholc, Malmö University Hospital, Malmö. Switzerland: (B. Ledergerber), R. Weber*, University Hospital, Zürich; P. Francioli, M. Cavassini, Centre Hospitalier Universitaire Vaudois, Lausanne; B. Hirschel, E. Boffi, Hospital Cantonal Universitaire de Geneve, Geneve; H. Furrer, Inselspital Bern, Bern; M. Battegay, L. Elzi, University Hospital Basel. Ukraine: (E. Kravchenko), N. Chentsova, Kiev Centre for AIDS, Kiev; V. Frolov, G. Kutsyna, Luhansk State Medical University; Luhansk; S. Servitskiy, Odessa Region AIDS Center, Odessa; M. Krasnov, Kharkov State Medical University, Kharkov. United Kingdom: (S. Barton), St. Stephen's Clinic, Chelsea and Westminster Hospital, London; A.M. Johnson, D. Mercey, Royal Free and University College London Medical School, London (University College Campus); A. Phillips, M.A. Johnson, A. Mocroft, Royal Free and University College Medical School, London (Royal Free Campus); M. Murphy, Medical College of Saint Bartholomew's Hospital, London; J. Weber, G. Scullard, Imperial College School of Medicine at St. Mary's, London; M. Fisher, Royal Sussex County Hospital, Brighton; C. Leen, Western General Hospital, Edinburgh.

HivBivus (Sweden): Central coordination: L. Morfeldt, G. Thulin, A. Sundström. Participating physicians (city): B. Åkerlund (Huddinge); K. Koppel, A. Karlsson (Stockholm); L. Flamholc, C. Håkangård (Malmö).

The ICONA Foundation (Italy): Board of Directors: M. Moroni (Chair), G. Angarano, A. Antinori, O. Armignacco, A. d’Arminio Monforte*, F. Castelli, R. Cauda, G. Di Perri, M. Galli, R. Iardino, G. Ippolito, A. Lazzarin, C.F. Perno, F. von Schloesser, P. Viale Scientific Secretary: A d’Arminio Monforte*, A. Antinori, A. Castagna, F. Ceccherini-Silberstein, A. Cozzi-Lepri, E. Girardi, S. Lo Caputo, C. Mussini, M. Puoti ICONA Steering Committee: M. Andreoni, A. Ammassari, A. Antinori, A. d’Arminio Monforte, C. Balotta, P. Bonfanti, S. Bonora, M. Borderi, R. Capobianchi, A. Castagna, F. Ceccherini-Silberstein, A. Cingolani, P. Cinque, A. Cozzi-Lepri, A. De Luca, A. Di Biagio, E. Girardi, N. Gianotti, A. Gori, G. Guaraldi, G. Lapadula, M. Lichtner, S. Lo Caputo, G. Madeddu, F. Maggiolo, G. Marchetti, S. Marcotullio, L. Monno, C. Mussini, M. Puoti, E. Quiros Roldan, S. Rusconi Statistical and Monitoring Team: A. Cozzi-Lepri, P. Cicconi, I. Fanti, T. Formenti, L. Galli, P. Lorenzini. Participating Physicians and Centers: A. Giacometti, A. Costantini (Ancona); G. Angarano, L. Monno, C. Santoro (Bari); F. Maggiolo, C. Suardi (Bergamo); P. Viale, E. Vanino, G. Verucchi (Bologna); F. Castelli, E. Quiros Roldan, C. Minardi (Brescia); T. Quirino, C. Abeli (Busto Arsizio); P.E. Manconi, P. Piano (Cagliari); J. Vecchiet, K. Falasca (Chieti); L. Sighinolfi, D. Segala (Ferrara); F. Mazzotta, S. Lo Caputo (Firenze); G. Cassola, G. Viscoli, A. Alessandrini, R. Piscopo, G. Mazzarello (Genova); C. Mastroianni, V. Belvisi (Latina); P. Bonfanti, I. Caramma (Lecco); A.P. Castelli (Macerata); M. Galli, A. Lazzarin, G. Rizzardini, M. Puoti, A. d’Arminio Monforte, A.L. Ridolfo, R. Piolini, A. Castagna, S. Salpietro, L. Carenzi, M.C. Moioli, P. Cicconi, G. Marchetti (Milano); C. Mussini, C. Puzzolante (Modena); A. Gori, G. Lapadula (Monza); N. Abrescia, A. Chirianni, M.G. Guida, M. ONOFRIO (Napoli); F. Baldelli, D. Francisci (Perugia); G. Parruti, T. Ursini (Pescara); G. Magnani, M.A. Ursitti (Reggio Emilia); R. Cauda, M. Andreoni, A. Antinori, V. Vullo, A. Cingolani, A. d’Avino, A. Ammassari, L. Gallo, E. Nicastri, R. Acinapura, M. Capozzi, R. Libertone, G. Tebano (Roma); A. Cattelan (Rovigo); M.S. Mura, G. Madeddu (Sassari); P. Caramello, G. Di Perri, G.C. Orofino, S. Bonora, M. Sciandra (Torino); G. Pellizzer, V. Manfrin (Vicenza).

