CROI 2017 Abstract e-Book

Abstract eBook

Oral Abstracts

Methods: D:A:D study participants under follow-up (FU) after 01.01.2009 were followed to the earliest of CVD, last visit plus 6 months or 01.02.2016. CVD was defined as centrally validated myocardial infarction, stroke, sudden cardiac death or invasive cardiovascular procedures (coronary bypass, coronary angioplasty and carotid endarterectomy). Poisson regression models assessed associations between CVD and use of two contemporarily and frequently used PIs atazanavir (ATV/r) and darunavir (DRV/r).

Results: Of 35,711 included persons, 1,157 developed CVD (IR 5.3/1000 PYFU [95%CI 5.0-5.6]) during 7.0 (IQR 6.3-7.1) years median FU. The crude CVD IR increased gradually from 4.91/1000 PYFU [4.59-5.23] in those never exposed to DRV/r to 13.67/1000 PYFU [8.51-18.82] in those exposed >6 years, while the changes with ATV/r were less pronounced (from 5.03 [4.69-5.37] to 6.68/1000 PYFU [5.02-8.35]), (figure). After adjustment for factors not considered on the causal pathway between PI/r use and CVD, cumulative exposure to DRV/r, but not ATV/r, was associated with excess CVD risk (IRR 1.59 [1.33-1.91] and 1.03 [0.90-1.18]/5 years respectively). Additional adjustment for time-updated dyslipidemia, and other factors potentially on the causal pathway to CVD, did not affect the association (DRV/r 1.53 [1.28-1.84] and ATV/r 1.01 [0.88-1.16]/5 years). The associations remained consistent for; myocardial infarction and stroke separately; after adjustment for bilirubin levels (associated with ATV/r use and potentially protective of CVD); when stratifying for whether DRV/r was used as the first ever PI/r containing regimen or not (p=0.29 for interaction); whether DRV/r was used with a non-nucleoside reverse transcriptase inhibitor or not (p=0.43 for interaction); and in those at high vs. low estimated 5 year CVD risk (p=0.12 for interaction).

Oral Abstracts

Conclusion: In this large heterogeneous cohort of HIV-positive persons, cumulative use of DRV/r, but not ATV/r, was independently associated with a small, but gradually increasing CVD risk. Causal inference is limited by the observational nature of our data, but the findings call for further investigations into possible underlying mechanisms. 129 CARDIOVASCULAR PREVENTION POLICY IN HIV: RECOMMENDATIONS FROM A MODELING STUDY Rosan van Zoest 1 , Mikaela Smit 2 , Brooke Nichols 3 , Ilonca Vaartjes 4 , Colette Smit 5 , Marc van der Valk 6 , Ferdinand Wit 5 , Timothy B. Hallett 2 , Peter Reiss 5 , for the Netherlands ATHENA Observational HIV Cohort 1 Amsterdam Inst for Global Hlth and Development and Academic Med Cntr, Amsterdam, Netherlands, 2 Imperial Coll London, London, UK, 3 Erasmus Univ Med Cntr, Rotterdam, Netherlands, 4 Univ Med Cntr Utrecht, Utrecht, Netherlands, 5 Stichting HIV Monitoring, Amsterdam, Netherlands, 6 Academic Med Cntr, Amsterdam, Netherlands Background: Cardiovascular disease (CVD) is expected to contribute the largest non-communicable disease burden amongst HIV-positive people over the coming decades. We modeled the impact of different CVD prevention interventions in Dutch HIV-positive patients and determined which is best use of resources. Methods: An individual-based model of CVD in ageing Dutch HIV-positive patients was constructed using 1996-2010 data from 8,791 patients on combination antiretroviral therapy (cART) from the national ATHENA cohort. The model follows patients in care, including new patients, as they age, develop (risk factors for) CVD (by incorporating the D:A:D CVD risk equation) and start CVD medication, and was validated on 2010-2015 data. Four interventions were evaluated between 2017 and 2030, assuming 100% and 50% implementation success: 1) reducing the number of late presenters (i.e. CD4 count <500 cells/mm³); 2) use of cART with no known increased CVD risk; 3) a smoking cessation program; 4) intensified monitoring and drug treatment of hypertension and dyslipidemia. Interventions were evaluated in all patients and in moderate to high CVD risk patients only (HR, 5-year CVD risk ≥5%). Economic evaluations were performed assuming 50% implementation success, accounting for all costs related to HIV/CVD treatment. Results: The model predicts that CVD incidence will increase by 50% between 2015 and 2030 and that intensified monitoring and treatment of hypertension and dyslipidemia will have the greatest impact on averting CVD events, followed by a smoking cessation program (Figure). Economic evaluations identified three interventions with the potential to be cost-effective: smoking cessation in HR patients, decreasing the number of late presenters in all patients, and intensified monitoring and treatment of hypertension and dyslipidemia in HR patients. The latter is most likely to be the best use of resources and could be cost-effective or even cost-saving. Conclusion: Our study is the first to provide evidence to guide policy makers concerning which high-impact CVD prevention interventions to prioritize as part of HIV care, recommending intensified monitoring and successful treatment of hypertension and dyslipidemia in moderate to high CVD risk patients as the best use of resources by focusing on addressing the gap between current clinical care and standard guidelines. Quantifying additional public health benefits, beyond CVD, of all four interventions, is likely to provide further evidence for policy development.

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CROI 2017