Switch from ritonavir-boosted to unboosted atazanavir guided by therapeutic drug monitoring

Plasma concentration of atazanavir (ATV) may be reduced when coadministered with tenofovir (TDF) or proton pump inhibitors. Boosting ATV exposure with ritonavir (r) may make it possible to overcome these drug interactions. However, jaundice and loss of the metabolic advantages of ATV are more frequent using ATV/r than ATV alone. Herein, we assessed whether therapeutic drug monitoring (TDM) could make it possible to identify the subset of patients in whom removal of ritonavir could be attempted without risk of suboptimal plasma ATV exposure and subsequent virological failure. A total of 56 patients with undetectable plasma HIV-RNA under a stable triple regimen containing ATV 300/100 mg qd were switched to ATV 400 mg qd. Plasma ATV concentrations were measured using a reliable high-performance liquid chromatography method. Median plasma ATV C(min) fell from 880 to 283 ng/ml (p = 0.03) after removal of ritonavir. While all patients on ATV/r showed ATV plasma concentrations within therapeutic values (IC(min) above 150 ng/ml) before switching, four patients (7%) fell below this threshold after switching to ATV 400 mg qd. However, only one of this group experienced virological failure at week 24 of follow-up. TDF was part of the antiretroviral regimen in all four cases. From a total of 29 (52%) patients on ATV/r showing grade 3-4 hyperbilirubinemia, only 7 (12%) remained on it upon switching to ATV 400 mg qd (p < 0.001). Patients with complete viral suppression under ATV/r 300/100 mg qd may benefit from switching to ATV 400 mg qd guided by TDM, which may make it possible to minimize adverse events without compromising antiviral efficacy in most cases.     

How should microbiology laboratories interpret cultures of the sonicate of closed needleless connectors?

IntroductionOur objective was to determine whether there is a cut-off in the needleless connectors’ (NCs) cultures that when combined with skin cultures it was as efficient as conventional superficial cultures to rule-out catheter colonization (CC) and catheter-related bloodstream infection (CRBSI).MethodsDuring 10 months, we collected samples and then we analyzed the validity values of skin + NCs cultures for CC and CRBSI considering the best cut-off showing at least >90% of specificity to have a high negative predictive value using a ROC curve.ResultsWe collected a total of 167 catheters. The optimal cut-off of NCs culture was 1000 cfu/NC. The validity values for CC and CRBSI combining skin cultures and NCs cultures using the selected cut-off were, respectively: S, 42.9%/16.7%; SP, 83.6%/75.8%; PPV, 27.3%/2.5%; and NPV, 91.0%/96.0%.ConclusionsThe combination of skin cultures and quantitative NCs cultures could be used for ruling-out CC and CRBSI.     

Cover Image,Volume 20, Issue 4

The cover image, by Inmaculada Ruz‐Maldonado et al., is based on the Original Article LH‐21 and abnormal cannabidiol improve β‐cell function in isolated human and mouse islets through GPR55‐dependent and ‐independent signalling, DOI: 10.1111/dom.13180 .

     

Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis

Joint destruction in rheumatoid arthritis (RA) is heritable, but knowledge on specific genetic determinants of joint damage in RA is limited. We have used the Immunochip array to examine whether genetic variants influence variation in joint damage in a cohort of Mexican Americans (MA) and European Americans (EA) with RA. We studied 720 MA and 424 EA patients with RA. Joint damage was quantified using a radiograph of both hands and wrists, scored using Sharp's technique. We conducted association analyses with the transformed Sharp score and the Immunochip single nucleotide polymorphism (SNP) data using PLINK. In MAs, 15 SNPs from chromosomes 1, 5, 9, 17 and 22 associated with joint damage yielded strong p‐values (p < 1 × 10^?4). The strongest association with joint damage was observed with rs7216796, an intronic SNP located in the MAP3K14 gene, on chromosome 17 (β ± SE = ?0.25 ± 0.05, p = 6.23 × 10^?6). In EAs, 28 SNPs from chromosomes 1, 4, 6, 9, and 21 showed associations with joint damage (p‐value < 1 × 10^?4). The best association was observed on chromosome 9 with rs59902911 (β ± SE = 0.86 ± 0.17, p = 1.01 × 10^?6), a synonymous SNP within the CARD9 gene. We also observed suggestive evidence for some loci influencing joint damage in MAs and EAs. We identified two novel independent loci (MAP3K14 and CARD9) strongly associated with joint damage in MAs and EAs and a few shared loci showing suggestive evidence for association.     

Chromatic-achromatic perimetry in four clinic cases: Glaucoma and diabetes

Background:Some diseases that affect the visual system may show loss of chromatic-achromatic sensitivity before obvious physical signs appear in the usual examination of the eye''s posterior segment. A perimetric study has been conducted with four typical patients with glaucoma and diabetes, at different stages of the disease.Results:The results seem to indicate losses in the achromatic-parvocellular perimetry and both chromatic perimetry tests, undetected by conventional SAP.Conclusions:Our results illustrate that our patients without visible retinal alterations show signs of suspicion in multichannel perimetry.     

Utility of pulmonary ultrasound to identify interstitial lung disease in patients with rheumatoid arthritis

Clinical Rheumatology - To analyze the diagnostic utility of lung ultrasound (US) to detect interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients comparing with high-resolution...     

Peripheral arterial disease in HIV patients older than 50 years of age

Our objective was to analyze the prevalence of peripheral arterial disease (PAD) in HIV patients at risk and to compare them with the general population. All HIV patients older than 50 years who attended our unit from October 2005-July 2006 and all persons attending for an annual medical checkup at an employees' insurance association during the same period were invited to participate in the study. Of the latter (n = 407), a person of the same sex and age (+/-5 years) was included for each HIV patient. PAD was assessed by the ankle-brachial index (ABI) in all subjects, and all completed the Edinburgh questionnaire. Ninety-nine HIV patients and 99 persons from the general population of the same age and sex were included in the study. The HIV patients had a greater prevalence of dyslipidemia, diabetes, and PAD, which was symptomatic in five of them and in one subject from the general population. Patients with HIV infection older than 50 had a high prevalence of PAD, and as it was asymptomatic in half the cases, an ABI may be performed in this population to actively look for PAD. Control of cardiovascular risk factors and the use of such drugs as platelet antiaggregation agents should therefore be optimized in this population.