Nice HIV Cohort (France): Central coordination: C. Pradier*, E. Fontas, C. Caissotti. Participating physicians: P. Dellamonica, E. Bernard, E. Cua, F. De Salvador-Guillouet, J. Durant, S. Ferrando, V. Mondain-Miton, A. Naqvi, I. Perbost, B. Prouvost-Keller, S. Pillet, P. Pugliese, V. Rahelinirina, P.M. Roger. Clinical research assistant: K. Dollet

SHCS (Swiss HIV Cohort Study, Switzerland): V. Aubert, J. Barth, M. Battegay, E. Bernasconi, J Böni, HC. Bucher, C. Burton-Jeangros, A. Calmy, M. Cavassini, M. Egger, L. Elzi, J. Fehr, J. Fellay, H. Furrer (Chairman of the Clinical and Laboratory Committee), CA. Fux, M. Gorgievski, H. Günthard (President of the SHCS), D. Haerry (deputy of ‘Positive Council’), B. Hasse, HH. Hirsch, I Hösli, C. Kahlert, L. Kaiser, O. Keiser, T. Klimkait, H. Kovari, B. Ledergerber, G. Martinetti, B. Martinez de Tejada, K. Metzner, N. Müller, D. Nadal, G. Pantaleo, A. Rauch (Chairman of the Scientific Board), A. Regenass, M. Rickenbach (Head of Data Center), C. Rudin (Chairman of the Mother & Child Substudy), P. Schmid, D. Schultze, F. Schöni-Affolter, J. Schüpbach, R. Speck, P. Taffé, P. Tarr, A. Telenti, A. Trkola, P. Vernazza, R. Weber*, S. Yerly.

Funding This work was supported by the Highly Active Antiretroviral Therapy Oversight Committee (HAART-OC), a collaborative committee with representation from academic institutions, the European Agency for the Evaluation of Medicinal Products, the United States Food and Drug Administration, the patient community, and all pharmaceutical companies with licensed anti-HIV drugs in the European Union: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Viiv Healthcare, Merck, Pfizer, F. Hoffman-LaRoche and Janssen Pharmaceuticals.

