HCV reinfection after HCV therapy among HIV/HCV-coinfected individuals in Europe.

OBJECTIVES: Although direct-acting antivirals (DAAs) can clear HCV in nearly all HIV/HCV-coinfected individuals, high rates of reinfection may hamper efforts to eliminate HCV in this population. We investigated reinfection after sustained virological response (SVR) in HIV/HCV-coinfected individuals in Europe. METHODS: Factors associated with odds of reinfection by 2 years after SVR in EuroSIDA participants with one or more HCV-RNA test and 2 years follow-up were assessed using logistic regression. RESULTS: Overall, 1022 individuals were included. The median age was 50 (interquartile range: 43-54 years), and most were male (78%), injection drug users (52%), and received interferon (IFN)-free DAAs (62%). By 24 months, 75 [7.3%, 95% confidence interval (CI): 5.7-8.9%] individuals were reinfected. Among individuals treated prior to 2014, 16.1% were reinfected compared with 4.2% and 8.3%, respectively, among those treated during or after 2014 with IFN-free and IFN-based therapy. After adjustment, individuals who had started treatment during or after 2014 with IFN-free or IFN-based therapy had significantly lower odds of reinfection (adjusted odds ratio = 0.21, 95% CI: 0.11-0.38; 0.43, 95% CI: 0.22-0.83) compared with those who had received therapy before 2014. There were no significant differences in odds of reinfection according to age, gender, European region, HIV transmission risk group or liver fibrosis. CONCLUSIONS: Among HIV/HCV-coinfected individuals in Europe, 7.3% were reinfected with HCV within 24 months of achieving SVR, with evidence suggesting that this is decreasing over time and with use of newer HCV regimens. Harm reduction to reduce reinfection and surveillance to detect early reinfection with an offer of treatment are essential to eliminate HCV.

Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients.

The ectodomain of gp41 is the target of potent binding and neutralizing antibodies (NAbs) and is being explored in new strategies for antibody-based HIV vaccines. Previous studies have suggested that the W164A-3S (3S) and EC26-2A4 (EC26) peptides located in the gp41 ectodomain may be potential HIV vaccine candidates. We assessed 3S- and EC26-specific binding antibody responses and related neutralizing activity in a large panel of chronic HIV-1-infected Portuguese individuals on ART. A similar proportion of participants had antibodies binding to 3S (9.6%) and EC26 (9.9%) peptides but the level of reactivity against 3S was significantly higher compared to EC26, except in the rare patients with double peptide reactivity. The higher antigenicity of 3S was unrelated with disease stage, as assessed by CD4+ T cell counts, but it was directly related with plasma viral load. Most patients that were tested (89.9%, N = 268) showed tier 1 neutralizing activity, the potency being inversely associated with plasma viral load. In the subset of patients that were tested for neutralization of tier 2 isolates, neutralization breadth was inversely correlated with plasma viral load and directly correlated with CD4+ T cell counts. These results are consistent with a role for neutralizing antibodies in controlling viral replication and preventing the decline of CD4+ T lymphocytes. Importantly, in patients with 3S-specific antibodies, neutralizing titers were inversely correlated with viral RNA levels and proviral DNA levels. Moreover, patients with 3S and/or EC26-specific antibodies showed a 1.9-fold higher tier 2 neutralization score than patients without antibodies suggesting that 3S and/or EC26-specific antibodies contribute to neutralization breadth and potency in HIV-1 infected patients. Overall, these results suggest that antibodies targeting the S3 and EC26 epitopes may contribute to reduce viral burden and provide further support for the inclusion of 3S and EC26 epitopes in HIV-1 vaccine candidates.

The prevalence and risk-factors of oral HPV DNA detection among HIV-infected men between men who have sex with men and heterosexual men.

BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal carcinomas are becoming more common with epidemiological impact on human immunodeficiency virus (HIV)- positive individuals. Objective: We evaluated prevalence and risk factors for oral HPV DNA among HIV-infected men who have sex with men (MSM) or heterosexual men. Methods: This cross-sectional hospital-based study included 255 HIV-infected men with different sexual orientation 142 MSM and 113 heterosexual men, who answered a self-administered questionnaire on sociodemographic, clinical and behavioural data. Oral swab and mouthwash samples were analysed by polymerase chain reaction and genotyped by AnyplexTM II 28 (Seegene®). Results: Oral HPV was detected in 17.6% (95% Confidence Interval (CI) 13.5-22.8%), 17.6% in MSM and 17.7% in heterosexual men (p = .984). Multiple HPV infections were detected in 86.7% of HPV-positive men. HPV 56 (13.7%) was the most prevalent high-risk genotype, HPV 66 (7.8%) and HPV 70 (12.3%) were the most prevalent probable HR and low-risk HPV genotypes (12.3% and 7.1%, respectively). At multivariable analysis models, oral HPV was associated with >100 lifetime sexual partners (Odds Ratio (OR) 3.73; 95% CI 1.42-9.77) or lifetime tongue-kissing partners (OR 3.20; 95% CI 1.22-8.39) and lower education level (OR 2.90; 95% CI 1.08-7.78 and 2.74; 95% CI 1.04-7.27, respectively). Conclusions: Oral HPV prevalence was similar between HIV-infected MSM and heterosexual men. Oral HPV was associated with lifetime sexual partners, lifetime tongue-kissing partners and being undergraduate, independently of sexual orientation.

