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Background Anakinra, a recombinant human form of interleukin-1 receptor antagonist, is used to treat patients with active rheumatoid arthritis (RA). Objectives To report five patients with cutaneous adverse drug reactions due to anakinra and to evaluate the histopathological and immunohistochemical findings with the aim of understanding the possible mechanisms involved. Methods Five patients of a series of 10 patients with RA undergoing treatment with anakinra in a clinical trial presented inflammatory lesions at the anakinra injection sites. In each case, clinical features were recorded and skin biopsy specimens were obtained. In one patient sequential biopsy specimens were obtained from skin lesions at different stages of development. Tissue sections of the biopsy specimens were stained with haematoxylin and eosin and May-Grünwald-Giemsa, and were immunoreacted with antibodies to leucocyte common antigen, CD68, CD3, CD45RO, CD20 and CD45RA. Results The onset of reaction was within the first month of treatment and appeared as well-defined erythema and oedema involving the injection sites. In two patients the treatment had to be discontinued because of the skin reaction, and in one patient it was associated with systemic involvement. All biopsy specimens exhibited marked dermal oedema and a lichenoid dermal infiltrate composed mainly of lymphomononuclear cells with prominent populations of eosinophils and large CD68+ dermal macrophages and an increase in the number of mast cells, which were spindle shaped in a significant proportion. Conclusions Cutaneous toxicity is a frequent, usually well-tolerated complication of treatment with anakinra in patients with RA, although in some cases it can be associated with systemic involvement. The most relevant histopathological findings include dermal oedema and a lichenoid, perivascular and periadnexal predominantly lymphomononuclear infiltrate, with many eosinophils and the presence of enlarged CD68+ macrophages. These findings resemble those seen in skin reactions in patients receiving chemotherapy and colony-stimulating factors. We also found an increase in mast cell numbers that could be a specific effect of anakinra.

Background. The objective of this study was to quantify human immunodeficiency virus (HIV) type 1 RNA decay and dolutegravir (DTG) concentrations in the semen of HIV-infected patients receiving DTG-based first-line therapy.Methods. This was a prospective, single-arm, open-label study including 15 HIV-1-infected, antiretroviral therapy-naive men starting once-daily treatment with DTG (50 mg) plus abacavir-lamivudine (600/300 mg). HIV-1 RNA was measured in seminal plasma (SP) and blood plasma (BP) at baseline, on days 3, 7, and 14, and at weeks 4, 12, and 24. The HIV-1 RNA decay rate was assessed using nonlinear mixed-effects models. Total and free DTG concentrations were quantified 24 hours after the dose at weeks 4 and 24 by means of a validated liquid chromatography-tandem mass spectrometry method.Results. Viral decay was faster in BP than in SP in the first decay phase (half-life, 4.5 vs 8.6 days; P = .001) with no statistically significant differences in the second phase. HIV-1 RNA suppression (<40 copies/mL) was reached earlier in SP (4 vs 12 weeks; P = .008) due to lower baseline HIV-1 RNA levels. The median total DTG 24 hours after the dose in SP was 119.1 ng/mL (range, 27.2-377 ng/mL), which represents 7.8% of BP exposure. The median DTG free-fraction in SP was 48% of the total drug. Seminal protein-unbound DTG concentrations exceeded the in vitro 50% inhibitory concentration (0.21 ng/mL) by a median of 214-fold.Conclusions. DTG concentrations in SP are sufficient to contribute to rapid seminal HIV-1 RNA suppression.

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ObjectiveThe aim of the study was to investigate changes in plasma biomarkers of cardiovascular risk and lipids in a CD4-guided antiretroviral therapy interruption study. MethodsThis was a substudy of a prospective, randomized, multicentre treatment interruption study. At months 12, 24 and 36, monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), interleukin-8 (IL-8), soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin), and tissue plasminogen activator (t-PA) were measured using a multiplex cytometric bead-based assay. Total cholesterol (total-c), high-density lipoprotein cholesterol (HDL-c) and triglycerides (TG) were determined using standard methods. ResultsFifty-four patients were included in the study [34 in the treatment continuation (TC) arm and 20 in the treatment interruption (TI) arm]. There were no differences at baseline between the groups, except in CD4 cell count, which was higher in the TI arm (P = 0.026), and MCP-1, which was higher in the TC arm (P = 0.039). MCP-1 and sVCAM-1 were increased relative to baseline at the three study time-points in the TI arm, with no changes in the TC arm. Soluble CD40L and sP-selectin were increased at month 36 in both arms, with a greater increase in the TI arm (P = 0.02). t-PA was increased in both arms at the three time-points. Total-c, HDL-c and low-density lipoprotein cholesterol (LDL-c) were decreased in the TI arm at the three time-points, with no changes in the total-c/HDL-c ratio. HIV viral load positively correlated with MCP-1 at months 12 and 24. Regression analysis showed a significant negative association of HDL-c with MCP-1 and sVCAM-1. ConclusionsA significant increase in cardiovascular risk biomarkers persisting over the prolonged study period was seen in the TI arm. This factor may contribute to the increased cardiovascular risk observed in previous studies.

Etravirine achieves concentrations several times greater than the IC(50) range in CSF. All patients with undetectable plasma viral load were virologically suppressed in CSF while receiving an etravirine-containing regimen. Etravirine may help in controlling HIV-1 in CNS.

BackgroundColonization by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has been found to be markedly more common in HIV-infected individuals in the USA. Studies evaluating the prevalence MRSA colonization in HIV-infected populations in Europe are scarce. The aim of this study was to investigate the prevalence of MRSA colonization in a cohort of HIV-infected patients in Barcelona, Spain.MethodsNasal and pharyngeal S. aureus carriage was assessed in a random sample of 190 patients from an outpatient HIV clinic. Nasal and pharyngeal swab specimens were obtained for staphylococcal culture from 190 and 110 patients respectively. All MRSA isolates were screened for Panton-Valentine leukocidin (PVL) genes by PCR. Molecular characterization of MRSA isolates was performed by multilocus sequence typing. Data related to HIV infection, healthcare exposure, and previously described risk factors for MRSA were collected from medical records and a questionnaire administered to each patient.ResultsThe patients’ characteristics were as follows: male, 83 %; median (IQR) age, 45 (39–49) years; intravenous drug users, 39 %; men who have sex with men, 32 %; heterosexual, 26 %; CD4 count, 528/μL (IQR 351–740); on antiretroviral therapy, 96 %; and undetectable plasma viral load, 80 %. Sixty-five patients (34 %) were colonized by S. aureus. MRSA colonization was found in 1 % and 2 % of nasal and pharyngeal samples respectively. No PVL positive MRSA strains were detected and all the MRSA isolates belonged to typical hospital-acquired clones.ConclusionsOur data suggest that CA-MRSA colonization is not currently a problem in HIV-infected individuals in our area.

In this small pilot study, LPV/r monotherapy OD maintained plasma HIV RNA suppression at 48 weeks in most patients, with no cases of CSF viral escape. However, CSF LPV concentrations were close to the 50% inhibitory concentration threshold in several patients; hence, this intervention should be avoided in patients with advanced immune suppression and/or those individuals presenting with significant comorbidities such as hepatitis C coinfection.