A review of drug-drug interactions in older HIV-infected patients

Chary, Aarthi; Nguyen, Nancy; Maiton, Kimberly; Holodniy, Mark

doi:10.1080/17512433.2017.1377610

Cited by 22 publications

(36 citation statements)

References 164 publications

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“…Older HIV patients are more susceptible to faster progression of the disease, with shorter and less symptomatic stage [28]. The use of other medications for concomitant co-morbidities among older patients may result in drug-drug interaction which predisposes to ADR and also predisposes to greater risk of opportunistic infections [29]. However, aging is generally expected to be a marker for greater maturity, lifestyle stability, and disease-specific education capable of affecting long-term adherence to therapy [30].…”

Section: Discussionmentioning

confidence: 99%

Epidemiologic and viral predictors of antiretroviral drug resistance among persons living with HIV in a large treatment program in Nigeria

et al. 2020

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Background: Expanded access to combination antiretroviral therapy (cART) throughout sub-Saharan Africa over the last decade has remarkably improved the prognosis of persons living with HIV (PLWH). However, some PLWH experience virologic rebound after a period of viral suppression, usually followed by selection of drug resistant virus. Determining factors associated with drug resistance can inform patient management and healthcare policies, particularly in resource-limited settings where drug resistance testing is not routine. Methods: A case-control study was conducted using data captured from an electronic medical record in a large treatment program in Nigeria. Cases PLWH receiving cART who developed acquired drug resistance (ADR) and controls were those without ADR between 2004 and 2011. Each case was matched to up to 2 controls by sex, age, and education. Logistic regression was used estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with ADR. Results: We evaluated 159 cases with ADR and 299 controls without ADR. In a multivariate model, factors associated with ADR included older age (OR = 2.35 [age 30-40 years 95% CI 1.29, 4.27], age 41 + years OR = 2.31 [95% CI 1.11, 4.84], compared to age 17-30), higher education level (secondary OR 2.14 [95% CI 1.1.11-4.13]), compared to primary and tertiary), non-adherence to care (OR = 2.48 [95% CI 1.50-4.00]), longer treatment duration (OR = 1.80 [95% CI 1.37-2.35]), lower CD4 count((OR = 0.95 [95% CI 0.95-0.97]) and higher viral load (OR = 1.97 [95% CI 1.44-2.54]). Conclusions: Understanding these predictors may guide programs in developing interventions to identify patients at risk of developing ADR and implementing prevention strategies.

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Section: Discussionmentioning

confidence: 99%

Epidemiologic and viral predictors of antiretroviral drug resistance among persons living with HIV in a large treatment program in Nigeria

et al. 2020

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“…Regardless of SARS-CoV-2 infection, aging and co-morbidities are well recognised independent drivers of the development of drug–drug interactions (DDIs) [ 4 – 6 ]. Aging is associated with physiological changes that significantly affect the pharmacokinetics and pharmacodynamics of various drugs, thus increasing the risk of inappropriate dosing and the development of drug-related toxicity [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Drug–Drug Interactions and Prescription Appropriateness in Patients with COVID-19: A Retrospective Analysis from a Reference Hospital in Northern Italy

et al. 2020

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Background Patients hospitalised with severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2; coronavirus 2019 disease (COVID-19)] infection are frequently older with co-morbidities and receiving polypharmacy, all of which are known risk factors for drug–drug interactions (DDIs). The pharmacological burden may be further aggravated by the addition of treatments for COVID-19. Objective The aim of this study was to assess the risk of potential DDIs upon admission and during hospitalisation in patients with COVID-19 treated at our hospital. Methods We retrospectively analysed 502 patients with COVID-19 (mean age 61 ± 16 years, range 15–99) treated at our hospital with a proven diagnosis of SARS-CoV-2 infection hospitalised between 21 February and 30 April 2020 and treated with at least two drugs. Results Overall, 68% of our patients with COVID-19 were exposed to at least one potential DDI, and 55% were exposed to at least one potentially severe DDI. The proportion of patients experiencing potentially severe DDIs increased from 22% upon admission to 80% during hospitalisation. Furosemide, amiodarone and quetiapine were the main drivers of potentially severe DDIs upon admission, and hydroxychloroquine and particularly lopinavir/ritonavir were the main drivers during hospitalisation. The majority of potentially severe DDIs carried an increased risk of cardiotoxicity. No potentially severe DDIs were identified in relation to tocilizumab and remdesivir. Conclusions Among hospitalised patients with COVID-19, concomitant treatment with lopinavir/ritonavir and hydroxychloroquine led to a dramatic increase in the number of potentially severe DDIs. Given the high risk of cardiotoxicity and the scant and conflicting data concerning their efficacy in treating SARS-CoV-2 infection, the use of lopinavir/ritonavir and hydroxychloroquine in patients with COVID-19 with polypharmacy needs to be carefully considered.