CTX-M-15-producing uropathogenic Escherichia coli isolates at Rio de Janeiro, Brazil: Molecular epidemiology and MALDI-TOF MS.

Because of the high prevalence of CTX-M-15-producing Escherichia coli isolates causing urinary tract infections in Rio de Janeiro, we have investigated bla-CTX-M-15 gene presence, as well as CTX-M-15 production, in 32 E. coli isolates recovered from the urine of outpatients assisted at a public hospital located in the west zone of Rio. Molecular epidemiology was assessed by PFGE and phylo-typing methods. The work highlights the good performance of MALDI-TOF MS as an alternative tool to detect extended-spectrum beta-lactamases among CTX-M-15-producing E. coli isolates.

Serum Albumin as a Prognostic Marker for Serious Non-AIDS Endpoints in the Strategic Timing of Antiretroviral Treatment (START) Study.

Background: Serum albumin may be used to stratify human immunodeficiency virus (HIV)-infected persons with high CD4 count according to their risk of serious non-AIDS endpoints. Methods: Cox proportional hazards models were used to analyze the risk of serious non-AIDS events in the Strategic Timing of Antiretroviral Treatment (START) study (NCT00867048) with serum albumin as a fixed and time-updated predictor. Models with exclusion of events during initial follow-up years were built to assess the ability of serum albumin to predict beyond shorter periods of time. Secondarily, we considered hospitalizations and AIDS events. Results: Among 4576 participants, 71 developed a serious non-AIDS event, 788 were hospitalized, and 63 experienced an AIDS event. After adjusting for a range of variables associated with hypoalbuminemia, higher baseline serum albumin (per 1 g/dL) was associated with a decreased risk of serious non-AIDS events (hazard ratio, 0.37 [95% confidence interval, .20-.71]; P = .002). Similar results were obtained in a time-updated model, after controlling for interleukin 6, and after excluding initial follow-up years. Serum albumin was independently associated with hospitalization but not with risk of AIDS. Conclusions: A low serum albumin level is a predictor for short- and long-term serious non-AIDS events, and may be a useful marker of risk of noncommunicable diseases, particularly in resource-limited settings.

Hypovitaminosis D in HIV-infected patients in Lisbon: a link with antiretroviral treatment.

INTRODUCTION: Recent data indicates that low vitamin D (25(OH)D) levels can lead to a worst prognosis in HIV-infected individuals, even in those on successful antiretroviral therapy (ART) [1]. Portugal is the European country that has the largest average sun exposure time but prevalence of hypovitaminosis D is mostly unknown. Our aim was to determine the prevalence of hypovitaminosis D in HIV patients in Lisbon and the possible association with ART. METHODS: From 2012 to January 2014, plasma samples from 518 HIV-infected patients were collected to 25(OH)D levels determination. Data on demographic features (age, ethnicity, country of origin) and clinical/laboratory parameters were collected from clinical files (HIV subtype, CD4+ cell count, CD4+ nadir, viral load (VL), HBV/HCV co-infection and ART). 25(OH)D status was defined as: deficiency <20 ng/mL, insufficiency 20-30 ng/mL, optimal >30 ng/mL. RESULTS: Median age was 46 years old (±11); 62.0% (321/518) were male; 81.3% (421/518) were Caucasian and 78.6% (407/518) were Portuguese. Most patients (96.1%; 498/518), were HIV-1 infected, 22.9% (114/498) and 4.0% (20/498) of them were HCV and/or HBV co-infected, respectively. Mean CD4+ cell count was 648 cells/µL (±333) and nadir was 219 cells/µL (±179). On treated patients VL was <40 HIV RNA/mL in 86.7% (417/481). The median levels of 25(OH)D was 20.0 ng/mL (range 4.1-99.7) and we found differences between values observed during Winter (median 16.7 ng/mL) and Summer (median 24.9 ng/mL) (p<0.0001). Low 25(OH)D levels were not correlated to ethnicity (p=0.066). 25(OH)D level was <30 ng/mL in 80.1% (415/518) of the patients, from which 30.9% (160/518) and 49.2% (255/518) had insufficiency and deficiency levels, respectively. Most (92.9%; 481/518) were on ART: regimens containing PI (47.5%), NNRTI (40.3%; 41.3% on NVP and 58.7% on EFV), II (1.2%), PI+NNRTI (3.9%). Comparing the 25(OH)D level along the different ART regimens (PI vs NVP; PI vs EFV; PI vs no ART) there were differences between PI and EFV (p=0.044). CONCLUSIONS: In this study, 80.1% of the HIV-infected patients had hypovitaminosis D and ART regimens with EFV were more often associated with low 25(OH)D levels. Understanding the impact of the different antiretroviral drugs on 25(OH)D status could help to decide in clinical practice whether 25(OH)D supplementation or drug switch are the best options for each patient.

