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- Chronic hepatitis C treatment in HIV co-infection in Portugal: Results from a cohort OF 2133 patients presented by GEPCOI (Portuguese Coinfection Study Group)Publication . Miranda, AC; Mendez J, J; Serrão, R; Vale, F; Manata, MJ; Pinto, S; Gomes, A; Valente, C; Pacheco, P, et al.Direct-acting antiviral drugs (DAAs) have recently changed the paradigm of hepatitis C therapy, significantly improving treatment response rates, patient life expectancy and quality of life. In Portugal, sofosbuvir (SOF) and SOF/ledipasvir (SOF/LDV) were fully reimbursed by the National Health System since early 2015 and generalized use of interferon-free DAA based regimens became current practice. During 2016, the remaining DAAs were sequentially added and covered by the same health access policy. The Portuguese Study Group of Hepatitis and HIV Co-infection (GEPCOI) collected data from 15 clinical centres in Portugal, pertaining to the HCV treatment experience with DAA regimens. A cohort of 2133 patients was analysed, representing one of the largest DAA treated HCV/HIV co-infected individuals. The global sustained virologic response (SVR) achieved was 95% in this real-life cohort setting. Linear regression analysis showed significant differences in treatment response rates when using SOF plus ribavirin (RBV) combination in genotype 2 or 3 infected individuals (P < .002) and in those with liver cirrhosis (P < .002). These findings corroborate that early treatment is mandatory in HIV/HCV co-infected patients, as response rates may be negatively influenced by higher fibrosis stages and suboptimal DAA regimens. The current national Portuguese health policy should continue to promote wider treatment access and individualized therapy strategies, aiming at the elimination of HCV infection in this high-risk co-infected population
- Correction to: Clinical management of ageing people living with HIV in Europe: the view of the care providers.Publication . Boffito, M; Ryom, L; Spinner, C; Martinez, E; Behrens, G; Rockstroh, J; Hohenauer, J; Lacombe, K; Psichogyiou, M; Voith, N; Mallon, P; Branco, T, et al.
- Clinical management of ageing people living with HIV in Europe: the view of the care providersPublication . Boffito, M; Ryom, L; Spinner, C; Martinez, E; Behrens, G; Rockstroh, J; Hohenauer, J; Lacombe, K; Psichogyiou, M; Voith, N; Mallon, P; Branco, T, et al.BACKGROUND: Although guidelines for the management of HIV infection include recommendations for aging people living with HIV (PLWH), clinical practice of European HIV care providers may vary. METHOD: We performed a study using a 3-phase Delphi methodology by involving a panel of clinicians with expertise in HIV infection clinical management. The main aim of the study was to assess the care provider prospective on how HIV clinical care should be delivered to ageing PLWH. The first phase involved ten clinicians to identify HIV comorbidities of interest. The second and third phases recruited clinicians virtually via a web-based questionnaire that included 137 questions focussed on 11 comorbidities (e.g. cardiovascular disease, pulmonary disease, etc.). RESULTS: Results were analysed thematically and consensus (or not) among European physicians reported. Ninety-seven and 85 responses were collected in phase 2 and 3, respectively. High levels of agreement were found among clinical care providers across Europe and with the European AIDS Conference Society guidelines regarding key items of clinical management of comorbidities in ageing PLWH. CONCLUSION: However, we identified some important gaps, such as the lack of standardisation or implementation of the assessment of frailty or menopause, which are emerging as important factors to optimise ageing PLWH clinical care. Further studies are warranted to confirm whether intensified screening translates into HIV morbidity advances.
- Perceptions, Attitudes and Practices Towards Scabies in Communities on the Bijagós Islands, Guinea-BissauPublication . Lopes, MJ; Silva, E; Ca, J; Gonçalves, A; Rodrigues, A; Mandjuba, C, et al.Background: Scabies is highly endemic among impoverished populations and has been recently included in the WHO's list of neglected tropical diseases (NTDs). Community support and behavioural changes are essential for the success of control interventions. This study aimed to explore beliefs, prevention attitudes and healthcare-seeking behaviours towards scabies in the Bijagós Archipelago of Guinea-Bissau. Methods: Data were collected through two methods. Community key informants (community members, community health workers, healthcare workers and traditional healers) were interviewed using snowball sampling. A questionnaire covering perceptions, attitudes and practices was administered to community members using random cluster sampling. Thematic analysis of qualitative data was applied to identify themes. Descriptive statistics were used for quantitative data analysis. Results: There was a satisfactory awareness about scabies, but perceptions about disease causation and transmission were imprecise. Misconceptions about personal hygiene as the primary measure for scabies prevention were recurrent. Some participants recognised the importance of early treatment to interrupt transmission. Treatment of close contacts was not considered important. Costs were the main determining factor for treatment choice between traditional healer and the local health centre. Late presentation and delayed treatment were common and associated with poverty and stigmatisation. Scabies impaired quality of life by affecting social interactions, health, fitness to work and school attendance. Conclusions: There is a need to improve education, recognition, management and affordable access to treatment. Community education, healthcare workers' training and skin NTD integrated control programmes should address the challenges highlighted in this study.
