P95 Withdrawn P96 Clinically significant drug interactions among HIV-infected patients receiving antiretroviral therapy in outpatient HIV clinic

A major challenge in the management of antiretroviral therapy (ART) is to improve the patient’s adherence, reducing the burden caused by the high number of drugs that compose the treatment regimens for human immunodeficiency virus positive (HIV+) patients. Selection of the most appropriate treatment regimen is responsible for therapeutic success and aims to reduce viremia, increase the immune system response capacity, and reduce the incidence rate and intensity of adverse reactions. In general, protease inhibitor (PI) is one of the pillars of regimens, and darunavir (DRV), in particular, is frequently recommended, along with low doses of enzyme inhibitors as cobicistat (COBI) or ritonavir (RTV), by the international guidelines. The potential of clinically significant drug interactions in patients taking COBI or RTV is high due to the potent inhibitory effect on cytochrome CYP 450, which attracts significant changes in the pharmacokinetics of PIs. Regardless of the patient or type of virus, the combined regimens of DRV/COBI or DRV/RTV are available to clinicians, proving their effectiveness, with a major impact on HIV mortality/morbidity. This study presents current information on the pharmacokinetics, pharmacology, drug interactions, and adverse reactions of DRV; it not only compares the bioavailability, pharmacokinetic parameters, immunological and virological responses, but also the efficacy, advantages, and therapeutic disadvantages of DRV/COBI or DRV/RTV combinations.

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Drug-drug Interactions Among Thai Transgender Women Living with Human Immunodeficiency Undergoing Feminizing Hormone Therapy and Antiretroviral Therapy: The iFACT Study

Clinical Infectious Diseases ◽

10.1093/cid/ciaa038 ◽

2020 ◽

Cited By ~ 1

Author(s):

Akarin Hiransuthikul ◽

Linrada Himmad ◽

Stephen J Kerr ◽

Rena Janamnuaysook ◽

Theera Dalodom ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Confidence Interval ◽

Drug Interactions ◽

Hormone Therapy ◽

Geometric Mean ◽

Area Under The Curve ◽

Transgender Women ◽

Immunodeficiency Virus ◽

Clinically Significant ◽

Curve Maximum

Abstract Background Drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are a major concern among transgender women (TGW), which may lead to suboptimal ART adherence and inappropriate FHT dosage. To evaluate potential drug-drug interactions between FHT and ART, we performed intensive measurements of the pharmacokinetic (PK) parameters of blood tenofovir (TFV), efavirenz (EFV), and estradiol (E2). Methods Twenty TGW with newly diagnosed human immunodeficiency virus (HIV) infection were enrolled. FHT (E2 valerate 2 mg/d and cyproterone acetate 25 mg/d) was prescribed at baseline until week 5 and restarted at week 8. ART (TFV disoproxil fumarate/emtricitabine/EFV at 300/200/600 mg) was initiated at week 3. The E2 PK parameters were measured intensively at weeks 3 (without ART) and 5 (with ART), and TFV and EFV PK parameters were measured intensively at weeks 5 (with FHT) and 8 (without FHT). Results The median (interquartile range) age and body mass index were 25.5 (22.5–31.0) years and 20.6 (19.3–23.1) kg/m2, respectively. The differences in geometric mean ratios between weeks 3 and 5 were as follows for E2 area under the curve, maximum concentration, and concentration at 24 hours (C24), respectively: 0.72 (90% confidence interval, .64–.81; P < .001), 0.81 (.72–.92; P = .006), and 0.64 (.50–.83; P = .004). The differences in geometric mean ratios between weeks 5 and 8 were as follows for TFV AUC, TFV C24, and EFV C24: 0.86 (90% confidence interval, .80–.93; P = .002), 0.83 (.75–.93; P = .006), and 0.91 (.85–.97; P = .02). Conclusions Among HIV-positive TGW, E2 PK parameters were significantly lower in the presence of TFV disoproxil fumarate/emtricitabine/EFV, and some TFV and EFV PK parameters were lower in the presence of FHT. Further studies should determine whether these reductions are clinically significant and whether they occur with other FHT or ART regimens.

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Drug interactions: a review of the unseen danger of experimental COVID-19 therapies

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa340 ◽

2020 ◽

Vol 75 (12) ◽

pp. 3417-3424 ◽

Cited By ~ 1

Author(s):

Catherine Hodge ◽

Fiona Marra ◽

Catia Marzolini ◽

Alison Boyle ◽

Sara Gibbons ◽

...

Keyword(s):

Drug Interactions ◽

Herbal Medicines ◽

Qt Prolongation ◽

Critically Ill Patient ◽

Experimental Drugs ◽

Mesh Terms ◽

Experimental Therapies ◽

Clinically Significant ◽

Novel Coronavirus

Abstract As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug–drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for ‘COVID-19’, ‘2019-nCoV’, ‘2019 novel coronavirus’ and ‘SARS-CoV-2’. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms ‘COVID-19’, ‘Comorbidity’ and ‘Epidemiological Factors’. Potential drug–drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug–drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug–drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug–drug interaction resource to facilitate medication review for the critically ill patient.

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