Recommendations for Managing Drug–Drug Interactions with Statins and HIV Medications

Lamprecht, Donald G.; Page, Robert L.; Saseen, Joseph J.

doi:10.1007/s40256-017-0222-7

Cited by 37 publications

(21 citation statements)

References 46 publications

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“…Treatment for hypertension can interact with ARVs that may deter concomitant prescriptions. 21 However, all 106 persons living with HIV/AIDS who lacked ARVs had Part D drug coverage. We also found in subanalyses that all 106 had other drugs paid for during the first 100 days of their long NH stay, just no ARVs.…”

Section: Discussionmentioning

confidence: 99%

Economic Barriers to Antiretroviral Therapy in Nursing Homes

Olivieri‐Mui

Koethe

Briesacher

2019

J American Geriatrics Society

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OBJECTIVES Our aim was to clarify if persons living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) have adequate economic access to antiretroviral therapy (ART) when admitted to nursing homes (NHs). Medicare Part A pays NHs a bundled skilled nursing rate that includes prescription drugs for up to 100 days, after which individuals are responsible for the costs. DESIGN A cross‐sectional study. SETTING NHs. PARTICIPANTS A total of 694 newly admitted long‐stay (>100 d) NH residents with HIV. MEASUREMENTS We used Minimum Dataset v.3.0, pharmacy dispensing data, NH provider surveys, and Medicare claims from 2011 to 2013. We assessed receipt of any HIV antiretrovirals or recommended combinations (ART), as defined by national care guidelines, and the source of payment. We identified predictors of antiretroviral use with risk‐adjusted generalized estimating equation logistic models. RESULTS All study persons living with HIV/AIDS in NHs had prescription drug coverage through Medicare's Part D program, and ART was 100% covered. However, only 63.9% received recommended ART, and 15.2% never received any antiretrovirals during their NH stay. The strongest predictor of not receiving antiretrovirals was the first 100 days of a long NH stay (odds ratio [OR] = .44; 95% confidence interval [CI] = .24‐.80). The strongest predictor of receiving recommended ART was health acuity (OR = 1.51; 95% CI = 1.20‐1.88). CONCLUSION People living with HIV in NHs do not always receive lifesaving ART, but the reasons are unclear and appear unrelated to economic barriers. J Am Geriatr Soc 68:777–782, 2020

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Section: Discussionmentioning

confidence: 99%

Economic Barriers to Antiretroviral Therapy in Nursing Homes

Olivieri‐Mui

Koethe

Briesacher

2019

J American Geriatrics Society

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“…The novel cytomegalovirus viral terminase inhibitor, letermovir, increased ATV AUC by over 200%, attributable to inhibition of OATP1B1/3 and CYP3A, and is expected to increase exposure to other statins too [188]. Several antiretroviral drugs increase statin exposure through inhibition of CYP3A and/or OATP1B1, including protease inhibitors (e.g., lopinavir, saquinavir, tipranavir) and pharmacokinetic enhancers (e.g., ritonavir, cobicistat) [189]. As stated above, CYP2C9 inhibitors (e.g., fluconazole) may interact with CYP2C9*2 or *3 carriage to increase FVT myotoxicity [105].…”

Section: Drug-statin Interactionsmentioning

confidence: 99%

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Turner

Pirmohamed

2019

JCM

141

126

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Statins are a cornerstone in the pharmacological prevention of cardiovascular disease. Although generally well tolerated, a small subset of patients experience statin-related myotoxicity (SRM). SRM is heterogeneous in presentation; phenotypes include the relatively more common myalgias, infrequent myopathies, and rare rhabdomyolysis. Very rarely, statins induce an anti-HMGCR positive immune-mediated necrotizing myopathy. Diagnosing SRM in clinical practice can be challenging, particularly for mild SRM that is frequently due to alternative aetiologies and the nocebo effect. Nevertheless, SRM can directly harm patients and lead to statin discontinuation/non-adherence, which increases the risk of cardiovascular events. Several factors increase systemic statin exposure and predispose to SRM, including advanced age, concomitant medications, and the nonsynonymous variant, rs4149056, in SLCO1B1, which encodes the hepatic sinusoidal transporter, OATP1B1. Increased exposure of skeletal muscle to statins increases the risk of mitochondrial dysfunction, calcium signalling disruption, reduced prenylation, atrogin-1 mediated atrophy and pro-apoptotic signalling. Rare variants in several metabolic myopathy genes including CACNA1S, CPT2, LPIN1, PYGM and RYR1 increase myopathy/rhabdomyolysis risk following statin exposure. The immune system is implicated in both conventional statin intolerance/myotoxicity via LILRB5 rs12975366, and a strong association exists between HLA-DRB1*11:01 and anti-HMGCR positive myopathy. Epigenetic factors (miR-499-5p, miR-145) have also been implicated in statin myotoxicity. SRM remains a challenge to the safe and effective use of statins, although consensus strategies to manage SRM have been proposed. Further research is required, including stringent phenotyping of mild SRM through N-of-1 trials coupled to systems pharmacology omics- approaches to identify novel risk factors and provide mechanistic insight.

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“…Although these results are limited by the fact that some statins interact with concurrent ART [133] while others interfere with metabolic control [134], collectively the data imply that by reducing both the procoagulant phenotype of monocytes and inflammation associated with the vascular endothelium (which may act as a substrate for clot formation), statins may reduce coagulation potential and hence the risk of CVD. To accurately answer that question, studies are now needed to evaluate whether the statin‐induced reduction of cardiovascular biomarkers will translate into a reduction in morbidity and mortality observed in PLHIV.…”

Section: Interventions To Target Immune Dysfunction and Inflammationmentioning

confidence: 99%

Managing HIV‐associated inflammation and ageing in the era of modern ART

et al. 2020

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Objectives This paper aims to address the concerns around ongoing immune activation, inflammation, and resistance in those ageing with HIV that represent current challenges for clinicians. Methods Presentations at a symposium addressing issues of ageing with HIV infection were reviewed and synthesised. Results The changing natural history and demographics of human immunodeficiency virus (HIV)‐infected individuals means new challenges in contemporary management. In the early years of the epidemic,management was focussed on acute, potentially life‐threatening AIDS‐related complications. From initial monotherapy with first‐generation antiretroviral therapy (ART), the development of combination highly active ART (HAART) allowed HIV control but ART toxicities, treatment adherence and drug resistance emerged as major issues. Today, the availability of potent and tolerable ART has made viral suppression achievable in most people living with HIV (PLHIV), and clinicians are confronted with managing a chronic condition among an ageing population. The combination of diseases of ageing and the co‐morbidities associated with HIV‐infection, even when well controlled, results in a complex set of challenges for many older PLHIV. There is a growing appreciation that many non‐AIDS‐related co‐morbidities are caused, at least in part, by persistent, low‐grade immune activation, inflammation, and hypercoagulability, despite suppressive ART. Conclusions In order to further improve HIV management, it is important to understand the enduring effects of chronically suppressed HIV infection, the potential contribution of these factors to the ageing process, the possibility of drug resistance, and the impact of different treatment strategies, including early ART initiation.

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Recommendations for Managing Drug–Drug Interactions with Statins and HIV Medications

Cited by 37 publications

References 46 publications

Economic Barriers to Antiretroviral Therapy in Nursing Homes

Economic Barriers to Antiretroviral Therapy in Nursing Homes

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Managing HIV‐associated inflammation and ageing in the era of modern ART

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