Cardiovascular risks associated with protease inhibitors for the treatment of HIV

Abstract

Introduction: Cumulative use of some first-generation protease inhibitors has been associated with higher rates of dyslipidemia and increased risk of cardiovascular disease. The protease inhibitors most commonly in use are atazanavir and darunavir, which have fewer detrimental lipid effects and greater tolerability. This paper aims to review the evidence of a potential association of these contemporary protease inhibitors with the risk of ischemic CVD and atherosclerotic markers. Areas covered:We searched for publications of randomized trials and observational studies on PubMed from 1st January 2000 onwards, using search terms including: protease inhibitors; darunavir; atazanavir; cardiovascular disease; cardiovascular events; dyslipidemia; mortality; carotid intima media thickness; arterial elasticity; arterial stiffness and drug discontinuation.Ongoing studies registered on clinicaltrials.gov as well as conference abstracts from major HIV conferences from 2015-2020 were also searched.Expert opinion: Atazanavir and darunavir are no longer part of first-line HIV treatment, but continue to be recommended as alternative first line, second-and third-line regimens, as part of two drug regimens, and darunavir is used as salvage therapy. Although these drugs will likely remain in use globally for several years to come, baseline CVD risk should be considered when considering their use, especially as the population with HIV ages. Article highlights box:• History and biological properties of PIs • Association of contemporary PIs with surrogate markers for atherosclerotic CVD • Contemporary PIs and association with clinical CVD • PI boosters and risk of CVD • Possible biological mechanisms for contemporary PIs and association with CVD • Clinical approach to the use of contemporary PIs

Evaluation of Lipid Profile and Intima Media Thickness in Antiretroviral-Experienced HIV-Infected Patients Treated with Protease Inhibitor-Based Regimens versus Protease Inhibitor-Sparing Regimens

“…These data may suggest that CVD is a risk factor related to the class of PI and to specific previous drugs. In fact, in a recent review of 2021, Hateleberg et al concluded that although PIs will likely remain in use globally for several years to come, baseline CVD risk should be considered when selecting their use, especially as the population with HIV ages [24]. This is the reason why more metabolic-friendly treatment regimens have been developed in recent years.…”

Epigenetics-Associated Risk Reduction of Hematologic Neoplasms in a Nationwide Cohort Study: The Chemopreventive and Therapeutic Efficacy of Hydralazine

“…Nelfinavir is an antiviral drug, acting as protease inhibitor and repurposed for HNs by its activity to inhibit the Akt/PKB signaling pathway or to activate ER stress (47). As repurposing nelfinavir for HNs, subjects may suffer from adverse effects caused by the activity of protease inhibitor such as cardiovascular risks (48). In summary, whether a The 1 st endpoint in the cohort was defined as the date to stop follow-up when the diagnosis of any HN was made for a subject, while the 2 nd endpoint was defined as the end of tracking when follow-up of all the subjects was stopped.…”

Diseases of the Cardiovascular System in HIV-infected Patients: Risk Factors and Mechanisms of Progression

“…АРТ вызывает кардиометаболическую токсичность, либо индуцируя новые сердечно-сосудистые факторы риска (такие как дислипидемия, резистентность к инсулину и увеличение веса), либо усугубляя существующие [32]. Ингибиторы протеазы первого поколения и абакавир связаны с бóльшим количеством побочных эффектов со стороны сердечно-сосудистой системы, чем новые препараты [33,34]. Исследование SMART показало, что нарушение континуума АРТ было связано с повышенным риском острого инфаркта миокарда (ИМ), вероятно, из-за воспаления, вызванного рикошетной виремией [33].…”