Determinants of HIV late presentation among men who have sex with men in Portugal (2014-2019): who's being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019.

Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.

Outbreak of Clostridium difficile PCR ribotype 027--the recent experience of a regional hospital.

BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, and several outbreaks with increased severity and mortality have been reported. In this study we report a C. difficile PCR ribotype 027 outbreak in Portugal, aiming to contribute to a better knowledge of the epidemiology of this agent in Europe. METHODS: Outbreak report with retrospective study of medical records and active surveillance data of all inpatients with the diagnosis of CDI, from 1st January to 31th December 2012, in a Portuguese hospital. C. difficile isolates were characterized regarding ribotype, toxin genes and moxifloxin resistance. Outbreak control measures were taken, concerning communication, education, reinforcement of infection control measures, optimization of diagnosis and treatment of CDI, and antibiotic stewardship. RESULTS: Fifty-three inpatients met the case definition of C. difficile-associated infection: 55% males, median age was 78.0 years (interquartile range: 71.0-86.0), 75% had co-morbidities, only 15% had a nonfatal condition, 68% had at least one criteria of severe disease at diagnosis, 89% received prior antibiotherapy, 79% of episodes were nosocomial. CDI rate peak was 13.89/10,000 bed days. Crude mortality rate at 6 months was 64.2% while CDI attributable cause was 11.3%. Worse outcome was related to older age (P = 0.022), severity criteria at diagnosis (leukocytosis (P = 0.008) and renal failure), and presence of fatal underlying condition (P = 0.025). PCR ribotype 027 was identified in 16 of 22 studied samples. CONCLUSIONS: This is the first report of a 027-CDI outbreak in Portugal. We emphasize the relevance of the measures taken to control the outbreak and highlight the importance of implementing a close and active surveillance of CDI.

Fungal meningitis in an immunocompetent patient.

Cryptococcal meningitis is a rare entity among immunocompetent hosts but, when it occurs, it is associated with significant morbidity and mortality. Clinical presentation as well as the course of the disease is usually subtle and indolent with headache and altered mental status. The authors present the case of a 59-year-old man, who sought medical help with a 2-week history of headaches accompanied by nausea and visual and hearing disturbances. On admission the patient was afebrile, presented visual and hearing deficits and had a normal magnetic resonance image of the brain. A lumbar puncture was performed and microscopic examination of the cerebrospinal fluid revealed yeasts that were identified as Cryptococcus spp. and later, by means of molecular biology techniques, as Cryptococcus neoformans, var. grubii. The patient was treated with liposomal amphotericin B plus fluconazole for 28 weeks. At follow-up after 1 year the patient was asymptomatic and received fluconazole 400 mg/day as prophylactic therapy. The outcome of Cryptococcus infections in immunocompetent hosts is reported to be poor as a result of a delayed diagnosis and suboptimal initial antifungal therapy. The influence of the normal immune response is unclear.

Mutations selected in HIV-2-infected patients failing a regimen including atazanavir.

OBJECTIVES: To investigate mutations selected in viruses from HIV-2-infected patients failing a highly active antiretroviral treatment (HAART) regimen including atazanavir/ritonavir. METHODS: Twenty-eight HIV-2-infected patients previously exposed to atazanavir/ritonavir and failing therapy were studied. The protease (PR) gene was amplified and sequenced, and mutations emerging under atazanavir/ritonavir selective pressure were reported. RESULTS: The I50L mutation emerged in 4 out of 28 HIV-2-infected patients failing a HAART regimen including atazanavir/ritonavir. Besides I50L, four PR mutations previously associated with protease inhibitor resistance (I54L, I64V, V71I and I82F) and six PR mutations of unknown impact (V10I, E37D, S43T, K45R, I75V and F85L) in HIV-2 were also identified in this small group of patients. CONCLUSIONS: Several mutations were associated with virological failure of a regimen including atazanavir/ritonavir in HIV-2-infected patients, including I50L for the first time. It should be included in HIV-2 algorithms for interpretation of genotypic resistance data, and taken into account when making therapeutic decisions for HIV-2-infected patients.

The demise of multidrug-resistant HIV-1: the national time trend in Portugal.

OBJECTIVES: Despite a decreasing mortality and morbidity in treated HIV-1 patients, highly active antiretroviral treatment (HAART) can still fail due to the development of drug resistance. Especially, multidrug-resistant viruses pose a threat to efficient therapy. We studied the changing prevalence of multidrug resistance (MDR) over time in a cohort of HIV-1-infected patients in Portugal. PATIENTS AND METHODS: We used data of 8065 HIV-1-infected patients followed from July 2001 up to April 2012 in 22 hospitals located in Portugal. MDR at a specific date of sampling was defined as no more than one fully active drug (excluding integrase and entry inhibitors) at that time authorized by the Portuguese National Authority of Medicines and Health Products (INFARMED), as interpreted with the Rega algorithm version 8.0.2. A generalized linear mixed model was used to study the time trend of the prevalence of MDR. RESULTS: We observed a statistically significant decrease in the prevalence of MDR over the last decade, from 6.9% (95% CI: 5.7-8.4) in 2001-03, 6.0% (95% CI: 4.9-7.2) in 2003-05, 3.7% (95% CI: 2.8-4.8) in 2005-07 and 1.6% (95% CI: 1.1-2.2) in 2007-09 down to 0.6% (95% CI: 0.3-0.9) in 2009-12 [OR=0.80 (95% CI: 0.75-0.86); P<0.001]. In July 2011 the last new case of MDR was seen. CONCLUSIONS: The prevalence of multidrug-resistant HIV-1 is decreasing over time in Portugal, reflecting the increasing efficiency of HAART and the availability of new drugs. Therefore, in designing a new drug, safety and practical aspects, e.g. less toxicity and ease of use, may need more attention than focusing mainly on efficacy against resistant strains.

[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.