Risk of cardiovascular disease associated with exposure to abacavir among individuals with HIV: A systematic review and meta-analyses of results from 17 epidemiologic studies

Dorjee, Kunchok; Choden, Tsering; Baxi, Sanjiv M.; Steinmaus, Craig; Reingold, Arthur

doi:10.1016/j.ijantimicag.2018.07.010

Cited by 44 publications

(35 citation statements)

References 64 publications

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“…The risk of AMI associated with ART use was robustly reported in the Data collection on adverse events of ARV Drugs (D.A.D) study (26) in which duration of ART was associated with an adjusted relative risk of AMI of 1.26 [1.12–1.41] per year. Specific drugs, or classes of drug, have also been associated with CV events; recent, but not cumulative use, of abacavir (27) and continued use of protease inhibitors (26, 28) including some recently-introduced combinations (29). The study by Ryom and colleagues using data from the D:A:D cohort, showed that cumulative use of the boosted protease inhibitor combination darunavir/ritonavir was associated with a 60% increase in baseline risk of CVD (using a composite endpoint that included AMI and stroke, and also sudden cardiac deaths and invasive cardiovascular procedures) over 5 years of use.…”

Section: Why Is Cvd Risk Elevated In Virologically Suppressed Hiv-posmentioning

confidence: 99%

How Monocytes Contribute to Increased Risk of Atherosclerosis in Virologically-Suppressed HIV-Positive Individuals Receiving Combination Antiretroviral Therapy

et al. 2019

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Combination antiretroviral therapy (ART) is effective at suppressing HIV viremia to achieve persistently undetectable levels in peripheral blood in the majority of individuals with access and ability to maintain adherence to treatment. However, evidence suggests that ART is less effective at eliminating HIV-associated inflammation and innate immune activation. To the extent that residual inflammation and immune activation persist, virologically suppressed people living with HIV (PLWH) may have increased risk of inflammatory co-morbidities, and adjunctive therapies may need to be considered to reduce HIV-related inflammation and fully restore the health of virologically suppressed HIV+ individuals. Cardiovascular disease (CVD) is the single leading cause of death in the developed world and is becoming more important in PLWH with access to ART. Arterial disease due to atherosclerosis, leading to acute myocardial infarction (AMI) and stroke, is a major component of CVD. Atherosclerosis is an inflammatory disease, and epidemiological comparisons of atherosclerosis and AMI show a higher prevalence and suggest a greater risk in PLWH compared to the general population. The reasons for greater prevalence of CVD in PLWH can be broadly grouped into four categories: (a) the higher prevalence of traditional risk factors e.g., smoking and hypertension (b) dyslipidemia (also a traditional risk factor) caused by off-target effects of ART drugs (c) HIV-related inflammation and immune activation and (d) other undefined HIV-related factors. Management strategies aimed at reducing the impact of traditional risk factors in PLWH are similar to those for the general population and their effectiveness is currently being evaluated. Together with improvements in ART regimens and guidelines for treatment, and a greater awareness of its impact on CVD, the HIV-related risk of AMI and stroke is decreasing but remains elevated compared to the general community. Monocytes are key effector cells which initiate the formation of atherosclerotic plaques by migrating into the intima of coronary arteries and accumulating as foam cells full of lipid droplets. This review considers the specific role of monocytes as effector cells in atherosclerosis which progresses to AMI and stroke, and explores mechanisms by which HIV may promote an atherogenic phenotype and function independent of traditional risk factors. Altered monocyte function may represent a distinct HIV-related factor which increases risk of CVD in PLWH.