Supported by a grant [grant number CURE/97-46486] from the Health Insurance Fund Council, Amstelveen, the Netherlands, to the AIDS Therapy Evaluation Project Netherlands (ATHENA); by a grant from the Agence Nationale de Recherches sur le SIDA [grant number Action Coordonnée no. 7, Cohortes], to the Aquitaine Cohort; The Australian HIV Observational Database (AHOD) is funded as part of the Asia Pacific HIV Observational Database, a program of The Foundation for AIDS Research, amfAR, and is supported in part by a grant from the U.S. National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID) [grant number U01-AI069907] and by unconditional grants from Merck Sharp & Dohme; Gilead Sciences; Bristol-Myers Squibb; Boehringer Ingelheim Roche; Pfizer; GlaxoSmithKline; Janssen Pharmaceuticals. The Kirby Institute is funded by The Australian Government Department of Health and Ageing, and is affiliated with the Faculty of Medicine, The University of New South Wales. By grants from the Fondo de Investigación Sanitaria [grant number FIS 99/0887] and Fundación para la Investigación y la Prevención del SIDA en Espanã [grant number FIPSE 3171/00], to the Barcelona Antiretroviral Surveillance Study (BASS); by the National Institute of Allergy and Infectious Diseases, National Institutes of Health [grants number 5U01AI042170-10, 5U01AI046362-03], to the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA); by grants from the BIOMED 1 [grant number CT94-1637] and BIOMED 2 [grant number CT97-2713] programs and the fifth framework program [grant number QLK2-2000-00773] of the European Commission and grants from Bristol-Myers Squibb, GlaxoSmithKline, Boehringer Ingelheim and Roche, to the EuroSIDA study; by unrestricted educational grants of AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Pfizer, Janssen Pharmaceuticals to the Italian Cohort Naive to Antiretrovirals (The ICONA Foundation); and by a grant from the Swiss National Science Foundation, to the Swiss HIV Cohort Study (SHCS). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of any of the institutions mentioned above.

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Conflicts of interest

L.R., J.D.L., W.E.S. and M.R. no conflicts of interest. A.M. has received consultancy fees/honoraria/speaker fees from BMS, Pfizer, Merck, BI, and Gilead Sciences. O.K. had prior/present board membership at ViiV Healthcare, Gilead Sciences and Merck, received payment for lectures and/or for development of educational presentations from Abbott, Gilead Sciences and Tibotec. Travel/accommodations/meeting expenses from Abbott, BMS, Gilead Sciences, Merck and ViiV Healthcare. P.R. has served as a scientific advisor to Bristol-Myers Squibb, Gilead Sciences, Grupo Ferrer, GlaxoSmithKline, Janssen Pharmaceuticals, Merck & Co, Inc, and ViiV Healthcare. He has served on data and safety monitoring boards and endpoint adjudication committees for Janssen Pharmaceuticals and his institution has received honoraria for speaking engagements at scientific conferences from Bristol-Myers Squibb, Gilead Sciences, Inc, GlaxoSmithKline. He has received research support from Gilead Sciences, ViiV Healthcare, Merck & Co, Inc, Janssen Pharmaceuticals, Bristol-Myers Squibb, Abbott, and Boehringer Ingelheim Pharmaceuticals. C.A.F. is an advisory board member for Gilead Sciences and MSD, has pending grants from Gilead Sciences and Abbott and received payment for lectures by Gilead HIV and the body. P.M. is board member at ViiV Healthcare, MSD, Gilead Sciences and Boehringer Ingelheim Pharmaceuticals and had expenses paid for travel/accommodation/meetings by BMS, ViiV Healthcare, Abbott and MSD. O.M. has received honoraria speaker from Abbott and Gilead Sciences, is a board member for Roche and had expenses paid for travel/accommodation/meetings by Roche and Baxter companies. C.S. has a pending grant from Bristol-Myers Squibb and received payment for development of educational presentations by Gilead Sciences. M.L. is has received research grants from Boehringer Ingelheim, Bristol Myer Squibb, Gilead, GlaxoSmithKline, Janssen-Cilag Pty Ltd, Merck Sharp & Dohme, Pfizer and Roche.

This work was presented in part at CROI 2013, Atlanta, Georgia, USA, abstract # R-140.

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advanced chronic kidney disease; adverse events; antiretroviral agents; end-stage renal disease; HIV; nephrotoxicity; tenofovir

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