230 research outputs found
L\u2019interruzione dell\u2019alimentazione e dell\u2019idratazione artificiali nei confronti di pazienti in stato vegetativo permanente: la prospettiva penalistica
Tutela dei diritti fondamentali e operazioni militari all\u2019estero : le sentenze Al-Skeini e Al-Jedda della Corte europea dei diritti umani
Investigation of ATP-metabolizing enzymes and purinergic receptors in a new in vitro blood-brain barrier model system
Efficacy and tolerability of multiple drug therapy in HIV-infected children
Objectives
To characterize the efficacy and tolerability of multiple drug therapy (MDT) among heavily pre-treated HIV-infected children.
Methods
An observational study of seven children treated with 4\u20137 antiretroviral agents. MDT regimens were chosen with regard to past antiretroviral exposure and genotypic resistance data. Five children received MDT once, one child twice and one child four times. All patients had AIDS and severe CD4+ depletion and failed >2 PI-based HAART regimens.
Results
Virologic response, defined as a 65log10 decrease in plasma HIV-1 RNA at week 24, was achieved in 7/11 MDT. Successful MDT kept a sustained viral suppression (<50 copies/ml) at longest follow-up (72\u201396 weeks). Successful MDT obtained a great immune recovery: the median rise in absolute and percentage of CD4+ cells was 261 and 4 at week 24 and it reached 480 and 16 at 72\u201396 weeks. Adverse events were common but generally manageable. Mild/moderate gastrointestinal complaints and laboratory abnormalities were detected in 5/11 and 8/11 MDT. Grade 2 severity pancreatitis occurred in one case with chronic active hepatitis C. Pancreatitis resolved within 30 days of MDT interruption.
Conclusions
MDT may be a therapeutic option in children who failed to respond to most standard HAART regimens
Does GSS Still Maintain Relevance on HAART Outcome After the Introduction of Newest Active Antiretroviral Drugs? 48 Weeks Results
Background: Since recent observations demonstrated that extended resistance to protease inhibitors, nucleosidic and non - nucleosidic retrotranscriptase inhibitors (PI, NRTI, NNRTI) is a marker of disease progression and death, it is a matter of the greatest importance that experienced human immunodeficiency virus (HIV) - infected patients with limited therapeutic options receive a suppressive therapy pending the availability of at least two new antiretroviral drugs. Aim of the present study is to evaluate if the GSS score, calculated by analyzing the resistance to historical antiretroviral drugs and drug classes, is still relevant since several new potent drugs and drug classes entered the current clinical use.
Methods: Taking into account patients without suppression of HIV replication for 65 6 months from October 2008 and October 2009, we analyzed viroimmunological and resistance data of 38 outpatients starting their last antiretroviral regimen including at least one of the following: maraviroc, enfuvirtide, raltegravir, etravirine, darunavir/ritonavir or tipranavir/ritonavir. Mutations present in all available genotypic resistance tests were recorded for each patient and then correlated to GSS value, assessed using the last genotypic ribonucleic acid (RNA) resistance test. GSS was studied as predictor of virological treatment outcome by univariate and multivariate logistic regression.
Results: At 48 weeks, undetectable viral load was obtained in 80% of patients without difference between GSS classes (HIV-RNA median 60% recurrence of specific mutations for NRTI: M41L, M184IV, L210W, T215FY, K219EQ and 75% for D67N. K103N and Y181CIV mutations for NNRTI persisted in 35% of cases and their prevalence incresed in parallel with the number of GRTs. About 60% of tests reported L10FIRVC, M36ILV, M46IL, I54VLAMTS, V82AFTSLI, and L90M mutations in the protease region. 63P mutation was found in a total number of GRTs close to 80%. This percentages, when correlated to GSS, revealed a distinct pattern for most mutations, that showed a greater prevalence for GSS = 2. Conversely, only NNRTI 181CIV and NRTI 210W showed larger numbers in GSS1 and GSS3.
Conclusions: Single drugs belonging to new antiretroviral classes did not correlate to viroimmunological success for any GSS. High frequency and recurrence over GRTs for specific mutations confirm their key role following the exposure to ARVs classes. A baseline HIV-RNA <50,000 cp/ml is a predictor of therapeutic success and a carefully selected HAART based upon the evaluation of GRTs can favorably influence the immunovirologic response
Evolution of the HIV-1 protease region in heavily pretreated HIV-1 infected patients receiving Atazanavir
Background: Previous in vitro studies indicated that Atazanavir (ATV) has a distinct resistance profile than other protease inhibitors (PIs). In treatment-experienced patients ATV resistance is characterised by the accumulation of at least four mutations among those that confer cross-resistance to the PIs. Objective: We studied the evolution of PIs resistance mutations in 10 HAART-failed patients undergoing ATV enrolled in an early access program. Study design: Virus genotypic resistance was determined from plasma collected at baseline and during treatment. HIV-RNA was extracted and the pol region amplified and sequenced. Genotypic data were used to determine drug susceptibility. Phylogenetic analysis was performed. Results: At baseline, genotypic data showed cross-resistance patterns to approved PIs in 6 patients. In two of these subjects new mutations (I54V and A71V) conferring cross-resistance emerged after 3 months of therapy. The I50L mutation was evidenced in one subject after 12 months of treatment. The "virtual" phenotype analysis mirrored the resistance profiles to ATV and other PIs and evidenced differences with tipranavir and darunavir. Conclusion: Genotype evolution within the protease region did not emerge at significant levels during salvage therapy of multidrug-experienced patients. ATV exhibited certain/same virologic effect on the majority of our patients
Riflessioni conclusive in tema di "diritto penale giurisprudenziale", "partecipazione" e "concorso esterno"
- …