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Section: Why Is Cvd Risk Elevated In Virologically Suppressed Hiv-posmentioning

confidence: 99%

How Monocytes Contribute to Increased Risk of Atherosclerosis in Virologically-Suppressed HIV-Positive Individuals Receiving Combination Antiretroviral Therapy

et al. 2019

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“…Abacavir should not be used in HLA-B Ã 5701 positive patients or in patients co-infected with hepatitis B. There are also data indicating slightly increased risk of cardiovascular disease with abacavir therapy [25,26]. These data are, however, contradicted by investigations unable to demonstrate an increased risk of cardiovascular disease [27].…”

Section: Rationale For Recommendationmentioning

confidence: 99%

Antiretroviral treatment for HIV infection: Swedish recommendations 2019

Eriksen

Carlander

Albert

et al. 2020

Infectious Diseases

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The Swedish Reference Group for Antiviral Therapy (RAV) published recommendations for the treatment of HIV infection in this journal most recently in 2017. An expert group under the guidance of RAV here provides updated recommendations. The most important updates in the present guidelines are the following: (a) The risk of HIV transmission through condomless sex from individuals with fully suppressed HIV viral load is effectively zero. (b) Pre-exposure prophylaxis (PrEP) is recommended for groups with a high risk of HIV infection. (c) Since the last update, two new substances have been registered: bictegravir and doravirine. (d) Dual treatment may be an alternative in selected patients, using lamivudine þ dolutegravir or lamivudine þ boosted darunavir/atazanavir. As with previous publications, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine. This document does not cover treatment of opportunistic infections and tumours.

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“…13 Evidence shows that chronic inflammation associated with HIV infection and CV side effects of some protease inhibitors (PIs) and abacavir are the main specific risk factors, in addition to the traditional risk factors such as smoking, obesity, dyslipidemia and diabetes. 13,14 High blood pressure Of all the CV disorders, hypertension is the most prevalent CV condition among individuals with HIV infection. 15,16 There are multiple contributing mechanisms, from chronic inflammation and endothelial dysfunction to renin-angiotensin-aldosterone system activation and lipodystrophy.…”

Section: Consensus Statement Cardio-metabolic Diseasementioning

confidence: 99%

Consensus statement on the assessment of comorbidities in people living with HIV in Romania

Streinu‐Cercel¹,

Săndulescu²,

Poiană

et al. 2019

Germs

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Introduction The life expectancy of HIV-infected patients has been increased by highly effective therapies. People living with HIV (PLWH) in Romania are exposed to age-related comorbidities occurring earlier than in uninfected individuals. Multidisciplinary care is required to maintain the general health and quality of life in these patients. Currently, the communication among different specialties needs to be enhanced and formalized. Methods A panel consisting of 8 Romanian experts in infectious diseases, cardio-metabolic, bone, and kidney diseases and psychology met in May 2019 in Bucharest Romania to discuss the need to evaluate and monitor the most prevalent comorbidities in PLWH. The meeting resulted in practical guidance on the management of several non-infectious associated diseases. The algorithms were endorsed by the Society for Infectious Diseases and HIV/AIDS, Romania. Results The consensus statement offers practical guidance on how to assess and monitor associated diseases in adult PLWH. The recommendations are grouped for each cluster of comorbidities and are based on international guidelines and clinical experience, including landmarks for referral of PLWH to cardiology, endocrinology, nephrology specialist or clinical psychologist for additional investigations and adequate treatment. Specific indications for diagnosis or treatment were beyond the scope of this consensus. Conclusions Screening for associated diseases and adequate management are required to maintain the overall health status of PLWH. When implemented in clinical practice, the recommended algorithms should be used in addition to diagnosis and treatment guidelines and protocols. The infectious diseases specialist plays a key role in coordinating the overall treatment strategy and working within the multidisciplinary team.

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Risk of cardiovascular disease associated with exposure to abacavir among individuals with HIV: A systematic review and meta-analyses of results from 17 epidemiologic studies

Abstract: Our findings suggest an increased risk of CVD from recent abacavir exposure. The risk remained elevated after adjusting for potential confounders. Further investigations are needed to understand CVD risk from cumulative exposure.

Cited by 44 publications

References 64 publications

How Monocytes Contribute to Increased Risk of Atherosclerosis in Virologically-Suppressed HIV-Positive Individuals Receiving Combination Antiretroviral Therapy

How Monocytes Contribute to Increased Risk of Atherosclerosis in Virologically-Suppressed HIV-Positive Individuals Receiving Combination Antiretroviral Therapy

Antiretroviral treatment for HIV infection: Swedish recommendations 2019

Consensus statement on the assessment of comorbidities in people living with HIV in Romania

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