- HIV-2 infection is associated with preserved GALT homeostasis and epithelial integrity despite ongoing mucosal viral replication.Publication . Fernandes, S; Pires, A; Matoso, P; Ferreira, C; Nunes-Cabaço, H; Correia, L; Valadas, E; Poças, J; Pacheco, P, et al.The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per μl) despite their undetectable viremia, accompanied by interferon-γ-producing CD8 T-cell expansion, irrespective of antiretroviral treatment. Nevertheless, there was no CD4 T-cell depletion, and Foxp3+ and IL-17- or IL-22-producing CD4 T-cell numbers were unaffected. Moreover, IL-22-producing innate lymphoid cells and IL-22-induced antimicrobial peptides and mucins were maintained. In agreement, the epithelium histology was preserved, including tight junction protein zonula occludens (ZO-1) levels. Furthermore, in vitro infection of colon epithelia with primary isolates revealed no HIV-2 impact on ZO-1 expression. Notably, sigmoid transcriptional levels of CCL20 and CCL28 were significantly increased, in direct correlation with GM-CSF, indicating a local response able to enhance CD4 T-cell recruitment. In conclusion, maintenance of mucosal integrity in HIV-2 infection was associated with T-cell recruitment responses, potentially counteracting CD4 T-cell depletion due to HIV-2 replication. These data have unique implications for the design of therapies targeting gut homeostasis in HIV-1 infection and other chronic inflammatory settings.
- Non-AIDS-related comorbidities in people living with HIV-1 aged 50 years and older: The AGING POSITIVE study.Publication . Serrão, R; Piñero, C; Velez, J; Coutinho, D; Maltez, F; Lino, S; Sarmento, E; Castro, R; Tavares, AP; Pacheco, P; Lopes, MJ; Mansinho, K; Miranda, AC; Neves, I; Abreu, R; Almeida, J; Pássaro, LOBJECTIVE: To characterize the profile of non-AIDS-related comorbidities (NARC) in the older HIV-1-infected population and to explore the factors associated with multiple NARC. METHODS: This was a multicentre, cross-sectional study including HIV-1-infected patients aged ≥50 years, who were virologically suppressed and had been on a stable antiretroviral therapy (ART) regimen for at least 6 months. A multiple regression model explored the association between demographic and clinical variables and the number of NARC. RESULTS: Overall, 401 patients were enrolled. The mean age of the patients was 59.3 years and 72.6% were male. The mean duration of HIV-1 infection was 12.0 years and the median exposure to ART was 10.0 years. The mean number of NARC was 2.1, and 34.7% of patients had three or more NARC. Hypercholesterolemia was the most frequent NARC (60.8%), followed by arterial hypertension (39.7%) and chronic depression/anxiety (23.9%). Arterial hypertension and diabetes mellitus were the most frequently treated NARC (95.6% and 92.6% of cases, respectively). The linear regression analysis showed a positive relationship between age and NARC (B=0.032, 95% confidence interval 0.015-0.049; p=0.0003) and between the duration of HIV-1 infection and NARC (B=0.039, 95% confidence interval 0.017-0.059; p=0.0005). CONCLUSIONS: A high prevalence of NARC was found, the most common being metabolic, cardiovascular, and psychological conditions. NARC rates were similar to those reported for the general population, suggesting a larger societal problem beyond HIV infection. A multidisciplinary approach is essential to reduce the burden of complex multi-morbid conditions in the HIV-1-infected population.
- Laterality of Pneumonia in Acute StrokePublication . Alves, P; Silva, C; Baptista, J; Lima, B; Jacinto, M; Trigueiros, F; Martins, A; Melo, T; Fonseca, ACBACKGROUND/AIMS: Previous studies demonstrated an alteration of diaphragmatic excursion on the paretic side after stroke; however, it is unclear if this change has clinical repercussions. We aimed to determine if there was an association between the paretic side and the laterality of pneumonia after stroke. METHODS: A retrospective analysis of a consecutive cohort of patients admitted to a stroke unit from 2008 to May 2016 was performed. Patients with the diagnosis of acute stroke and pneumonia were included. The laterality of pneumonia was determined through the blinded observation of chest X-rays. Fisher's exact test was applied to study the association between the side of paresis and pneumonia. RESULTS: One hundred and five patients were included. Sixty one percent (n = 64) had an ischemic stroke, 39% (n = 41) had brain hemorrhage, and 49.5% (n = 52) had right side paresis. We did not find in general an association between the side of paresis and the side of pneumonia (p = 1.00); however, we found a statistically significant association in patients with severe lower limb paresis (Medical Research Council, MRC ≤2; p = 0.035). CONCLUSION: We found an association between severe paresis of the lower limb (MRC ≤2) and ipsilateral pneumonia. We hypothesize that the proximity between the diaphragmatic and inferior limb corticospinal pathways could be the reason for this association.
- A case of Birt-Hogg-Dubé syndromePublication . Martins, L; Caixeiro, M; Costa, C; Feijó, S; Bárbara, C
- Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions.Publication . Marinho, A; Rodrigues, P; Caixas, U; Antunes, A; Branco, T; Hargivan, S; Marques, M; Monteiro, E; Pereira, SOBJECTIVES: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. METHODS: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. RESULTS: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. CONCLUSIONS: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity.
- Clinical experience in invasive fungal infectionsPublication . Pacheco, P; Ventura, A; Branco, T; Gonçalves, L; Carvalho, CLung infections caused by invasive filamentous fungi are very rare conditions in AIDS, but must be considered in patients with profound immune suppression especially in the presence of additional risk factors, such as hematologic malignancies, corticosteroid therapy, neutropenia, and chemotherapy. The authors report a case of dual lung infection caused by Aspergillus and Mucor, which occurred in a 34-year-old AIDS patient who was treated with chemotherapy for oral plasmablastic lymphoma. The case presented clinically with low grade fever and pulmonary cavitation, which suggested tuberculosis. After extensive investigation the diagnosis of mucormycosis was established and the patient was treated sequentially with liposomal amphotericin B and posaconazole. Despite a reduction in the size of the pulmonary cavitation, improvement of the lung interstitial infiltrates and clinical recovery, the patient was submitted to cardiothoracic surgery given the aggressive behavior of this invasive fungus. Histology of the surgical specimen showed numerous hyphae with a morphologic pattern compatible with Aspergillus as well as hyphae that were suggestive of Mucor.