Frequency and severity of potential drug interactions in a cohort of HIV-infected patients Identified through a Multidisciplinary team

Molas, Ema; Luque, Sònia; Retamero, A; Echeverría-Esnal, Daniel; Guelar, Ana; Montero, Milagro; Güerri, Roberto; Sorlí, Luisa; Lerma, Elisabet; Villar, Judith; Knobel, Hernando

doi:10.1080/15284336.2017.1404690

Cited by 22 publications

(25 citation statements)

References 21 publications

(9 reference statements)

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“… reported red DDIs mostly for nevirapine in combination with ketoconazole in their cohort in Uganda. Other studies in Switzerland and Spain reported mainly on red interactions between protease inhibitors/NNRTIs and central nervous system drugs or proton‐pump inhibitors . These drug categories were rarely prescribed in our cohort.…”

Section: Discussionmentioning

confidence: 82%

Prevalence and management of drug–drug interactions with antiretroviral treatment in 2069 people living with HIV in rural Tanzania: a prospective cohort study

et al. 2019

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Objectives Widespread access to antiretroviral therapy (ART) has substantially increased life expectancy in sub‐Saharan African countries. As a result, the rates of comorbidities and use of co‐medications among people living with HIV are increasing, necessitating a sound understanding of drug–drug interactions (DDIs). We aimed to assess the prevalence and management of DDIs with ART in a rural Tanzanian setting. Methods We included consenting HIV‐positive adults initiating ART in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) between January 2013 and December 2016. DDIs were classified using http://www.hiv-druginteractions.org as red (contra‐indicated), amber (potential clinical relevance requiring dosage adjustment/monitoring), yellow (weak clinical significance unlikely to require further management) or green (no interaction). We assessed management of amber DDIs by evaluating monitoring of laboratory or clinical parameters, or changes in drug dosages. Results Of 2069 participants, 1945 (94%) were prescribed at least one co‐medication during a median follow‐up of 1.8 years. Of these, 645 (33%) had at least one potentially clinically relevant DDI, with the highest grade being red in nine (< 1%) and amber in 636 (33%) participants. Of the 23 283 prescriptions, 19 (< 1%) and 1745 (7%) were classified as red and amber DDIs, respectively. Overall, 351 (2%) prescriptions were red DDIs or not appropriately managed amber DDIs. Conclusions Co‐medication use was common in this rural sub‐Saharan cohort. A third of participants had DDIs requiring further management. Of the 9% of participants with not appropriately managed DDIs, most were with cardiovascular and analgesic drugs. This highlights the importance of physicians’ awareness of DDIs for their recognition and management.

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Section: Discussionmentioning

confidence: 82%

Prevalence and management of drug–drug interactions with antiretroviral treatment in 2069 people living with HIV in rural Tanzania: a prospective cohort study

et al. 2019

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“…HIV/HCV coinfection, age, the prescribed antiretroviral regimen, and polypharmacy are independent risk factors for DDIs (45,46). It is therefore unsurprising that the prevalence of clinically relevant DDIs ranges from 14 to 41% (9,45,47).…”

Section: Discussionmentioning

confidence: 99%

Anti-HIV and Anti-Hepatitis C Virus Drugs Inhibit P-Glycoprotein Efflux Activity in Caco-2 Cells and Precision-Cut Rat and Human Intestinal Slices

Martinec

Huliciak

Štaud

et al. 2019

Antimicrob Agents Chemother

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P-glycoprotein (ABCB1), an ATP-binding-cassette efflux transporter, limits intestinal absorption of its substrates and is a common site of drug-drug interactions (DDIs). ABCB1 has been suggested to interact with many antivirals used to treat HIV and/or chronic hepatitis C virus (HCV) infections. Using bidirectional transport experiments in Caco-2 cells and a recently established ex vivo model of accumulation in precision-cut intestinal slices (PCIS) prepared from rat ileum or human jejunum, we evaluated the potential of anti-HIV and anti-HCV antivirals to inhibit intestinal ABCB1. Lopinavir, ritonavir, saquinavir, atazanavir, maraviroc, ledipasvir, and daclatasvir inhibited the efflux of a model ABCB1 substrate, rhodamine 123 (RHD123), in Caco-2 cells and rat-derived PCIS. Lopinavir, ritonavir, saquinavir, and atazanavir also significantly inhibited RHD123 efflux in human-derived PCIS, while possible interindividual variability was observed in the inhibition of intestinal ABCB1 by maraviroc, ledipasvir, and daclatasvir. Abacavir, zidovudine, tenofovir disoproxil fumarate, etravirine, and rilpivirine did not inhibit intestinal ABCB1. In conclusion, using recently established ex vivo methods for measuring drug accumulation in rat- and human-derived PCIS, we have demonstrated that some antivirals have a high potential for DDIs on intestinal ABCB1. Our data help clarify the molecular mechanisms responsible for reported increases in the bioavailability of ABCB1 substrates, including antivirals and drugs prescribed to treat comorbidity. These results could help guide the selection of combination pharmacotherapies and/or suitable dosing schemes for patients infected with HIV and/or HCV.

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“…Interaction between ARVs and concomitant medications has been reported at rates of 14-41% [3] . Drug-drug interaction is common in HIV-infected patients because these drugs act as drug metabolism enzyme inducers or inhibitors.…”

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confidence: 99%

“…Therefore, it is important to consider potential interactions to ensure effective viral suppression and minimal toxicity. It was reported that 70% of the 1.259 HIV-infected patients in Spain (from March 2015 to September 2016) used co-medications, and drug-drug interactions occured in 44.7% [3] . In this paper, we present the development of an unexpected drug-drug interaction in a patient starting ART and how it was managed.…”

mentioning

confidence: 99%

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HIV/AIDS Treatment is Easier But Drug-Drug Interactions?

Pullukçu¹,

Mermut²,

Yamazhan³

et al. 2019

mjima

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Frequency and severity of potential drug interactions in a cohort of HIV-infected patients Identified through a Multidisciplinary team

Abstract: Systematic evaluation detected a significant percentage of PDDIs requiring an intervention in HIV patients on ART. Monitoring and advice about drug-drug interactions should be part of routine practice.

Cited by 22 publications

References 21 publications

Prevalence and management of drug–drug interactions with antiretroviral treatment in 2069 people living with HIV in rural Tanzania: a prospective cohort study

Prevalence and management of drug–drug interactions with antiretroviral treatment in 2069 people living with HIV in rural Tanzania: a prospective cohort study

Anti-HIV and Anti-Hepatitis C Virus Drugs Inhibit P-Glycoprotein Efflux Activity in Caco-2 Cells and Precision-Cut Rat and Human Intestinal Slices

HIV/AIDS Treatment is Easier But Drug-Drug Interactions?

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