Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials

Background & AimsTelaprevir plus pegylated interferon/ribavirin (TPV+PegIFN/RBV) remains a therapeutic option for chronic hepatitis C virus (HCV) genotype (GT) 1 infection in many regions. We conducted two open-label, phase IIIb trials comparing safety and efficacy of all-oral ombitasvir/paritaprevir/ritonavir and dasabuvir±ribavirin (OBV/PTV/r+DSV±RBV) and TPV+PegIFN/RBV.MethodsTreatment-naïve (MALACHITE-I) or PegIFN/RBV-experienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r+DSV+weight-based RBV, OBV/PTV/r+DSV (treatment-naïve, GT1b-infected patients only), or 12weeks of TPV+PegIFN+weight-based RBV and 12–36 additional weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12weeks post-treatment (SVR12). Patient-reported outcome questionnaires evaluated mental and physical health during the studies.ResultsThree hundred eleven treatment-naïve and 148 treatment-experienced patients were randomized and dosed. Among treatment-naïve patients, SVR12 rates were 97% (67/69) and 82% (28/34), respectively, in OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV-treated GT1a-infected patients; SVR12 rates were 99% (83/84), 98% (81/83), and 78% (32/41) in OBV/PTV/r+DSV+RBV, OBV/PTV/r+DSV, and TPV+PegIFN/RBV-treated GT1b-infected patients. Among treatment-experienced patients, SVR12 rates were 99% (100/101) and 66% (31/47) with OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV. Mental and physical health were generally better with OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV. Rates of discontinuation due to adverse events (0–1% and 8–11%, respectively, p<0.05) and rates of hemoglobin decline to <10g/dl (0–4% and 34–47%, respectively, p<0.05) were lower for OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV.ConclusionsAmong non-cirrhotic, HCV GT1-infected patients, SVR12 rates were 97–99% with 12week, multi-targeted OBV/PTV/r+DSV±RBV regimens and 66–82% with 24–48 total weeks of TPV+PegIFN/RBV. OBV/PTV/r+DSV±RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events

Pro Libris: Lubuskie Pismo Literacko-Kulturalne, nr 4 (2010)

145 s. : il., portr.

Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: the MALACHITE-I/II trials

L

Psychosocial aspects of therapeutic management among HIV infected patients addicted to intravenous drugs

There are 13.2 million HIV infected persons addicted to intravenous drugs (AIDs) and 80% of them live to developing countries. Highly Active Antiretroviral Therapy (HAART) is provided to 15% of AIDs persons. Improper provision of HAART to AIDs persons was described both to Europe and to the USA. The factor which is responsible to HAART is adherence. The patients on substitutive treatment can achieve quite often the level of adherence and HAART effectiveness similar to persons not addicted to drugs. But not all addicted patients can follow medically advised treatment and live in good social position and that influences inappropriate results of provided support. Many investigators do confirm that there is no difference for activity of HIV infection to general population comparing to AIDs patients. Still there is some data that HAART can be provided to patients even in once daily mode. There are many infections which are influencing drug users history – i.e. tuberculosis, abscesses or STDs. About 95% of patients do suffer from HCV infection world wide. Adherence is very important to the treatment provided to drug users and sometimes drugs could be provided as Directly Observed Therapy – DOT. Antireroviral drugs thanks to the influence of cytochrome P450 (mainly CYP3A4) can develop interactions and should be properly medically adapted. Patients from the substitutive programs who are receiving antiretrovirals should be prepared for increased requirement of opioids and signs of the drugs deficiency to the patients.Na świecie zakażenie HIV u osób przyjmujących dożylne środki uzależniające (OPDŚU) może wynosić 13,2 mln osób, a 80% z nich żyje w krajach rozwijających się. Wysoce aktywną terapię antyretrowirusową (HAART) przyjmuje ok. 15% OPDŚU. Złe wykorzystanie HAART u OPDŚU zostało opisane zarówno w krajach europejskich jak i w USA. Czynnikiem, który warunkuje powodzenie terapii antyretrowirusowej jest adherencja. Pacjenci programów substytucyjnych często osiągają poziom adherencji i skuteczność HAART zbliżoną do uzyskiwanej u osób nigdy nieuzależnionych. Nie wszystkie osoby przyjmujące dożylne środki uzależniające mają możliwość stosować się do zaleceń terapeutycznych i mieć dobre warunki socjalno-ekonomiczne. Natomiast wiele badań wskazują, że HAART stosowane jeden raz dziennie jest równie efektywne, jak leczenie stosowane dwa razy dziennie. Większość badaczy zwraca uwagę na brak różnicy w postępie zakażenia HIV pomiędzy OPDŚU a osobami, które nabyły zakażenie w inny sposób. Znacznie częstsze jest występowanie chorób, które nie należą do schorzeń definiujących AIDS, natomiast w istotny sposób wpływają na losy narkomanów dożylnych zakażonych HIV. Ważnym elementem jest współzakażenie wirusem HCV, które może dotyczyć ponad 95% OPDŚU. U osób leczonych HAART sposobem na poprawienie adherencji jest tzw. leczenie bezpośrednio obserwowane – Directly Observed Therapy. Leki antyretrowirusowe poprzez wpływ na układ cytochromu P450 (głównie na CYP3A4) wchodzą w interakcje, które muszą być właściwie diagnozowane. Pacjenci programów substytucyjnych, u których wdraża się HAART z udziałem leków antyretrowirusowych powinni być przygotowani na wzrost zapotrzebowania na opioidy i ewentualne objawy niedoboru

A new calcium 2,5-dihydroxybenzoate: Synthesis, characterization and antioxidant studies and stress mediated cytotoxity in MCF-7 cells

The structure and composition of the calcium 2,5-dihydroxybenzoate (calcium gentisate) were studied by single-crystal and powder X-ray diffraction. Single-crystal X-ray analysis revealed that the compound crystallizes in the orthorhombic space group Pbcn. The Ca(II) cation is coordinated in a monodentate fashion by two symmetry-related gentisate anions and five water molecules. The metal ion and one of the water molecules are located on a 2-fold rotation axis. The adjacent monomeric units are assembled into a 3-D supramolecular framework via O–H…O hydrogen bonds. Comparison of the experimental powder pattern with that simulated from single-crystal X-ray data confirmed the purity and homogeneity of the sample. The FT-IR, UV/VIS, 1H and 13C NMR spectra of the calcium 2,5-dihydroxybenzoic acid were registered and analysed. Moreover the effect of calcium complex and 2,5-dihydroxybenzoic acid on basic oxidative stress parameters, such as thiol group content and lipid peroxidation in the human breast cancer cells MCF-7 was studied. The antiradical and ferric reducing power of these compounds was measured by DPPH, CUPRAC and FRAP methods. The chemical reactivity parameters (e.g. HOMO and LUMO orbitals, ionization potential, electron affinity) for Ca 2,5-dHB and 2,5-dHB were calculated at B3LYP/6-311++G∗∗ level of theory and discussed in relation to their antioxidant properties. Keywords: 2,5-Dihydroxybenzoic acid, Gentisic acid, 2,5-Dihydroxybenzoate, Calcium, Pro-/antioxidant, MCF-