Assessing Prolongation of the Corrected QT Interval with Bedaquiline and Delamanid Coadministration to Predict the Cardiac Safety of Simplified Dosing Regimens.

Delamanid and bedaquiline are two drugs approved to treat drug-resistant tuberculosis, and each have been associated with corrected QT interval (QTc) prolongation. We aimed to investigate the relationships between the drugs' plasma concentrations and the prolongation of observed QT interval corrected using Fridericia's formula (QTcF) and to evaluate their combined effects on QTcF, using a model-based population approach. Furthermore, we predicted the safety profiles of once daily regimens.

QT effects of bedaquiline, delamanid, or both in patients with rifampicin-resistant tuberculosis: a phase 2, open-label, randomised, controlled trial.

Background: Bedaquiline and delamanid are the first drugs of new classes registered for tuberculosis treatment in 40 years. Each can prolong the QTc interval, with maximum effects occurring weeks after drug initiation. The cardiac safety and microbiological activity of these drugs when co-administered are not well-established.

Pharmacogenetic interactions between antiretroviral drugs and vaginally administered hormonal contraceptives.

Objective: In AIDS Clinical Trials Group study A5316, efavirenz lowered plasma concentrations of etonogestrel and ethinyl estradiol, given as a vaginal ring, while atazanavir/ritonavir increased etonogestrel and lowered ethinyl estradiol concentrations. We characterized the pharmacogenetics of these interactions.

Methods: In A5316, women with HIV enrolled into control (no antiretrovirals), efavirenz [600 mg daily with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)], and atazanavir/ritonavir (300/100 mg daily with NRTIs) groups.

Raltegravir pharmacokinetics before and during treatment with ombitasvir, paritaprevir/ritonavir plus dasabuvir in adults with human immunodeficiency virus-1 and hepatitis C virus coinfection: AIDS Clinical Trials Group sub-study A5334s.

Aims: AIDS Clinical Trials Group study A5334s evaluated the pharmacokinetics of raltegravir before and during combined administration of ombitasvir, paritaprevir/ritonavir, plus dasabuvir (OBV/PTV/r + DSV) and weight-based ribavirin in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected adults. The pharmacokinetics of OBV/PTV/r + DSV during raltegravir coadministration were also characterized.

Methods: Adults living with HIV/HCV coinfection receiving steady-state raltegravir (400 mg twice daily) with 2 nucleos(t)ide analogues were enrolled.

Antiretroviral therapy and vaginally administered contraceptive hormones: a three-arm, pharmacokinetic study.

Background: Drug-drug interactions between orally administered antiretroviral therapy (ART) and hormones released from an intravaginal ring are not known. We hypothesised that ART containing either efavirenz or ritonavir-boosted atazanavir would alter plasma concentrations of vaginally administered etonogestrel and ethinylestradiol but that ART concentrations would be unchanged during use of an intravaginal ring.

Methods: We did a parallel, three-group, pharmacokinetic evaluation at HIV clinics in Asia (two sites), South America (five), sub-Saharan Africa (three), and the USA (11) between Dec 30, 2014, and Sept 12, 2016.

The pharmacokinetics and pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected persons requiring hemodialysis.

Objective: To evaluate the pharmacokinetics and pharmacogenomics of efavirenz (EFV) and lopinavir/ritonavir (LPV/RTV) in HIV-infected persons requiring hemodialysis.

Design: Prospective, observational study of HIV-infected hemodialysis patients receiving one 600 mg tablet daily of EFV (N = 13) or three 133.3/33.

Effect of hydroxyurea and dideoxyinosine on intracellular 3'-deoxyadenosine-5'-triphosphate concentrations in HIV-infected patients.

Hydroxyurea (HU) significantly enhances the antiretroviral effects of the adenosine analog reverse transcriptase inhibitor dideoxyinosine (ddI). This is believed to be due to a reduction in intracellular de-oxyadenosine triphosphate (dATP) concentrations resulting from HU-mediated inhibition of ribonucleotide reductase (RnR). The effect of combined HU-ddI treatment on intracellular dATP pools in vivo has not been examined.