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Observational Study
. 2017 Nov 7;14(11):e1002424.
doi: 10.1371/journal.pmed.1002424. eCollection 2017 Nov.

Cardiovascular disease (CVD) and chronic kidney disease (CKD) event rates in HIV-positive persons at high predicted CVD and CKD risk: A prospective analysis of the D:A:D observational study

Mark A Boyd  1   2 , Amanda Mocroft  3 , Lene Ryom  4 , Antonella d'Arminio Monforte  5 , Caroline Sabin  3 , Wafaa M El-Sadr  6 , Camilla Ingrid Hatleberg  4 , Stephane De Wit  7 , Rainer Weber  8 , Eric Fontas  9 , Andrew Phillips  3 , Fabrice Bonnet  10   11 , Peter Reiss  12   13   14 , Jens Lundgren  4 , Matthew Law  1
Affiliations
Observational Study

Cardiovascular disease (CVD) and chronic kidney disease (CKD) event rates in HIV-positive persons at high predicted CVD and CKD risk: A prospective analysis of the D:A:D observational study

Mark A Boyd et al. PLoS Med. .

Abstract

Background: The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study has developed predictive risk scores for cardiovascular disease (CVD) and chronic kidney disease (CKD, defined as confirmed estimated glomerular filtration rate [eGFR] ≤ 60 ml/min/1.73 m2) events in HIV-positive people. We hypothesized that participants in D:A:D at high (>5%) predicted risk for both CVD and CKD would be at even greater risk for CVD and CKD events.

Methods and findings: We included all participants with complete risk factor (covariate) data, baseline eGFR > 60 ml/min/1.73 m2, and a confirmed (>3 months apart) eGFR < 60 ml/min/1.73 m2 thereafter to calculate CVD and CKD risk scores. We calculated CVD and CKD event rates by predicted 5-year CVD and CKD risk groups (≤1%, >1%-5%, >5%) and fitted Poisson models to assess whether CVD and CKD risk group effects were multiplicative. A total of 27,215 participants contributed 202,034 person-years of follow-up: 74% male, median (IQR) age 42 (36, 49) years, median (IQR) baseline year of follow-up 2005 (2004, 2008). D:A:D risk equations predicted 3,560 (13.1%) participants at high CVD risk, 4,996 (18.4%) participants at high CKD risk, and 1,585 (5.8%) participants at both high CKD and high CVD risk. CVD and CKD event rates by predicted risk group were multiplicative. Participants at high CVD risk had a 5.63-fold (95% CI 4.47, 7.09, p < 0.001) increase in CKD events compared to those at low risk; participants at high CKD risk had a 1.31-fold (95% CI 1.09, 1.56, p = 0.005) increase in CVD events compared to those at low risk. Participants' CVD and CKD risk groups had multiplicative predictive effects, with no evidence of an interaction (p = 0.329 and p = 0.291 for CKD and CVD, respectively). The main study limitation is the difference in the ascertainment of the clinically defined CVD endpoints and the laboratory-defined CKD endpoints.

Conclusions: We found that people at high predicted risk for both CVD and CKD have substantially greater risks for both CVD and CKD events compared with those at low predicted risk for both outcomes, and compared to those at high predicted risk for only CVD or CKD events. This suggests that CVD and CKD risk in HIV-positive persons should be assessed together. The results further encourage clinicians to prioritise addressing modifiable risks for CVD and CKD in HIV-positive people.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: MB has received research grants, paid to his institution from Merck Sharp & Dohme and Gilead Sciences. MB has also received honoraria for participation on HIV advisory boards and preparation and delivery of educational materials from Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme and ViiV Healthcare. AM has received honoraria, travel support, speaker fees and consultancy fees from ViiV, BMS, BI, Gilead, and Wragge LLC; AP received speaker fees for a 2015 conference for Gilead Sciences; ML has received unrestricted research grants, paid to his institution, from Boehringer Ingelhiem, Gilead Sciences, Merck Sharp & Dohme, Bristol-Myers Squibb, Janssen-Cilag, ViiV HealthCare; ML has also received consultancy and presentation fees from Gilead Sciences, and DSMB sitting fees from Sirtex Pty Ltd; PR through his institution has received independent scientific grant support from Gilead Sciences, Janssen Pharmaceuticals Inc, Merck & Co, Bristol-Myers Squibb and ViiV Healthcare; PR has served on a scientific advisory board for Gilead Sciences and ViiV Healthcare, as well as on a data safety monitoring committee for Janssen Pharmaceuticals Inc, and has chaired a scientific symposium by ViiV and received remuneration; CS's institution has received a grant from the D:A:D Oversight Committee for the analysis and co-ordination of the D:A:D Study; CS has also received personal fees from Gilead Sciences, ViiV Healthcare and Janssen-Cilag for the membership of Data Safety and Monitoring Boards, Advisory Boards, Speaker Panels and for the preparation of educational materials.

Figures

Fig 1
Fig 1. CKD event rates according to CKD and CVD risk.
CKD, chronic kidney disease; CVD, cardiovascular disease; pyrs, person-years.
Fig 2
Fig 2. CVD event rates according to CKD and CVD risk.
CKD, chronic kidney disease; CVD, cardiovascular disease; pyrs, person-years.
See this image and copyright information in PMC

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