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Recent abacavir use and incident cardiovascular disease in contemporary treated people living with HIV (PLWH) within the RESPOND cohort consortium
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Recent Abacavir Boosts Cardio Disease Risk 40% in 29,340-Person Analysis
18th European AIDS Conference, EACS 2021, October 27-30, 2021, London
Mark Mascolini
Analysis of the European/Australian RESPOND cohort linked recent abacavir to a 40% higher risk of new cardiovascular disease [1]. This association did not change after statistical adjustment for kidney function and other variables.
D:A:D study investigators first reported higher risk of myocardial infarction (MI) with abacavir [2], and further research implicated increased platelet reactivity as a possible mechanism [3]. Although other studies have been less consistent in linking abacavir to cardiovascular disease (CVD), research so far led antiretroviral guideline writers to view abacavir use with some caution.
This new study set out to see whether abacavir remained associated with CVD in the current treatment era in the RESPOND group, a collaboration of 17 cohorts in Europe and Australia [4]. This analysis included RESPOND members at least 18 years old followed from cohort enrollment or January 1, 2012, whichever came later. Follow-up continued to the first CVD event, December 31, 2019, or the last cohort follow-up date, whichever came first. The researchers defined CVD as a composite endpoint including MI, stroke, and invasive cardiovascular procedures. Recent abacavir use meant current use or use within the past 6 months.
Statisticians used negative binomial regression to explore potential associations between recent abacavir use and CVD risk adjusted for age, sex, ethnicity, region, body mass index, HIV transmission risk group, CD4 count, hypertension, diabetes, AIDS, CVD, CKD, and abnormal lipids at baseline. Time-updated variables were calendar year, smoking status, integrase inhibitor use, cumulative use of boosted lopinavir and darunavir, indinavir, didanosine, and stavudine. Logistic regression assessed the odds of starting abacavir by estimated D:A:D 5-year CVD and 5-year CKD risk score strata.
The study group included 29,340 people with a median age of 44 years (interquartile range [IQR] 36 to 51) and a median CD4 count of 524 (IQR 357 to 715). Most participants were men (74%) and white (70%), and sex between men was the most frequent HIV risk (45%). Major baseline CVD risk factors were abnormal lipids in 61%, current smoking in 28%, hypertension in 19%, and diabetes in 4%. One third of participants, 34%, currently took abacavir, of whom 32% also took a boosted protease inhibitor.
Through a median 6.16 years (160,252 person-years) of follow-up, cohort members had 748 CVD events, including 299 MIs, 228 strokes, and 221 invasive cardiovascular procedures. CVD incidence came to 4.7 per 1000 person-years (95% confidence interval [CI] 4.3 to 5.0).
People with higher D:A:D cardiovascular risk scores were less likely to start abacavir during the study period. Compared with people who had low cardiovascular risk, adjusted odds of starting abacavir were 0.80 in people with moderate cardiovascular risk (P < 0.001), 0.75 in those with high risk (P < 0.001), and 0.71 in those with very high risk (P < 0.001). People with a moderate D:A:D CKD risk score had lower adjusted odds of starting abacavir than people with low CKD risk (0.83, P < 0.001), while people with a high CKD risk score had higher adjusted odds of starting abacavir (1.12, P < 0.001).
The primary adjusted regression analysis linked recent abacavir use (compared with no abacavir) to a 40% higher risk of CVD (incidence rate ratio [IRR] 1.40, 95% CI 1.20 to 1.64). This independently higher risk of CVD held true when the analysis excluded stroke and invasive cardiovascular procedures (IRR 1.64, 95% CI 1.29 to 2.07), excluded CVD as a baseline variable (IRR 1.50, 95% CI 1.27 to 1.76), adjusted only for D:A:D 5-year CVD risk score (IRR 1.48, 95% CI 1.27 to 1.72), and adjusted only for D:A:D 5-year CKD risk score (IRR 1.49, 95% CI 1.28 to 1.74). An interaction analysis yielded no evidence that the higher CVD risk with recent abacavir differed according to CVD or CKD risk score stratum.
References
1. Jaschinski NJ, Greenberg L, Beesgaard B, et al. Recent abacavir use and incident cardiovascular disease in contemporary treated people living with HIV (PLWH) within the RESPOND cohort consortium. 18th European AIDS Conference, EACS 2021, October 27-30, 2021, London. Abstract BPD1/3.
2. D:A:D Study Group, Sabin CA, Worm SW, Weber R, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet. 2008;371:1417-1426. doi: 10.1016/S0140-6736(08)60423-7.
3. Baum PD, Sullam PM, Stoddart CA, McCune JM. Abacavir increases platelet reactivity via competitive inhibition of soluble guanylyl cyclase. AIDS. 2011;25:2243-2248. doi: 10.1097/QAD.0b013e32834d3cc3.
4. The Respond Study Group. How to RESPOND to modern challenges for people living with HIV: a profile for a new cohort consortium. Microorganisms. 2020;8:1164. doi: 10.3390/microorganisms8081164.
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