[Cognitive decline of medicamentous etiology]. / Declínio Cognitivo de Etiologia Medicamentosa.

In the elderly there is a high risk of inappropriate medication and adverse effects of polypharmacy. A 68 year-old female patient resorted to the Emergency Room for suspected stroke. According to the husband, in the six months prior to admission, she became progressively disorientated and dependent. She had resorted to various appointments from different specialties and was polymedicated. It was impossible to clarify the exact dosage. On neurological examination she presented disturbance in attention and memory, disorientation, constructional apraxia, myoclonus and gait imbalance. After the suspension of all chronic medication, she showed gradual improvement. By the time of discharge, her neurological examination was completely normal. Iatrogenic effect of drugs as a cause of reversible dementia should be considered. All patients, particularly the elderly and their caregivers, should be suitably informed about the drugs that are prescribed and the dosages used. Using the biopsychosocial model could prevent inappropriate polypharmacy and iatrogeny.

Nos doentes idosos há um risco elevado de medicação inapropriada e de efeitos adversos da polimedicação. Doente do sexo feminino, 68 anos, previamente autónoma, recorre ao Serviço de Urgência por suspeita de Acidente Vascular Cerebral. Segundo o marido, nos seis meses prévios à admissão, apresentou progressiva dependência funcional e períodos de desorientação. Por esse motivo, havia recorrido a consultas de diferentes especialidades, encontrando-se polimedicada, sendo impossível perceber a posologia administrada. Apresentava-se desatenta, desorientada, apráxica, com mioclonias e marcha atáxica. Durante o internamento, após suspensão de toda a medicação crónica, revelou melhoria gradual, apresentando, à data de alta, exame neurológico completamente normal. A iatrogenia medicamentosa como causa reversível para quadros demenciais deve ser equacionada. Todos os doentes, particularmente os idosos e seus cuidadores, deverão ser adequadamente informados acerca dos medicamentos prescritos e da respetiva posologia. A utilização do modelo biopsicossocial poderá evitar a polimedicação inapropriada e a iatrogenia.

[Monitoring antibiotic consumption in the surgery and orthopaedics]. / Monitorização do consumo de antibióticos: nos serviços de cirurgia e de ortopedia de seis hospitais SA.

Monitoring antibiotic consumption is a valuable tool which has been increasingly used in the last years due to the current concern with the emergence of resistant microbial strains. The present study aimed at monitoring antibiotic consumption, evaluating the economic impact of hospital antibiotic prescription and assessing the relationship between the prescribed antibiotics and the indications for either prophylactic or therapeutic use. This was a longitudinal pilot-study for which data were collected in six privately managed public hospital units during the month of May 2004, with a resulting sample of 1,122 admitted patients. We observed a prescription incidence rate of 76.9%, corresponding to a total of 1,154 dispensed antimicrobials, with a mean 71.2% of these antimicrobials being dispensed for the prophylaxis of surgical site infection (SSI). The mean cost of antibiotic courses was higher in cases of "suspected infection" (9.09 euro) or "confirmed infection" (8.74 euro) and lower in cases of "prophylaxis" (5.67 euro), a finding which is explained by the shorter mean duration of the later. There was a considerable variation among the different hospital units regarding the type of antibiotic compound that was used for SSI prophylaxis, with a mean duration of antibiotic use of 2.61 days for this indication and about half of the prophylactic regimens lasting longer than 24 hours, a fact that suggests an insufficient observation of the current recommendations for antibiotic use in SSI prophylaxis. This finding indicates the need for an investigation on the actual existence of local recommendations for SSI prophylaxis in individual hospital units and also for the evaluation of the compliance of practicing surgeons with eventually existing recommendations.