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“…For first‐line ARV regimens, the most commonly implicated metabolic enzymes are the cytochrome P450s CYP3A, CYP2D6, and CYP2B6, and the UDP‐glucuronosyltransferase (UGT) subtypes UGT1A1, UGT1A3, and UGT1A9 . Affected ARV transporters include the efflux transporters P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP) and the uptake transporter organic anion transporting polypeptide (OATP) subtypes OATP1B1 and OATP1B3 . Inhibition of metabolic enzymes or efflux transporters by perpetrator drugs may lead to higher plasma and systemic concentrations of the victim ARV with an increased risk for adverse events.…”

Section: Interactions Within Arv Therapymentioning

confidence: 99%

“…Potential bidirectional interactions between sex steroid hormones and ARVs may occur through drug efflux or uptake transporters. Both ARVs and sex steroid hormones may influence drug transporter activity . The estrogens (estrone, estriol, and ethynyl estradiol) have been shown to induce P‐gp mRNA and protein expression by twofold to threefold and are subject to transport by P‐gp in cell culture systems .…”

Section: Arv Interactions With Hormone Therapymentioning

confidence: 99%

“…The majority of clinically relevant DDIs between ARVs and statins involve PIs and boosting agents (RTV and COBI) as perpetrators, as they are inhibitors of CYP3A4 . With concomitant boosting agents, systemic statin concentrations can increase by 2.6–3.9‐fold leading to increased risks of hepatotoxicity, myopathy, and rhabdomyolysis .…”

Section: Arv Interactions With Common Comorbiditiesmentioning

confidence: 99%

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Contemporary Drug–Drug Interactions in HIV Treatment

Devanathan

Anderson

Cottrell

et al. 2019

Clin Pharma and Therapeutics

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Despite development of modern antiretrovirals with lower drug interaction potential than their predecessors, drug interaction challenges remain. Standard treatment regimens still require multiple antiretrovirals that may cause, or may be the target of, drug interactions. Additionally, people living with HIV are living longer and often present with comorbid conditions that require concomitant long-term drug therapy. Also, treatment of infectious diseases in resource-limited settings can result in significant interactions. In this review, we describe absorption, distribution, metabolism, and excretion pathways as they relate to relevant drug interactions with antiretrovirals along with the potential clinical consequences of these interactions. We highlight clinical data that illustrate pertinent interactions and provide tools to assist in predicting drug interactions in the absence of clinical data. Given these tools and thoughtful consideration of drug combinations, drug therapy in people living with HIV can be safely and effectively managed throughout their lifetime.Understanding, predicting, and managing antiretroviral drugdrug interactions (DDIs) has traditionally been a challenge for both drug developers and clinicians treating people living with HIV (PLWH). Of more than 20 antiretrovirals developed to date, most are lipophilic in nature. Lipophilic compounds generally have higher cellular permeability and greater affinity for cytochrome P450 (CYP) drug-metabolizing enzymes and efflux drug transporters. Since these enzymes and transporters concentrate in the gastrointestinal tract and liver, most drug interactions occur at these sites. New antiretroviral (ARV) therapies bypassing CYP metabolism and drug transport have alleviated some drug interaction concerns but challenges remain. In particular, because PLWH are living longer due to effective ARV therapy, they are developing age-related comorbidities, with increasing DDI potential of polypharmacy for cardiovascular, endocrine, and oncologic disorders. In addition to bone marrow transplants for leukemia and lymphomas, the availability of solid organ transplant in PLWH can pose a DDI challenge with medications used to prevent rejection and prophylax against opportunistic infections. Finally, the introduction of new and novel ARV therapies may lag in resource-limited settings, where most of the burden of HIV exists and where other infections such as malaria and tuberculosis need to be treated or prophylaxed. This review highlights interactions between ARVs themselves and interactions between ARVs and common classes of concomitant medications. We review the relevant absorption, distribution, metabolism, and excretion pathways for these medications, the clinical consequences of administering concomitant medications with ARVs, key clinical examples of interactions where ARVs are affected by other drugs (otherwise known as the "victim" drug) or are the agent affecting concomitant drugs (otherwise known as the "perpetrator" drug), and investigate how ARV interactions...

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A review of drug-drug interactions in older HIV-infected patients

Cited by 22 publications

References 164 publications

Epidemiologic and viral predictors of antiretroviral drug resistance among persons living with HIV in a large treatment program in Nigeria

Epidemiologic and viral predictors of antiretroviral drug resistance among persons living with HIV in a large treatment program in Nigeria

Drug–Drug Interactions and Prescription Appropriateness in Patients with COVID-19: A Retrospective Analysis from a Reference Hospital in Northern Italy

Contemporary Drug–Drug Interactions in HIV Treatment

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