Risk of Cardiovascular Disease from Antiretroviral Therapy for HIV: A Systematic Review

Abstract

BackgroundRecent studies suggest certain antiretroviral therapy (ART) drugs are associated with increases in cardiovascular disease.PurposeWe performed a systematic review and meta-analysis to summarize the available evidence, with the goal of elucidating whether specific ART drugs are associated with an increased risk of myocardial infarction (MI).Data SourcesWe searched Medline, Web of Science, the Cochrane Library, and abstract archives from the Conference on Retroviruses and Opportunistic Infections and International AIDS Society up to June 2011 to identify published articles and abstracts.Study SelectionEligible studies were comparative and included MI, strokes, or other cardiovascular events as outcomes.Data ExtractionEligibility screening, data extraction, and quality assessment were performed independently by two investigators.Data SynthesisRandom effects methods and Fisher’s combined probability test were used to summarize evidence.FindingsTwenty-seven studies met inclusion criteria, with 8 contributing to a formal meta-analysis. Findings based on two observational studies indicated an increase in risk of MI for patients recently exposed (usually defined as within last 6 months) to abacavir (RR 1.92, 95% CI 1.51–2.42) and protease inhibitors (PI) (RR 2.13, 95% CI 1.06–4.28). Our analysis also suggested an increased risk associated with each additional year of exposure to indinavir (RR 1.11, 95% CI 1.05–1.17) and lopinavir (RR 1.22, 95% CI 1.01–1.47). Our findings of increased cardiovascular risk from abacavir and PIs were in contrast to four published meta-analyses based on secondary analyses of randomized controlled trials, which found no increased risk from cardiovascular disease.ConclusionAlthough observational studies implicated specific drugs, the evidence is mixed. Further, meta-analyses of randomized trials did not find increased risk from abacavir and PIs. Our findings that implicate specific ARTs in the observational setting provide sufficient evidence to warrant further investigation of this relationship in studies designed for that purpose.

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

“…A number of studies have documented increased rates of cardiovascular and cerebrovascular disease in HIV‐infected adults, which appear to be multifactorial and relate both to HIV disease itself and ART, with the greater risk associated with PIs and ABC 104, 105. Several mechanisms have been postulated, including metabolic and lipid derangement (especially related to PI), insulin resistance, direct vascular injury and increased inflammation 106.…”

Role of endoplasmic reticulum stress in drug‐induced toxicity

“…Some PIs such as indinavir, lopinavir, and ritonavir are suspected to increase the risk of cardiovascular diseases including myocardial infarction (Bavinger et al. 2013; Margolis et al. 2014).…”

Enfermedad cardiovascular y metabólica en pacientes infectados por el virus de la inmunodeficiencia humana

“…reportaron una incidencia de eventos coronarios de 5,5 por 1 000 pacientes-año en pacientes que recibían tratamiento, lo cual fue mayor que en el grupo control 45 . Se ha sugerido que el uso de Inhibidores de Proteasa (IP) y el uso reciente o actual de Abacavir puede aumentar hasta dos veces el riesgo de infarto por un aumento de la dislipidemia, la resistencia a la insulina, la activación plaquetaria, niveles aumentados de péptido C, la lipodistrofia y la disfunción endotelial 44,46 .…”